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Sample records for bovine mammary gland

  1. The major bovine mastitis pathogens have different cell tropisms in cultures of bovine mammary gland cells

    NARCIS (Netherlands)

    Lammers, A.; Vorstenbosch, van C.J.; Erkens, J.H.F.; Smith, H.E.

    2001-01-01

    We previously showed that Staphylococcus aureus cells adhered mainly to an elongated cell type, present in cultures of bovine mammary gland cells. Moreover. we showed that this adhesion was mediated by binding to fibronectin. The same in vitro model was used here, to study adhesion of other

  2. Genomic study of the mammary gland in bovines acclimated to a ...

    African Journals Online (AJOL)

    Mammary gland tissue was used for transcriptomic studies. Prolactin and GH plasmatic ... From the 4608 transcripts in the BLO-Bovine EST (Michigan State University, US) databank that were used in this experiment, 105 differentially expressed genes were identified in at least one of the groups. Among these, the authors ...

  3. Effect of Staphylococcus aureus and Streptococcus uberis on apoptosis of bovine mammary gland lymphocytes.

    Science.gov (United States)

    Slama, Petr; Sladek, Zbysek; Rysanek, Dusan; Langrova, Tereza

    2009-10-01

    The aim of this study was to determine whether lymphocyte apoptosis is modulated by infections caused by Staphylococcus aureus and Streptococcus uberis. Samples of cell populations were obtained by lavage of the mammary glands at 4 intervals (24, 48, 72 and 168 h) following infection. The percentage of apoptotic lymphocytes peaked at 168 h after challenge with S. aureus or S. uberis. Subsequent experiments focused on in vitro cultivation of mammary gland lymphocytes with S. aureus and S. uberis. These experiments showed a lower percentage of apoptotic lymphocytes following 3h of cultivating cells with bacteria than after cultivation without bacteria. The results demonstrate that during both experimental infection of bovine mammary glands with S. aureus or S. uberis and during in vitro cultivation of lymphocytes with S. aureus or S. uberis, apoptosis of lymphocytes is delayed.

  4. The antiproliferative effect of bovine lactoferrin on canine mammary gland tumor cells.

    Science.gov (United States)

    Yamada, Yuichi; Sato, Reeko; Kobayashi, Saori; Hankanga, Careen; Inanami, Osamu; Kuwabara, Mikinori; Momota, Yutaka; Tomizawa, Nobuyuki; Yasuda, Jun

    2008-05-01

    Lactoferrin has several biological activities, including antitumor activities in some human and animal tumor cells. Clinical trials have been carried out in human medicine based on these effects. However, the antitumor effects of lactoferrin in veterinary medicine remain unknown. In this in vitro study, we demonstrated that co-incubation of canine mammary gland tumor cells (CIPp and CHMp) and bovine lactoferrin induced growth arrest of tumor cells. This growth arrest was associated with induction of G1 arrest. Furthermore, this effect was stronger in tumor cells than in normal cells. These findings demonstrate that bovine lactoferrin has anti-tumor activity in canine mammary tumors and has the potential for use in tumor-bearing dogs.

  5. Effects of increased milking frequency on gene expression in the bovine mammary gland

    Directory of Open Access Journals (Sweden)

    Sonstegard Tad S

    2008-07-01

    Full Text Available Abstract Background Previous research has demonstrated that increased milking frequency of dairy cattle during the first few weeks of lactation enhances milk yield, and that the effect persists throughout the entire lactation period. The specific mechanisms controlling this increase in milk production are unknown, but suggested pathways include increased mammary epithelial cell number, secretory capacity, and sensitivity to lactogenic hormones. We used serial analysis of gene expression (SAGE and microarray analysis to identify changes in gene expression in the bovine mammary gland in response to 4× daily milking beginning at d 4 of lactation (IMF4 relative to glands milked 2× daily (Control to gain insight into physiological changes occurring within the gland during more frequent milking. Results Results indicated changes in gene expression related to cell proliferation and differentiation, extracellular matrix (ECM remodeling, metabolism, nutrient transport, and immune function in IMF4 versus Control cows. In addition, pathways expected to promote neovascularization within the gland appeared to be up regulated in IMF4 cows. To validate this finding, immunolocalization of Von Willebrandt's factor (VWF, an endothelial cell marker, and its co-localization with the nuclear proliferation antigen Ki67 were evaluated in mammary tissue sections at approximately d 7 and d 14 of lactation in cows milked 4× daily versus Controls to estimate endothelial cell abundance and proliferation within the gland. Consistent with expression of genes related to neovascularization, both abundance of VWF and its co-localization with Ki67 appeared to be elevated in cows milked 4× daily, suggesting persistent increased milk yield in response to increased milking frequency may be mediated or complemented by enhanced mammary ECM remodeling and neovascularization within the gland. Conclusion Additional study is needed to determine whether changes in ECM remodeling and

  6. Morphologic observation of neutrophil diapedesis across bovine mammary gland epithelium in vitro.

    Science.gov (United States)

    Lin, Y; Xia, L; Turner, J D; Zhao, X

    1995-02-01

    Neutrophils are present in milk of cows as a means of suppressing invading pathogens during mastitis. However, the manner by which neutrophils traverse the secretory epithelia is still not clear: do they diapedese between epithelial cells or do they kill epithelial cells to gain entry into milk? We investigated the process of bovine neutrophil diapedesis across bovine mammary gland epithelium in vitro. The bovine mammary epithelial cell line MAC-T, grown on collagen-coated filters, formed a confluent monolayer with characteristic tight junctions, basal-apical polarity, and functional barriers to the dye trypan blue. Neutrophils added on the apical surface of the monolayer were stimulated to diapedese across the epithelium by the addition of Staphylococcus aureus (10(7) colony-forming units/ml) to the basal compartment. Light and transmission electron microscopy revealed the series of events for neutrophil transmigration: accumulation of neutrophils on the surface of epithelial monolayer; projection of pseudopods into intercellular junctions and movement of neutrophils between adjacent epithelial cells; and reapproximation of the lateral epithelial cell membranes and reformation of the apical tight junctions after neutrophils crossed the epithelium. Morphologically, epithelial cell damage caused by neutrophil diapedesis was not evident. This in vitro model provides a two-dimensional epithelial sheet by which neutrophil diapedesis can be qualitatively studied under defined conditions. Results of the study suggest a major mode by which bovine neutrophils diapedese across the alveolar epithelia into milk during mastitis.

  7. Development and validation of a dedicated microarray for the evaluation of bovine mammary gland health status and milk quality.

    Science.gov (United States)

    Broccolo, Francesco; Maran, Valentina; Oggioni, Massimo; Matteoli, Barbara; Greppi, Gianfranco; Ceccherini-Nelli, Luca; Fusetti, Lisa

    2013-07-01

    The purpose of this study was the output and set up of the milk array, a dedicated array designed to investigate the expression levels of many genes involved in cow mammary gland inflammation and milk production regulation. First, a new targeted genes panel was selected. Successively, the microarray reliability was examined by yellow and dye swap experiments using the normal and mastitic mammary gland samples from the same cow. The sensitivity and reliability were evaluated using different amounts of the same mastitic mammary gland RNA: a good linear regression (R (2) = 0.758) was obtained also using only 3 μg of RNA. We used both reverse transcriptase RT-qPCR and the microarray to analyze 100 bovine genes (96 known to be involved in inflammation and milk production regulation and four housekeeping genes) in pooled total RNA isolated from tissue samples. All genes were detectable by RT-qPCR and microarray: a good mean correlation coefficient over all samples of 0.885 showed that both methods were similarly well suited to analyze gene expression in these samples. This report describes the development of small DNA microarray of fully defined genes suitable for analysis of expression of many genes involved in cow mammary gland inflammation and milk production regulation; this platform will prove useful as diagnostic tool prototype to perform a more in-depth analysis of the milk quality and mammary glands health status.

  8. Primary cilia distribution and orientation during involution of the bovine mammary gland.

    Science.gov (United States)

    Biet, J; Poole, C A; Stelwagen, K; Margerison, J K; Singh, K

    2016-05-01

    The regulation of mammary gland involution occurs through multiple levels including environmental factors, hormones, and local intramammary signals. Primary cilia (PC) are signaling organelles that sense biochemical and biophysical extracellular stimuli and are vital for cellular and tissue function. The aim of this study was to examine the distribution, incidence, and orientation of PC. Furthermore, we determined changes in expression levels of the signal transducer and activator of transcription (STAT)6 at the onset of bovine mammary gland involution. Mammary tissue was collected from pasture-fed, primiparous, nonpregnant Friesian dairy cows at mid lactation (n=5 per group) killed 6-h after milking (lactating controls) and during involution after 7 and 28 d of nonmilking (NM). Fluorescent immunohistochemistry and confocal microscopy of tissue sections showed that PC were present on luminal secretory epithelial cells (SEC), myoepithelial cells (MEC), and stromal fibroblast cells (SFC). Furthermore, in all 3 experimental groups, different PC positions or orientations relative to the cell surface were identified on SEC and MEC, which projected toward the lumen and were either straight, bent, or deflected against the apical cell surface, whereas PC in SFC were confined to the interalveolar space. However, by 28-d NM, fewer PC projected into the luminal space and most appeared deflected or projected toward the interalveolar space. Furthermore, by 28-d NM, with the increase in stromal connective tissue, more PC were detected within the interalveolar and interlobular stroma. At 28-d NM, we observed a decrease in luminal cilia relative to the total number of cilia. The number of ciliated cells in the total fraction (SEC, MEC, and SFC) was the same for all 3 groups, although in the luminal fraction (SEC and MEC), PC per nuclei increased by 28-d NM relative to lactation. At all 3 stages, we detected variations in shape and orientation of PC within the same alveolus, with

  9. Quantitative proteome analysis of bovine mammary gland reveals protein dynamic changes involved in peak and late lactation stages.

    Science.gov (United States)

    Zheng, Xianrui; Ning, Chao; Dong, Yichun; Zhao, Pengju; Li, Junhui; Fan, Ziyao; Li, Jiang; Yu, Ying; Mrode, Raphael; Liu, Jian-Feng

    2017-12-09

    Mammary gland is an important organ for milk synthesis and secretion. It undergoes dramatic physiological changes to adapt the shift from peak to late lactation stage. Protein plays a final very vital role in many life functions, and the protein changes during different lactation stages potentially reflect the biology of lactation and the functions of mammary gland in cows. In current study, we adopted tandem mass tags label-based quantitative analysis technique and to investigate proteome changes occurring in bovine mammary gland from peak to late lactation stages. A total of 3753 proteins from mammary tissues taken at two lactation points from four individual cows by biopsy were quantified, out of which 179 proteins were expressed differentially between two stages. We observed five new DEPs (AACS, DHCR7, GSTM3, SFRP1 and SFRP4) and nine functional well-studies known proteins (PLIN2, LPIN1, PLIN3, GSN, CD74, MMP2, SOD1, SOD3 and GPX3) related to milk performance and mammary morphology. Bioinformatics analyses of the DEPs showed a majority of the up-regulated proteins during late lactation stage were related to apoptosis and immune process, while the downregulated proteins were mainly involved in localization, lipid metabolic and transport process. This suggests that the mammary gland can adapt to different molecular functions according to the biological need of the animal. From the integrated analysis of the differentially expressed proteins with known quantitative trait loci and genome-wide association study data, we identified 95 proteins may potentially affect milking performance. We expect findings in this study could be a valuable resource for future studies investigating the bovine proteome and functional studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Genomic study of the mammary gland in bovines acclimated to a ...

    African Journals Online (AJOL)

    Daniela

    2016-02-06

    Feb 6, 2016 ... The marked DNA hybridization solution - which integrated 40 µL probe mix, 2 µL polyA DNA (Sigma,. 10 mg/mL), 2 µL of 50x .... metabolism and cellular communication, including the synthesis of milk protein and mammary gland stress adaptation ..... Toll-like receptors 2 and 4, and acute phase cytokine.

  11. Expression and localisation of oestrogen and progesterone receptors in the bovine mammary gland during development, function and involution.

    Science.gov (United States)

    Schams, D; Kohlenberg, S; Amselgruber, W; Berisha, B; Pfaffl, M W; Sinowatz, F

    2003-05-01

    It is now well established that oestrogen and progesterone are absolutely essential for mammary gland development. Lactation can be induced in non-pregnant animals by sex steroid hormone treatment. Most of the genomic actions of oestrogens are mediated by two oestrogen receptors (ER)-alpha and ERbeta, and for gestagens in ruminants by the progesterone receptor (PR). Our aim was the evaluation of mRNA expression and protein (localisation and Western blotting) during mammogenesis, lactogenesis, galactopoiesis (early, middle and late) and involution (8, 24, 28, 96-108 h and 14-28 days after the end of milking) in the bovine mammary gland (total no. 53). During these stages, the mRNA was assessed by means of real-time RT-PCR (LightCycler). The protein for ERalpha, ERbeta and PR was localised by immunohistochemistry and Western blotting. The mRNA expression results indicated the existence of ERalpha, ERbeta and PR in bovine mammary gland. Both ERalpha and PR are expressed in fg/ micro g total RNA range. The highest mRNA expression was found for ERalpha and PR in the tIssue of non-pregnant heifers, followed by a significant decrease to a lower level at the time of lactogenesis with low concentrations remaining during lactation and the first 4 weeks of involution. In contrast, the expression of ERbeta was about 1000-fold lower (ag/ micro g total RNA) and showed no clear difference during the stages examined, with a significant increase only 2-4 weeks after the end of milking. Immunolocalisation for ERalpha revealed a strong positive staining in nuclei of lactocytes in non-pregnant heifers, became undetectable during pregnancy, lactogenesis and lactation, and was again detectable 14-28 days after the end of milking. In contrast, PR was localised in the nuclei of epithelial cells in the mammary tIssue of non-pregnant heifers, in primigravid animals, and during late lactation and involution. During lactogenesis, peak and mid lactation, fewer nuclei of epithelial cells were

  12. Comparative glycolysis and Krebs cycle metabolism of the bovine and murine mammary gland determined with [13C6] glucose and mass spectrometry

    Science.gov (United States)

    The compositions of bovine and murine milk differ significantly with respect to the proportions of lactose, protein, and fat. To better understand the metabolic origins of this difference, we interrogated the crossroads of glycolysis and the Krebs cycle in the mammary gland of cows and mice using a ...

  13. Mammary gland stem cells

    DEFF Research Database (Denmark)

    Fridriksdottir, Agla J R; Petersen, Ole W; Rønnov-Jessen, Lone

    2011-01-01

    Distinct subsets of cells, including cells with stem cell-like properties, have been proposed to exist in normal human breast epithelium and breast carcinomas. The cellular origins of epithelial cells contributing to gland development, tissue homeostasis and cancer are, however, still poorly...... and differences between mouse and human gland development with particular emphasis on the identity and localization of stem cells, and the influence of the surrounding microenvironment. It is concluded that while recent advances in the field have contributed immense insight into how the normal mammary gland...... develops and is maintained, significant discrepancies exist between the mouse and human gland which should be taken into consideration in current and future models of mammary stem cell biology....

  14. Proteomic Analysis Reveals PGAM1 Altering cis-9, trans-11 Conjugated Linoleic Acid Synthesis in Bovine Mammary Gland.

    Science.gov (United States)

    Wang, T; Lee, S B; Hwang, J H; Lim, J N; Jung, U S; Kim, M J; Kang, H S; Choi, S H; Lee, J S; Roh, S G; Lee, H G

    2015-05-01

    cis-9, trans-11 Conjugated linoleic acid (CLA) is one of the most extensively studied CLA isomers due to its multiple isomer-specific effects. However, the molecular mechanisms of cis-9,trans-11 CLA synthesis in ruminant mammary gland are still not clearly understood. This process may be mediated, to a certain extent, by trans-11 C18:1 regulated by stearoyl-CoA desaturase-1 (SCD1) and/or its syntrophic proteins. This study aimed to investigate the effects of TVA on SCD1-mediated cis-9,trans-11 CLA synthesis in MAC-T cells and its potential molecular mechanism. Results showed that trans-11 C18:1 was continually taken up and converted into cis-9,trans-11 CLA in MAC-T cells during the 4-h incubation of 50 μM trans-11 C18:1. SCD1 protein expression increased more than twofold at 2 h (P absorption of trans-11 C18:1 in the bovine mammary gland.

  15. Purification and characterization of glucosidase I involved in N-linked glycoprotein processing in bovine mammary gland.

    Science.gov (United States)

    Shailubhai, K; Pratta, M A; Vijay, I K

    1987-11-01

    Glucosidase I, the first enzyme involved in the post-translational processing of N-linked glycoproteins, was purified to homogeneity from the lactating bovine mammary tissue. The enzyme was extracted by differential treatment of the microsomal fraction with Triton X-100 and Lubrol PX. The solubilized enzyme was subjected to affinity chromatography on Affi-Gel 102 with N-5-carboxypentyldeoxynojirimycin as ligand and DEAE-Sepharose CL-6B chromatography. Purified glucosidase I shows a molecular mass of 320-330 kDa by gel filtration on Sephacryl S-300. SDS/polyacrylamide-gel electrophoresis under reducing conditions indicates a single band of approx. 85 kDa, indicating that the native enzyme is probably a tetrameric protein. Several criteria, including pH optimum of 6.6-7.0, specific hydrolytic action towards Glc3Man9GlcNAc2, to release the terminally alpha-1,2-linked glucosyl residue, and total lack of activity towards Glc1Man9GlcNAc2 and Glc2Man9GlcNAc2 saccharides, which are the biological substrates for processing glucosidase II, and 4-methylumbelliferyl alpha-D-glucopyranoside show the non-lysosomal origin and the processing-specific role of the purified enzyme. The enzyme does not require any metal ions for its activity. Hg2+, Ag+ and Cu2+ are potent inhibitors of the enzyme; this inhibition can be reversed by adding an excess of dithiothreitol. Among the saccharides tested, kojibiose (Glc alpha 1----2Glc) was inhibitory to the enzyme. Polyclonal antibodies raised against the enzyme in rabbit were found to be specific for glucosidase I, as revealed by Western-blot analysis and by immunoadsorption with Protein A-Sepharose. Anti-(glucosidase I) antibodies were cross-reactive towards a similar antigen in solubilized microsomal preparations from liver, mammary gland and heart from the bovine, guinea pig, rat and mouse.

  16. Sunflower oil supplementation affects the expression of miR-20a-5p and miR-142-5p in the lactating bovine mammary gland.

    Directory of Open Access Journals (Sweden)

    Lenha Mobuchon

    Full Text Available Oil supplementation in dairy cattle diets is used to modulate milk fat composition, as well as the expression of mammary lipogenic genes, whose regulation remains unclear. MiRNAs are small non-coding RNA considered as crucial regulators of gene expression, offering clues to explain the mechanism underlying gene nutriregulation. The present study was designed to identify miRNAs whose expression in the cow mammary gland is modulated by sunflower oil supplementation. MiRNomes were obtained using RNAseq technology from the mammary gland of lactating cows receiving a low forage diet, supplemented or not with 4% sunflower oil. Among the 272 miRNAs characterized, eight were selected for RT-qPCR validations, showing the significant down-regulation of miR-142-5p and miR-20a-5p by sunflower supplementation. These two miRNAs are predicted to target genes whose expression was reported as differentially expressed by sunflower supplementation. Among their putative targets, ELOVL6 gene involved in lipid metabolism has been studied. However, a first analysis did not show its significant down-regulation, in response to the over-expression of miR-142-5p, of miR-20a-5p, or both, in a bovine mammary epithelial cell line. However, a clearer understanding of the miRNA expression by lipid supplementation would help to decipher the regulation of lactating cow mammary gland in response to nutrition.

  17. Differential expression and localization of lipid transporters in the bovine mammary gland during the pregnancy-lactation cycle

    DEFF Research Database (Denmark)

    Mani, O; Sørensen, M T; Sejrsen, K

    2009-01-01

    The transport of lipids across mammary gland epithelial cells (MEC) determines milk lipid content and composition. We investigated the expression of lipid transporters and their regulators in comparison to blood metabolites during lactation and dry period (DP) in dairy cows. Repeated mammary gland...... enzymatic chemistries. Elevated mRNA profiles of ABCA1 and ABCA7 were found during DP as compared with lactation and were inversely associated with blood cholesterol levels. Elevated levels of ABCG2, NPC1, SREBP1, SREBP2, LXR , and PPAR were found postpartum, whereas ABCG1 did not differ between...... the functional stages of the mammary gland. The ABCA1 protein was localized in MEC and showed differential activity between DP and lactation suggesting a role of ABCA1 in the removal of excess cellular cholesterol from MEC during the DP. The expression profiles of ABCA7 and NPC1 may reflect a role...

  18. Computational analysis of bovine milk exosomal miRNAs profiles derived from uninfected and Streptococcus uberis infected mammary gland

    Science.gov (United States)

    The dairy cattle industry in the U.S. contributes an estimated 7 billion dollars to the agribusiness economy. Bacterial infections that cause disease like mastitis, affect health of the lactating mammary gland, and negatively impacts milk production and milk quality, costing producers an estimated 2...

  19. Humanization of the mouse mammary gland.

    Science.gov (United States)

    Wronski, A; Arendt, L M; Kuperwasser, Charlotte

    2015-01-01

    Although mouse models have provided invaluable information on the mechanisms of mammary gland development, anatomical and developmental differences between human and mice limit full understanding of this fundamental process. Humanization of the mouse mammary gland by injecting immortalized human breast stromal cells into the cleared murine mammary fat pad enables the growth and development of human mammary epithelial cells or tissue. This facilitates the characterization of human mammary gland development or tumorigenesis by utilizing the mouse mammary fat pad. Here we describe the process of isolating human mammary stromal and epithelial cells as well as their introduction into the mammary fat pads of immunocompromised mice.

  20. Survey of bovine mycotic mastitis in different mammary gland statuses in two north-eastern regions of Algeria.

    Science.gov (United States)

    Ksouri, Samir; Djebir, Somia; Hadef, Youcef; Benakhla, Ahmed

    2015-04-01

    The aim of this study was to evaluate the prevalence of mycotic mastitis in different mammary gland statuses. The study was conducted on 304 dairy cows from ten farms in two north-eastern regions in Algeria; Guelma and Souk Ahras with 922 and 199 samples, respectively, forming thus a total number of 1,121 milk samples. A total of 321 milk samples were collected from clinical mastitis, 544 milk samples from subclinical mastitis and 256 milk samples from healthy mammary glands. Mycological analyses revealed that 10.17% of the treated samples were positive recording 114 species of fungi including 88 yeasts and 26 moulds. The most frequent species was Candida kefyr followed by C. albicans, C. guilliermondii, C. famata, C. tropicalis, C. colliculosa, C. krusei, C. rugosa, C. glabrata, C. parapsilosis, C. inconspicua, Trichosporon sp., Rhodotorula glutinis and Saccharomyces fragilis. Mould species have also been isolated from samples of both healthy milk and clinical mastitis milk. Aspergillus amstelodami (from glaucus group), A. fumigatus and Geotrichum candidum were identified, while the other species including Penicillium sp. and Cladosporium sp. were not identified.

  1. Perspective on calf and mammary gland development through changes in the bovine milk proteome over a complete lactation.

    Science.gov (United States)

    Zhang, Lina; Boeren, Sjef; Hageman, Jos A; van Hooijdonk, Toon; Vervoort, Jacques; Hettinga, Kasper

    2015-08-01

    Milk contains all the nutrients for the growth and development of the neonate. However, milk composition is not constant during lactation. To study the changes of the milk proteome over lactation, filter-aided sample preparation combined with dimethyl labeling followed by liquid chromatography tandem mass spectrometry was used to identify and quantify milk proteins from 4 cows. A total of 229 proteins were identified, of which 219 were quantified. An 80% overlap was found in identified and quantified proteins between the 4 individual cows during lactation. Over lactation, the number of quantified proteins changed slightly (less than 10%), whereas the concentration of proteins changed considerably. Transport proteins involved in lipid synthesis (fatty acid-binding protein, perilipin-2, butyrophilin) increased, whereas proteins related to cholesterol transport (apolipoprotein E) decreased. The changes of lipid synthesis proteins are in accordance with the increased milk fat yield over lactation, indicating the increase of de novo mammary fatty acid synthesis as lactation advances. The high abundance of immune-related proteins in early lactation indicates the important role of these proteins for immune system development of calves. The increase in immune-related proteins (immunoglobulins, osteopontin, lactoferrin) and the decrease of proteins related to milk component synthesis (α-lactalbumin, β-lactoglobulin, fatty acid-binding protein, perilipin-2, butyrophilin) in late lactation can be associated with the protection of the mammary gland. In conclusion, the changes of proteins with different biological functions reflect not only the changing needs of calves but also the development and protection of the mammary gland over lactation. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  2. Expression profiles of microRNAs from lactating and non-lactating bovine mammary glands and identification of miRNA related to lactation

    Directory of Open Access Journals (Sweden)

    Li Zhen

    2012-12-01

    Full Text Available Abstract Background MicroRNAs (miRNAs have been implicated in the regulation of milk protein synthesis and development of the mammary gland (MG. However, the specific functions of miRNAs in these regulations are not clear. Therefore, the elucidation of miRNA expression profiles in the MG is an important step towards understanding the mechanisms of lactogenesis. Results Two miRNA libraries were constructed from MG tissues taken from a lactating and a non-lactating Holstein dairy cow, respectively, and the short RNA sequences (18–30 nt in these libraries were sequenced by Solexa sequencing method. The libraries included 885 pre-miRNAs encoding for 921 miRNAs, of which 884 miRNAs were unique sequences and 544 (61.5% were expressed in both periods. A custom-designed microarray assay was then performed to compare miRNA expression patterns in the MG of lactating and non-lactating dairy cows. A total of 56 miRNAs in the lactating MG showed significant differences in expression compared to non-lactating MG (P Conclusion Our study provides a broad view of the bovine MG miRNA expression profile characteristics. Eight hundred and eighty-four miRNAs were identified in bovine MG. Differences in types and expression levels of miRNAs were observed between lactating and non-lactating bovine MG. Systematic predictions aided in the identification of lactation-related miRNAs, providing insight into the types of miRNAs and their possible mechanisms in regulating lactation.

  3. MicroRNA content in milk exosomes as a phenotypic indicator of Staphylococcus aureus infection in the bovine mammary gland

    Science.gov (United States)

    Previous gene mapping research to understand the host genetic response to mammary infection based on somatic cell score has been unsuccessful due to the poor correlation of this confounding trait with mastitis, a disease costing the dairy industry an estimated $2 billion in annual costs. Recently, ...

  4. Expression profiles of microRNAs from lactating and non-lactating bovine mammary glands and identification of miRNA related to lactation

    Science.gov (United States)

    2012-01-01

    Background MicroRNAs (miRNAs) have been implicated in the regulation of milk protein synthesis and development of the mammary gland (MG). However, the specific functions of miRNAs in these regulations are not clear. Therefore, the elucidation of miRNA expression profiles in the MG is an important step towards understanding the mechanisms of lactogenesis. Results Two miRNA libraries were constructed from MG tissues taken from a lactating and a non-lactating Holstein dairy cow, respectively, and the short RNA sequences (18–30 nt) in these libraries were sequenced by Solexa sequencing method. The libraries included 885 pre-miRNAs encoding for 921 miRNAs, of which 884 miRNAs were unique sequences and 544 (61.5%) were expressed in both periods. A custom-designed microarray assay was then performed to compare miRNA expression patterns in the MG of lactating and non-lactating dairy cows. A total of 56 miRNAs in the lactating MG showed significant differences in expression compared to non-lactating MG (P<0.05). Integrative miRNA target prediction and network analysis approaches were employed to construct an interaction network of lactation-related miRNAs and their putative targets. Using a cell-based model, six miRNAs (miR-125b, miR-141, miR-181a, miR-199b, miR-484 and miR-500) were studied to reveal their possible biological significance. Conclusion Our study provides a broad view of the bovine MG miRNA expression profile characteristics. Eight hundred and eighty-four miRNAs were identified in bovine MG. Differences in types and expression levels of miRNAs were observed between lactating and non-lactating bovine MG. Systematic predictions aided in the identification of lactation-related miRNAs, providing insight into the types of miRNAs and their possible mechanisms in regulating lactation. PMID:23270386

  5. Effects of bovine mammary gland biopsy and increased milking frequency on post-procedure udder health, histology, and milk yield.

    Science.gov (United States)

    Lima, J A M; Ruas, J R M; Vasconcelos, A C; Silper, B F; Lana, A M Q; Gheller, V A; Saturnino, H M; Reis, R B; Coelho, S G

    2016-05-01

    Sixteen cows in early lactation were randomly distributed into two groups in order to evaluate the effects of mammary biopsies and increased milking frequency on tissue characteristics, post-biopsy udder health and histology. One group was milked twice a day (2×) starting on the 2nd day after calving, until 28 days in milk (DIM). The other group was milked four times a day (4×) from two to 21 DIM, and twice a day (2×) from 22 to 28 DIM. On days 2, 7, 14, 21, and 28 postpartum, one fragment of secretory tissue was collected from one mammary quarter at a time. Collections were alternated between the four mammary quarters per collection day. A total of 80 mammary tissue samples were collected. Qualitative and quantitative analyses of the tissues were conducted by histologic examination. Animal health was assessed by observation of feed intake behavior immediately after biopsy, and weight and body condition score before and one week after biopsy. Udder health was assessed daily from calving to 60 DIM with California Mastitis Test (CMT) and by noting alterations in the milk such as blood, milk clots, blood clots, clinical signs of mastitis. Milk composition and somatic cell count (SCC) were analyzed before and after the biopsies. Milk production was evaluated before biopsy, on the day of biopsy, and after the biopsy. An average of 10 fields at 40× magnification was obtained from each sample. There were no evident changes in mammary morphology as a result of milking two or four times/day at any of the evaluated time points. Biopsy wounds healed rapidly without infection. Intramammary bleeding and CMT alterations were observed in 96% and 75% of the biopsied mammary quarters, respectively. Clinical mastitis was diagnosed in 12% of the biopsied quarters. Different milking frequencies had no effect on the frequency and duration of post-biopsy alterations. Milk production decreased after biopsies done on days 2 for 2× and 4× groups, but it returned to pre-biopsy values

  6. Effects of Chain Length and Saturability of Fatty Acids on Phospholipids and Proteins in Plasma Membranes of Bovine Mammary Gland.

    Science.gov (United States)

    Yan, Qiongxian; Tang, Shaoxun; Han, Xuefeng; Bamikole, Musibau Adungbe; Zhou, Chuanshe; Kang, Jinhe; Wang, Min; Tan, Zhiliang

    2016-12-01

    Free fatty acids (FFAs) in plasma are essential substrates for de novo synthesis of milk fat, or directly import into mammary cells. The physico-chemical properties of mammary cells membrane composition affected by FFAs with different chain lengths and saturability are unclear yet. Employing GC, FTIR and fluorescence spectroscopy, the adsorption capacity, phospholipids content, membrane proteins conformation, lipid peroxidation product, and free sulfhydryl of plasma membranes (PMs) interacted with different FFAs were determined. The mammary cells PMs at 38 and 39.5 °C showed different adsorption capacities: acetic acid (Ac) > stearic acid (SA) > β-hydroxybutyric acid (BHBA) > trans10, cis12 CLA. In the FTIR spectrum, the major adsorption peaks appeared at 2920 and 2850 cm -1 for phospholipids, and at 1628 and 1560 cm -1 for membrane proteins. The intensities of PMs-FFAs complexes were varied with the FFAs species and their initial concentrations. The β-sheet and turn structures of membrane proteins were transferred into random coil and α-helix after BHBA, SA and trans10, cis12 CLA treatments compared with Ac treatment. The quenching effects on the fluorescence of endogenous membrane protein, 1, 8-ANS, NBD-PE, and DHPE entrapped in PMs by LCFA were different from those of short chain FFAs. These results indicate that the adsorption of FFAs could change membrane protein conformation and polarity of head group in phospholipids. This variation of the mammary cells PMs was regulated by carbon chain length and saturability of FFAs.

  7. Evaluation of the Rapid Mastitis Test for identification of Staphylococcus aureus and Streptococcus agalactiae isolated from bovine mammary glands.

    OpenAIRE

    Watts, J L; Owens, W E

    1988-01-01

    A latex agglutination test system (Rapid Mastitis Test [RMT]; Immucell, Portland, Maine) containing reagents for the identification of Staphylococcus aureus and Streptococcus agalactiae from bovine intramammary infections was evaluated with 527 staphylococcal and 267 streptococcal isolates. The RMT Staphylococcus aureus reagent detected 94.2% of 242 Staphylococcus aureus isolates, 80% of 25 Staphylococcus intermedius isolates, and 42.8% of 21 tube coagulase-positive Staphylococcus hyicus isol...

  8. Mammary gland stem cells: More puzzles than explanations

    Indian Academy of Sciences (India)

    Mammary gland stem cells (MaSC) have not been identified in spite of extensive research spanning over several decades. This has been primarily due to the complexity of mammary gland structure and its development, cell heterogeneity in the mammary gland and the insufficient knowledge about MaSC markers.

  9. Human milk protein production in xenografts of genetically engineered bovine mammary epithelial stem cells.

    Science.gov (United States)

    Martignani, Eugenio; Eirew, Peter; Accornero, Paolo; Eaves, Connie J; Baratta, Mario

    2010-10-19

    In the bovine species milk production is well known to correlate with mammary tissue mass. However, most advances in optimizing milk production relied on improvements of breeding and husbandry practices. A better understanding of the cells that generate bovine mammary tissue could facilitate important advances in milk production and have global economic impact. With this possibility in mind, we show that a mammary stem cell population can be functionally identified and isolated from the bovine mammary gland. We also demonstrate that this stem cell population may be a promising target for manipulating the composition of cow's milk using gene transfer. We show that the in vitro colony-forming cell assay for detecting normal primitive bipotent and lineage-restricted human mammary clonogenic progenitors are applicable to bovine mammary cells. Similarly, the ability of normal human mammary stem cells to regenerate functional bilayered structures in collagen gels placed under the kidney capsule of immunodeficient mice is shared by a subset of bovine mammary cells that lack aldehyde dehydrogenase activity. We also find that this activity is a distinguishing feature of luminal-restricted bovine progenitors. The regenerated structures recapitulate the organization of bovine mammary tissue, and milk could be readily detected in these structures when they were assessed by immunohistochemical analysis. Transplantation of the bovine cells transduced with a lentivirus encoding human β-CASEIN led to expression of the transgene and secretion of the product by their progeny regenerated in vivo. These findings point to a common developmental hierarchy shared by human and bovine mammary glands, providing strong evidence of common mechanisms regulating the maintenance and differentiation of mammary stem cells from both species. These results highlight the potential of novel engineering and transplant strategies for a variety of commercial applications including the production of

  10. Technical note: Mammary gland ultrasonography to evaluate mammary parenchymal composition in prepubertal heifers.

    Science.gov (United States)

    Albino, R L; Guimarães, S E F; Daniels, K M; Fontes, M M S; Machado, A F; Dos Santos, G B; Marcondes, M I

    2017-02-01

    Bovine mammary gland development studies are often terminal or involve invasive biopsy procedures. Therefore, noninvasive means of assessing mammary development should be considered as alternative methods in live animals. The objective was to test if mammary ultrasonography can be used as a noninvasive way to estimate mammary parenchyma (PAR) composition in prepubertal dairy heifers with different average daily body weight gains. In the 84 d preceding, the ultrasound exam heifers were maintained in 1 of 3 treatment groups. Individual heifers were fed a high gain (1 kg/d; n = 6), low gain (0.5 kg/d, n = 6), or maintenance (n = 6) treatment diet. To achieve desired body weight gains, heifers were fed differing amounts of the same silage-based diet. Mammary glands of 18 crossbred heifers Holstein:Gyr underwent a single mammary ultrasound exam immediately before heifer slaughter, which took place when heifers weighed 142.0 ± 8.0 kg and were 200 d old. The 4 mammary glands of each heifer were evaluated using a real-time B-mode ultrasound machine equipped with a 6.5-MHz micro-convex transducer. Digital images (8-bit) of glands were obtained and PAR was identified within gland. Average pixel values per unit of PAR area were determined for each gland and analyzed at the level of heifer. Pixel results were interpreted on the basis that lower average pixel values reflect PAR with relatively high amounts of protein as opposed to fat. To help validate that the pixel value within PAR is associated with composition of PAR, pixel findings were compared with histological [number of adipocytes in PAR (Nad) and epithelial area in PAR (Ep)] and biochemical [percent crude protein in PAR (%CP), percent ether extract in PAR (%EE), PAR weight (WPAR), and mammary fat pad weight (WFAT)] composition of PAR in these same heifers. Within PAR, %EE and WFAT were positively correlated with pixel values, whereas %CP, Ep, and Nad were negatively correlated. Parenchyma weight did not correlate

  11. FRACTAL DIMENSIONALITY ANALYSIS OF MAMMARY GLAND THERMOGRAMS

    OpenAIRE

    Yu. E. Lyah; V. G. Guryanov; E. A. Yakobson

    2016-01-01

    Thermography may enable early detection of a cancer tumour within a mammary gland at an early, treatable stage of the illness, but thermogram analysis methods must be developed to achieve this goal. This study analyses the feasibility of applying the Hurst exponent readings algorithm for evaluation of the high dimensionality fractals to reveal any possible difference between normal thermograms (NT) and malignant thermograms (MT).

  12. Gynecomastia and mammary gland adenocarcinoma in a Nubian buck.

    Science.gov (United States)

    Wooldridge, A A; Gill, M S; Lemarchand, T; Eilts, B; Taylor, H W; Otterson, T

    1999-09-01

    A 6-year-old Nubian buck was presented for bilateral mammary gland enlargement. Gynecomastia and mastitis were diagnosed, and bilateral mastectomy was performed. Histological examination showed mammary adenocarcinoma, active lactation, hyperplasia, and abscessation. Karyotyping showed a normal male. Clinical, therapeutic, etiologic, and epidemiologic aspects of gynecomastia and mammary gland adenocarcinoma are discussed.

  13. Gynecomastia and mammary gland adenocarcinoma in a Nubian buck.

    OpenAIRE

    Wooldridge, A A; Gill, M S; Lemarchand, T; Eilts, B; Taylor, H. W.; Otterson, T

    1999-01-01

    A 6-year-old Nubian buck was presented for bilateral mammary gland enlargement. Gynecomastia and mastitis were diagnosed, and bilateral mastectomy was performed. Histological examination showed mammary adenocarcinoma, active lactation, hyperplasia, and abscessation. Karyotyping showed a normal male. Clinical, therapeutic, etiologic, and epidemiologic aspects of gynecomastia and mammary gland adenocarcinoma are discussed.

  14. In depth analysis of genes and pathways of the mammary gland involved in the pathogenesis of bovine Escherichia coli-mastitis

    DEFF Research Database (Denmark)

    Buitenhuis, Albert Johannes; Rontved, Christine M.; Edwards, Stefan McKinnon

    2011-01-01

    infection is necessary. To this end, we performed a global gene-expression analysis of mammary gland tissue collected from dairy cows that had been exposed to a controlled E. coli infection. Biopsy samples of healthy and infected utter tissue were collected at T=24h post-infection (p.i.) and at T=192h p.......i. to represent the acute phase response (APR) and chronic stage, respectively. Differentially expressed (DE) genes for each stage were analyzed and the DE genes detected at T=24h were also compared to data collected from two previous E. coli mastitis studies that were carried out on post mortem tissue. Results...... Nine-hundred-eighty-two transcripts were found to be differentially expressed in infected tissue at T=24 (P

  15. FRACTAL DIMENSIONALITY ANALYSIS OF MAMMARY GLAND THERMOGRAMS

    Directory of Open Access Journals (Sweden)

    Yu. E. Lyah

    2016-06-01

    Full Text Available Thermography may enable early detection of a cancer tumour within a mammary gland at an early, treatable stage of the illness, but thermogram analysis methods must be developed to achieve this goal. This study analyses the feasibility of applying the Hurst exponent readings algorithm for evaluation of the high dimensionality fractals to reveal any possible difference between normal thermograms (NT and malignant thermograms (MT.

  16. Positional Variations in Mammary Gland Development and Cancer

    OpenAIRE

    Veltmaat, Jacqueline M.; Ramsdell, Ann F.; Sterneck, Esta

    2013-01-01

    Most mammals develop their mammary glands in pairs of which the two counterparts are symmetrically displaced away from the ventral midline. Based on this symmetry and the same functional outcome as a milk-producing organ, the mammary glands are easily presumed to be mere copies of one another. Based on our analysis of published data with inclusion of new results related to mammary development and pathology in mice, we argue that this presumption is incorrect: Between and within pairs, mammary...

  17. Targeting the Prometastatic Microenvironment of the Involuting mammary gland

    Science.gov (United States)

    2016-09-01

    AWARD NUMBER: W81XWH-13-1-0290 TITLE: Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland PRINCIPAL INVESTIGATOR...2016 4. TITLE AND SUBTITLE Targeting the Prometastatic Microenvironment of the Involuting mammary gland 5a. CONTRACT NUMBER Mammary Gland 5b. GRANT...complete) Task 3) Determine the pathological significance of gain and loss of LTBP1 in genetically engineered mouse models. (75% complete) Ø

  18. Mammary gland pathologies in the parturient buffalo

    Directory of Open Access Journals (Sweden)

    G N Purohit

    2014-12-01

    Full Text Available Parturition related mammary gland pathologies in the buffalo appear to be low on accord of anatomic (longer teat length, thicker streak canal and physiologic (lower cisternal storage of secreted milk, lower milk production differences with cattle. Hemolactia, udder edema and hypogalactia usually occur in the buffalo due to physiologic changes around parturition however mastitis involves pathologic changes in the udder and teats; the incidence of mastitis is however lower compared to cattle. The incidence and therapy of hemolactia, udder edema and hypogalactia are mentioned and the risk factors, incidence, diagnosis, therapy and prevention for mastitis in buffalo are also described.

  19. Bovine mammary stem cells: cell biology meets production agriculture.

    Science.gov (United States)

    Capuco, A V; Choudhary, R K; Daniels, K M; Li, R W; Evock-Clover, C M

    2012-03-01

    Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue repair. Accordingly, we and others have attempted to characterize and alter the function of bovine MaSC. In this review, we provide an overview of current knowledge of MaSC gained from studies using mouse and human model systems and present research on bovine MaSC within that context. Recent data indicate that MaSC retain labeled DNA for extended periods because of their selective segregation of template DNA strands during mitosis. Relying on this long-term retention of bromodeoxyuridine-labeled DNA, we identified putative bovine MaSC. These label-retaining epithelial cells (LREC) are in low abundance within mammary epithelium (laser microdissection and subsequent microarray analysis will hopefully provide markers for MaSC and insights into their regulation. Preliminary analyses of gene expression in laser-microdissected LREC and non-LREC are consistent with the concept that LREC represent populations of stem cells and progenitor cells that differ with regard to their properties and location within the epithelial layer. We have attempted to modulate the MaSC number by infusing a solution of xanthosine through the teat canal and into the ductal network of the mammary glands of prepubertal heifers. This treatment increased the number of putative stem cells, as evidenced by an increase in the percentage of LREC and increased telomerase activity within the tissue. The exciting possibility that stem cell expansion can influence milk production is currently under investigation.

  20. Oxytocin binding sites in bovine mammary tissue

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Xin.

    1989-01-01

    Oxytocin binding sites were identified and characterized in bovine mammary tissue. ({sup 3}H)-oxytocin binding reached equilibrium by 50 min at 20{degree}C and by 8 hr at 4{degree}C. The half-time of displacement at 20{degree}C was approximately 1 hr. Thyrotropin releasing hormone, adrenocorticotropin, angiotensin I, angiotensin II, pentagastrin, bradykinin, xenopsin and L-valyl-histidyl-L-leucyl-L-threonyl-L-prolyl-L-valyl-L-glutamyl-L-lysine were not competitive. In the presence of 10 nM LiCl, addition of oxytocin to dispersed bovine mammary cells, in which phosphatidylinositol was pre-labelled, caused a time and dose-dependent increase in radioactive inositiol monophosphate incorporation. The possibility that there are distinct vasopressin receptors in bovine mammary tissue was investigated. ({sup 3}H)-vasopressin binding reached equilibrium by 40 min at 20{degree}. The half-time of displacement at 20{degree}C was approximately 1 hr. The ability of the peptides to inhibit ({sup 3}H)-vasopressin binding was: (Thr{sup 4},Gly{sup 7})-oxytocin > Arg{sup 8}-vasopressin > (lys{sup 8})-vasopressin > (Deamino{sup 1},D-arg{sup 8})-vasopressin > oxytocin > d (CH{sub 2}){sub 5}Tyr(Me)AVP.

  1. Effects of N-acetylimidazole on oxytocin binding in bovine mammary tissue

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, X.; Gorewit, R.C.; Currie, W.B. (Cornell Univ., Ithaca NY (USA))

    1990-01-01

    The effects of N-acetylimidazole on specific binding of oxytocin to microsomal fractions of bovine mammary gland were studied. N-acetylimidazole suppressed oxytocin binding, with time and concentration dependence. Decreased oxytocin binding activity appeared to be due to decreased affinity of the hormone for its receptor. Acetylation of oxytocin, rather than of oxytocin receptors, seemed to be responsible for the decreased binding.

  2. Development of mammary glands of fat sheep submitted to restricted feeding during late pregnancy

    DEFF Research Database (Denmark)

    Nørgaard, J V; Nielsen, M O; Theil, P K

    2008-01-01

    Mammary gland development in sheep occurs mainly during puberty and pregnancy. We have investigated the effects of a late gestation feed restriction on mammary gland development in sheep.......Mammary gland development in sheep occurs mainly during puberty and pregnancy. We have investigated the effects of a late gestation feed restriction on mammary gland development in sheep....

  3. ABC- and SLC-Transporters in Murine and Bovine Mammary Epithelium

    DEFF Research Database (Denmark)

    Yagdiran, Yagmur; Oskarsson, Agneta; Knight, Christopher H.

    2016-01-01

    , previously reported toinfluence BCRP in mammary cells, was investigated on transporter expression and functionin the two cell lines. Transporters studied were BCRP, MDR1, MRP1, OATP1A5/OATP1A2,OCTN1 and OCT1. Gene expressions of BCRP and OCT1 in murine mammary glandswere increased during gestation...... and lactation, whereas MDR1, MRP1, OATP1A5 and OCTN1 were decreased, compared to expressions in virgins. All transporters measured inmammary glands of mice were detected in bovine mammary tissue and in HC11 cells, while only MDR1 and MRP1 were detected in BME-UV cells. Prochloraz treatment induced MDR1 gene...

  4. Mammary gland tumors in a male Cocker Spaniel.

    Science.gov (United States)

    Kwon, Soon-Chan; Yoo, Dae-Young; Ko, Minho; Lee, Kwon-Young; Kwak, Ho-Hyun; Park, In-Chul; Hwang, In-Koo; Choi, Jung-Hoon; Chung, Jin-Young

    2017-04-11

    Mammary gland tumors are the most common tumors in sexually intact female dogs; however, they are rare in male dogs. This study was conducted to investigate the relationship between sexual hormones and mammary gland tumors in a male dog. A 13-year-old, intact male Cocker Spaniel presented to the Veterinary Teaching Hospital of Kangwon National University, Republic of Korea, with an acute right ruptured caudal abdominal mass. Physical examination revealed a 14 × 14 cm ruptured mass in the right caudal abdomen, as well as a 1.5 × 1.5 cm mass in the first right mammary gland. The estrogen and progesterone concentrations in serum were within normal levels. Total mastectomy was done on the right side mammary glands. Following surgery, the site was fully recovered; however, a mass that had grown to 2 × 2 cm was found in the left fifth mammary gland and a testis tumor was also found over the period of 4 months. Mastectomy was performed on the left caudal mammary gland and castration was also performed. After the final surgery, the dog fully recovered. Histopathological examination of all three masses revealed high grade mammary adenocarcinoma in the mammary gland and the testis was diagnosed as Leydig cell adenoma. Immunohistochemical analysis revealed that the estrogen and progesterone receptors were expressed on limited cells in mammary and testis tumors. The results of this study suggest that mammary tumors and testes tumors can occur in male dogs without relationship to female sexual hormone.

  5. Stromal Effects on Mammary Gland Development and Breast Cancer

    Science.gov (United States)

    Wiseman, Bryony S.; Werb, Zena

    2002-05-01

    Breast cancer manifests itself in the mammary epithelium, yet there is a growing recognition that mammary stromal cells also play an important role in tumorigenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer, and many of the stromal factors necessary for mammary development also promote or protect against breast cancer. Here we review our present knowledge of the specific factors and cell types that contribute to epithelial-stromal crosstalk during mammary development. To find cures for diseases like breast cancer that rely on epithelial-stromal crosstalk, we must understand how these different cell types communicate with each other.

  6. Mammary blood flow and cardiac output during initiated involution of the mammary gland in the rabbit.

    Science.gov (United States)

    Jones, C S; Parker, D S

    1988-01-01

    1. Cardiac output and its distribution to the mammary gland, kidneys, heart, liver and gastrointestinal tract were measured in conscious rabbits at day 1, day 3 and day 6 after removal of the young at day 0. 2. There was no change in cardiac output, proportion of cardiac output delivered to the mammary gland or mammary blood flow 24 hr after the last suckling period. After a further 48 hr there was a significant reduction in the cardiac output, proportion of the cardiac output and blood flow to the mammary gland compared to the values measured in lactating animals. 3. There was no significant difference in blood flow to the other organs although there were changes in the proportion of the cardiac output delivered to the heart, kidney and liver during this period. 4. The change in uptake of glucose, acetate, non-esterified fatty acids and triacylglycerols by the mammary gland are discussed in relation to the reabsorption of milk components.

  7. Squamous Cell Carcinoma of Mammary Gland in Domestic Cat

    OpenAIRE

    Filgueira,Kilder Dantas; Reche Junior,Archivaldo

    2012-01-01

    Background: In the feline species, 80% to 93% of neoplasias in the mammary gland are malignant, being the majority carcinomas. Among them, there is the mammary squamous cell carcinoma, which amounts to a very rare neoplasm in the domestic cat, with considerable potential for malignancy. This study aimed to report a case of squamous cell mammary carcinoma in the feline species. Case: A female cat, mixed breed, ten years old, presented history of skin lesion. The cat had been spayed two years b...

  8. Induction of mammary gland tumor in female Sprague- Dawley rats ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-07-12

    Jul 12, 2010 ... hormone sensitivity and histology. There is no other animal tumor comparable to these models because of the similarity in the function and structure of certain rat mammary tumors to hormone-sensitive human breast cancer (Young and Hallowers, 1973). Mammary gland LA7 cells were isolated in 1979 ...

  9. Resident macrophages influence stem cell activity in the mammary gland

    NARCIS (Netherlands)

    Gyorki, D.E.; Asselin-Labat, M.L.; Rooijen, van N.; Lindeman, G.J.; Visvader, J.E.

    2009-01-01

    Introduction Macrophages in the mammary gland are essential for morphogenesis of the ductal epithelial tree and have been implicated in promoting breast tumor metastasis. Although it is well established that macrophages influence normal mammopoiesis, the mammary cell types that these accessory cells

  10. Imunidade inata da glândula mamária bovina: resposta à infecção Innate immunity of the bovine mammary gland: response to infection

    Directory of Open Access Journals (Sweden)

    Deolinda Maria Vieira Filha Carneiro

    2009-09-01

    infection's site by numerous stimulations, and these answers are not enhanced by repeated exposure to the same agent. The first obstacle to be faced by the agent is the barrier represented by the teat sphincter and the keratin plug. When the pathogenic agent crosses the teat canal and reaches the teat cistern, starts to act the humoral factors and the phagocytic cells starts do act. Among the humoral mediators there are the lactoperoxidase, complement, cytokines, lactoferrin, lysozyme and NAGase. The non-specific cellular defenses are represented by neutrophils, macrophages and natural killer cells. If these mechanisms have been functioning adequately, the majority of pathogens will be eliminated in a short time, before the specific immune system be activated. The fast elimination of the microorganisms will not allow these alterations in the amount or quality of produced milk. The best understanding of the defense mechanisms of the mammary gland and its alterations during the critical periods of infection, is an useful tool in devising and developing methods to control the mastitis, the major illness of dairy ruminants. This paper overviewed the most important aspects of the innate immunity of bovine mammary gland.

  11. Xanthosine administration does not affect the proportion of epithelial stem cells in bovine mammary tissue, but has a latent negative effect on cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Rauner, Gat, E-mail: gat.rauner@mail.huji.ac.il [Institute of Animal Science, ARO, The Volcani Center, P.O. Box 6, Bet-Dagan, 50250 (Israel); The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem (Israel); Barash, Itamar, E-mail: itamar.barash@mail.huji.ac.il [Institute of Animal Science, ARO, The Volcani Center, P.O. Box 6, Bet-Dagan, 50250 (Israel)

    2014-10-15

    The challenge in manipulating the proportion of somatic stem cells lies in having to override tissue homeostasis. Xanthosine infusion via the teat canal has been reported to augment the number of label-retaining cells in the mammary gland of 3-month-old bovine calves. To further delineate xanthosine's effect on defined stem cells in the mammary gland of heifers—which are candidates for increased prospective milk production following such manipulation—bovine mammary parenchymal tissue was transplanted and integrated into the cleared mammary fat pad of immunodeficient mice. Xanthosine administration for 14 days did not affect the number of label-retaining cells after 10- and 11-week chases. No change in stem cell proportion, analyzed according to CD49f and CD24 expression, was noted. Clone formation and propagation rate of cultured cells, as well as expression of stem cell markers, were also unaffected. In contrast, a latent 50% decrease in bovine mammary cell proliferation rate was observed 11 weeks after xanthosine administration. Tumor development in mice was also limited by xanthosine administration. These effects may have resulted from an initial decrease in expression of the rate-limiting enzyme in guanine synthesis, IMPDH. The data indicate that caution should be exerted when considering xanthosine for stem cell manipulation. - Highlights: • Novel “bovinized“ mouse model for exogenous effects on bovine mammary gland. • Xanthosine did not affect stem cell number/function in bovine mammary gland. • Xanthosine caused an immediate decrease in IMPDH expression in bovine mammary gland. • Xanthosine had latent negative effect on cell proliferation in bovine mammary gland. • Xanthosine administration limited mammary tumor growth.

  12. Luminal progenitors restrict their lineage potential during mammary gland development.

    Science.gov (United States)

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-02-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.

  13. Mammary analogue secretory carcinoma: A rare salivary gland tumour

    African Journals Online (AJOL)

    Salivary gland malignancy is rare, with a global annual incidence of. 3 per 100 000 people.[1,2] A rare salivary gland tumour, mammary analogue secretory carcinoma (MASC), has only recently been described.[3] The few reports and studies concerning MASC have been published in several pathology journals. We report ...

  14. Functional adaptations of the transcriptome to mastitis-causing pathogens: the mammary gland and beyond.

    Science.gov (United States)

    Loor, Juan J; Moyes, Kasey M; Bionaz, Massimo

    2011-12-01

    Application of microarrays to the study of intramammary infections in recent years has provided a wealth of fundamental information on the transcriptomics adaptation of tissue/cells to the disease. Due to its heavy toll on productivity and health of the animal, in vivo and in vitro transcriptomics works involving different mastitis-causing pathogens have been conducted on the mammary gland, primarily on livestock species such as cow and sheep, with few studies in non-ruminants. However, the response to an infectious challenge originating in the mammary gland elicits systemic responses in the animal and encompasses tissues such as liver and immune cells in the circulation, with also potential effects on other tissues such as adipose. The susceptibility of the animal to develop mastitis likely is affected by factors beyond the mammary gland, e.g. negative energy balance as it occurs around parturition. Objectives of this review are to discuss the use of systems biology concepts for the holistic study of animal responses to intramammary infection; providing an update of recent work using transcriptomics to study mammary and peripheral tissue (i.e. liver) as well as neutrophils and macrophage responses to mastitis-causing pathogens; discuss the effect of negative energy balance on mastitis predisposition; and analyze the bovine and murine mammary innate-immune responses during lactation and involution using a novel functional analysis approach to uncover potential predisposing factors to mastitis throughout an animal's productive life.

  15. Mammary analogue secretory carcinoma: A rare salivary gland tumour

    Directory of Open Access Journals (Sweden)

    B S Jackson

    2017-04-01

    Full Text Available Mammary analogue secretory carcinoma (MASC is a rare and recently described tumour of the salivary glands. MASC has similar histomorphological and immunohistochemical features of secretory carcinoma of the breast. MASC can be mistaken for other salivary gland tumours, especially acinic cell carcinoma. A 28-year-old man was diagnosed with a rare salivary gland tumour in Pretoria, South Africa (SA. To our knowledge, a report of MASC in SA has not previously been published. The surgeons dealing with salivary gland tumours should be aware of the clinical presentation. Current treatment is similar to that of other salivary gland malignancies.

  16. Mammary analogue secretory carcinoma: A rare salivary gland tumour.

    Science.gov (United States)

    Jackson, B S; Pratt, T L; Van Rooyen, A

    2017-03-29

    Mammary analogue secretory carcinoma (MASC) is a rare and recently described tumour of the salivary glands. MASC has similar histomorphological and immunohistochemical features of secretory carcinoma of the breast. MASC can be mistaken for other salivary gland tumours, especially acinic cell carcinoma. A 28-year-old man was diagnosed with a rare salivary gland tumour in Pretoria, South Africa (SA). To our knowledge, a report of MASC in SA has not previously been published. The surgeons dealing with salivary gland tumours should be aware of the clinical presentation. Current treatment is similar to that of other salivary gland malignancies.

  17. Disruption of reelin signaling alters mammary gland morphogenesis

    Science.gov (United States)

    Khialeeva, Elvira; Lane, Timothy F.; Carpenter, Ellen M.

    2011-01-01

    Reelin signaling is required for appropriate cell migration and ductal patterning during mammary gland morphogenesis. Dab1, an intracellular adaptor protein activated in response to reelin signaling, is expressed in the developing mammary bud and in luminal epithelial cells in the adult gland. Reelin protein is expressed in a complementary pattern, first in the epithelium overlying the mammary bud during embryogenesis and then in the myoepithelium and periductal stroma in the adult. Deletion in mouse of either reelin or Dab1 induced alterations in the development of the ductal network, including significant retardation in ductal elongation, decreased terminal branching, and thickening and disorganization of the luminal wall. At later stages, some mutant glands overcame these early delays, but went on to exhibit enlarged and chaotic ductal morphologies and decreased terminal branching: these phenotypes are suggestive of a role for reelin in spatial patterning or structural organization of the mammary epithelium. Isolated mammary epithelial cells exhibited decreased migration in response to exogenous reelin in vitro, a response that required Dab1. These observations highlight a role for reelin signaling in the directed migration of mammary epithelial cells driving ductal elongation into the mammary fat pad and provide the first evidence that reelin signaling may be crucial for regulating the migration and organization of non-neural tissues. PMID:21266412

  18. Mechanisms Underlying the Very High Susceptibility of the Immature Mammary Gland to Carcinogenic Initiation

    National Research Council Canada - National Science Library

    Gould, Michael

    2000-01-01

    The overall goal of this project was to explore the toxic effects of physical and chemical carcinogens on the immature mammary gland as compared to the effects on the young adult mammary gland using a rat model. We have: I...

  19. Effects of short- and long-chain fatty acids on the expression of stearoyl-CoA desaturase and other lipogenic genes in bovine mammary epithelial cells

    NARCIS (Netherlands)

    Jacobs, A.A.A.; Dijkstra, J.; Liesman, J.S.; VandeHaar, M.J.; Lock, A.L.; Vuuren, van A.M.; Hendriks, W.H.; Baal, van J.

    2013-01-01

    Stearoyl-CoA desaturase (SCD) in the bovine mammary gland introduces a cis-double bond at the ¿9 position in a wide range of fatty acids (FA). Several long-chain polyunsaturated fatty acids (PUFA) inhibit expression of SCD, but information on the effect of short-chain fatty acids on mammary SCD

  20. File list: Unc.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Brs.05.AllAg.Mammary_glands mm9 Unclassified Breast Mammary glands SRX216177 ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.05.AllAg.Mammary_glands.bed ...

  1. File list: Oth.Brs.50.AllAg.Mammary_glands [Chip-atlas[Archive

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  15. File list: Pol.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: His.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. MiR-15a Decreases Bovine Mammary Epithelial Cell Viability and Lactation and Regulates Growth Hormone Receptor Expression

    Directory of Open Access Journals (Sweden)

    Xue-Jun Gao

    2012-10-01

    Full Text Available MicroRNAs (miRNAs are a class of small non-coding RNAs that regulate the expression of target genes at the post-transcriptional level by transcript degradation or translational inhibition. The role of bta-miR-15a in bovine mammary gland hasn’t been reported. Using miRNAs prediction software, GHR gene was predicted to be a potential target of bta-miR-15a. In this study, bovine mammary epithelial cell line was used as an in vitro cell model to address the function of bta-miR-15a on bovine mammary epithelial cells. The expression changes of bta-miR-15a and Ghr after bta-miR-15a transfection were detected by qRT-PCR; the expression of GHR protein and casein was detected by western blotting. To determine whether bta-miR-15a can affect cell viability, cells were examined using an electronic Coulter counter (CASY-TT. In conclusion, bta-miR-15a inhibited the expression of casein of bovine mammary epithelial cells, and cell number and viability were reduced by bta-miR-15a expression. Bta-miR-15a inhibited the viability of mammary epithelial cells as well as the expression of GHR mRNA and protein level, therefore suggesting that bta-miR-15a may play an important role in mammary gland physiology.

  3. Farrerol regulates antimicrobial peptide expression and reduces Staphylococcus aureus internalization into bovine mammary epithelial cells.

    Science.gov (United States)

    Yang, Zhengtao; Fu, Yunhe; Liu, Bo; Zhou, Ershun; Liu, Zhicheng; Song, Xiaojing; Li, Depeng; Zhang, Naisheng

    2013-12-01

    Mastitis, defined as inflammation of the mammary gland, is an infectious disease with a major economic influence on dairy industry. Staphylococcus aureus is a common gram-positive pathogen that frequently causes subclinical, chronic infection of the mammary gland in dairy cows. Farrerol, a traditional Chinese medicine isolated from rhododendron, has been shown to have anti-bacterial activity. However, the effect of farrerol on S. aureus infection in mammary epithelium has not been studied in detail. The aim of this study was to investigate the effect of farrerol on the invasion of bovine mammary epithelial cells (bMEC) by S. aureus. The expression of antimicrobial peptide genes by bMEC were assessed in the presence or absence of S. aureus infection. Our results demonstrated that farrerol (4-16 μg/ml) reduced > 55% the internalization of S. aureus into bMEC. We also found that farrerol was able to down-regulate the mRNA expression of tracheal antimicrobial peptide (TAP) and bovine neutrophil β-defensin 5 (BNBD5) in bMEC infected with S. aureus. The Nitric oxide (NO) production of bMEC after S. aureus stimulation was decreased by farrerol treatment. Furthermore, farrerol treatment suppressed S. aureus-induced NF-κB activation in bMEC. These results demonstrated that farrerol modulated TAP and BNBD5 gene expression in mammary gland, enhances bMEC defense against S. aureus infection and could be useful in protection against bovine mastitis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. The mammary gland in domestic ruminants: a systems biology perspective.

    Science.gov (United States)

    Ferreira, Ana M; Bislev, Stine L; Bendixen, Emøke; Almeida, André M

    2013-12-06

    Milk and dairy products are central elements in the human diet. It is estimated that 108kg of milk per year are consumed per person worldwide. Therefore, dairy production represents a relevant fraction of the economies of many countries, being cattle, sheep, goat, water buffalo, and other ruminants the main species used worldwide. An adequate management of dairy farming cannot be achieved without the knowledge on the biological mechanisms behind lactation in ruminants. Thus, understanding the morphology, development and regulation of the mammary gland in health, disease and production is crucial. Presently, innovative and high-throughput technologies such as genomics, transcriptomics, proteomics and metabolomics allow a much broader and detailed knowledge on such issues. Additionally, the application of a systems biology approach to animal science is vastly growing, as new advances in one field of specialization or animal species lead to new lines of research in other areas or/and are expanded to other species. This article addresses how modern research approaches may help us understand long-known issues in mammary development, lactation biology and dairy production. Dairy production depends upon the knowledge of the morphology and regulation of the mammary gland and lactation. High-throughput technologies allow a much broader and detailed knowledge on the biology of the mammary gland. This paper reviews the major contributions that genomics, transcriptomics, metabolomics and proteomics approaches have provided to understand the regulation of the mammary gland in health, disease and production. In the context of mammary gland "omics"-based research, the integration of results using a Systems Biology Approach is of key importance. © 2013.

  5. Comparative characteristics of mammary glands cancer in humans and animals

    Directory of Open Access Journals (Sweden)

    Vorobyova О.V.

    2012-09-01

    Full Text Available

     

    This review is devoted to a comparative analysis of receptor status, immunity, angiogenesis, metastatic mammal glands cancer expression profiling in humans and animals. Angiogenesis has been assessed by quantitative and immunohistochemical characteristics by means of evaluation of microvascular density (MVD using Claudin-5 (CLDN-5 as a marker of vascular endothelium in tumors of mammary glands in dogs.

  6. Lesions of anogenital mammary-like glands: an update.

    Science.gov (United States)

    Kazakov, Dmitry V; Spagnolo, Dominic V; Kacerovska, Denisa; Michal, Michal

    2011-01-01

    Long considered to be ectopic breast tissue representing the caudal remnants of the milk ridges, anogenital mammary-like glands are nowadays thought to represent a normal constituent of the anogenital area. Lesions involving these glands, benign or malignant, epithelial or stromal manifest a striking similarity to their mammary counterparts. This review addresses the recent literature on lesions of anogenital mammary-like glands and our personal experience with various lesions related to these structures. Discussed are the normal anatomy and histology of these glands as well as the clinical presentation, histopathological and immunohistochemical features, molecular biological aspects, and differential diagnosis of various lesions involving anogenital mammary-like glands, including lactating adenoma, hidradenoma papilliferum, hidradenocarcinoma papilliferum, fibroadenomas, phyllodes tumor, pseudoangiomatous stromal hyperplasia, extramammary Paget disease, and other carcinomas. In addition, "nonspecific" epithelial or stromal changes some of which can be likened to similar changes occurring in a range of benign breast disease, including sclerosing adenosis, columnar cell lesions, ductal lesions and various metaplastic changes affecting epithelium and myoepithelium are discussed. Although lesions of anogenital mammary-like glands are often discussed in many dermatopathology textbooks in the context of cutaneous adnexal neoplasms we advocate that the best approach to the diagnosis of these lesions is to relate them to analogous well recognized lesions occurring in the breast, that is, through the eyes of a breast pathologist. This will enable their recognition, precise classification and should introduce greater uniformity in how they are reported in the literature so that more meaningful clinicopathological comparisons and correlations may be made.

  7. The role of tight junctions in mammary gland function.

    Science.gov (United States)

    Stelwagen, Kerst; Singh, Kuljeet

    2014-03-01

    Tight junctions (TJ) are cellular structures that facilitate cell-cell communication and are important in maintaining the three-dimensional structure of epithelia. It is only during the last two decades that the molecular make-up of TJ is becoming unravelled, with two major transmembrane-spanning structural protein families, called occludin and claudins, being the true constituents of the TJ. These TJ proteins are linked via specific scaffolding proteins to the cell's cytoskeleton. In the mammary gland TJ between adjacent secretory epithelial cells are formed during lactogenesis and are instrumental in establishing and maintaining milk synthesis and secretion, whereas TJ integrity is compromised during mammary involution and also as result of mastitis and periods of mammary inflamation (including mastitis). They prevent the paracellular transport of ions and small molecules between the blood and milk compartments. Formation of intact TJ at the start of lactation is important for the establishment of the lactation. Conversely, loss of TJ integrity has been linked to reduced milk secretion and mammary function and increased paracellular transport of blood components into the milk and vice versa. In addition to acting as a paracellular barrier, the TJ is increasingly linked to playing an active role in intracellular signalling. This review focusses on the role of TJ in mammary function of the normal, non-malignant mammary gland, predominantly in ruminants, the major dairy producing species.

  8. Radix bupleuri Extract Inhibits Hyperplasia of Mammary Gland in Rats

    African Journals Online (AJOL)

    Purpose: To investigate the effect of Radix bupleuri extract (RBE) on hyperplasia of mammary gland (HMG) in rats. Methods: Forty virgin female Wistar rats were randomly divided into control, HMG model, positive control (Rupisanjie capsule, RPSJC), and low-, middle-, and high-dose RBE groups. Estrogen and ...

  9. Induction of mammary gland tumor in female Sprague- Dawley rats ...

    African Journals Online (AJOL)

    Evaluation of blood enzymes showed significantly higher (P < 0.005) serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in tumor-bearing than in normal rats. This LA7 cell-induced rat mammary gland tumor model may be useful for studies in breast cancer drug or nutraceutical research and development.

  10. Epidermal growth factor in mammary glands and milk from rats

    DEFF Research Database (Denmark)

    Thulesen, J; Raaberg, Lasse; Nexø, Ebba

    1993-01-01

    Epidermal growth factor (EGF) is one of the major growth-promoting agents in milk. Using immunohistochemistry we localized EGF in the mammary glands of lactating rats to the luminal border of the secretory cells. Following proteolytic pretreatment of the histological sections, the EGF...

  11. Bovine Mammary Gene Expression Profiling during the Onset of Lactation

    Science.gov (United States)

    Gao, Yuanyuan; Lin, Xueyan; Shi, Kerong; Yan, Zhengui; Wang, Zhonghua

    2013-01-01

    Background Lactogenesis includes two stages. Stage I begins a few weeks before parturition. Stage II is initiated around the time of parturition and extends for several days afterwards. Methodology/Principal Findings To better understand the molecular events underlying these changes, genome-wide gene expression profiling was conducted using digital gene expression (DGE) on bovine mammary tissue at three time points (on approximately day 35 before parturition (−35 d), day 7 before parturition (−7 d) and day 3 after parturition (+3 d)). Approximately 6.2 million (M), 5.8 million (M) and 6.1 million (M) 21-nt cDNA tags were sequenced in the three cDNA libraries (−35 d, −7 d and +3 d), respectively. After aligning to the reference sequences, the three cDNA libraries included 8,662, 8,363 and 8,359 genes, respectively. With a fold change cutoff criteria of ≥2 or ≤−2 and a false discovery rate (FDR) of ≤0.001, a total of 812 genes were significantly differentially expressed at −7 d compared with −35 d (stage I). Gene ontology analysis showed that those significantly differentially expressed genes were mainly associated with cell cycle, lipid metabolism, immune response and biological adhesion. A total of 1,189 genes were significantly differentially expressed at +3 d compared with −7 d (stage II), and these genes were mainly associated with the immune response and cell cycle. Moreover, there were 1,672 genes significantly differentially expressed at +3 d compared with −35 d. Gene ontology analysis showed that the main differentially expressed genes were those associated with metabolic processes. Conclusions The results suggest that the mammary gland begins to lactate not only by a gain of function but also by a broad suppression of function to effectively push most of the cell's resources towards lactation. PMID:23990904

  12. Bovine mammary gene expression profiling during the onset of lactation.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Gao

    Full Text Available BACKGROUND: Lactogenesis includes two stages. Stage I begins a few weeks before parturition. Stage II is initiated around the time of parturition and extends for several days afterwards. METHODOLOGY/PRINCIPAL FINDINGS: To better understand the molecular events underlying these changes, genome-wide gene expression profiling was conducted using digital gene expression (DGE on bovine mammary tissue at three time points (on approximately day 35 before parturition (-35 d, day 7 before parturition (-7 d and day 3 after parturition (+3 d. Approximately 6.2 million (M, 5.8 million (M and 6.1 million (M 21-nt cDNA tags were sequenced in the three cDNA libraries (-35 d, -7 d and +3 d, respectively. After aligning to the reference sequences, the three cDNA libraries included 8,662, 8,363 and 8,359 genes, respectively. With a fold change cutoff criteria of ≥ 2 or ≤-2 and a false discovery rate (FDR of ≤ 0.001, a total of 812 genes were significantly differentially expressed at -7 d compared with -35 d (stage I. Gene ontology analysis showed that those significantly differentially expressed genes were mainly associated with cell cycle, lipid metabolism, immune response and biological adhesion. A total of 1,189 genes were significantly differentially expressed at +3 d compared with -7 d (stage II, and these genes were mainly associated with the immune response and cell cycle. Moreover, there were 1,672 genes significantly differentially expressed at +3 d compared with -35 d. Gene ontology analysis showed that the main differentially expressed genes were those associated with metabolic processes. CONCLUSIONS: The results suggest that the mammary gland begins to lactate not only by a gain of function but also by a broad suppression of function to effectively push most of the cell's resources towards lactation.

  13. Mammary gland specific knockdown of the physiological surge in Cx26 during lactation retains normal mammary gland development and function.

    Directory of Open Access Journals (Sweden)

    Michael K G Stewart

    Full Text Available Connexin26 (Cx26 is the major Cx protein expressed in the human mammary gland and is up-regulated during pregnancy while remaining elevated throughout lactation. It is currently unknown if patients with loss-of-function Cx26 mutations that result in hearing loss and skin diseases have a greater susceptibility to impaired breast development. To investigate if Cx26 plays a critical role in mammary gland development and differentiation, a novel Cx26 conditional knockout mouse model was generated by crossing Cx26fl/fl mice with mice expressing Cre under the β-Lactoglobulin promoter. Conditional knockdown of Cx26 from the mammary gland resulted in a dramatic reduction in detectable gap junction plaques confirmed by a significant ∼65-70% reduction in Cx26 mRNA and protein throughout parturition and lactation. Interestingly, this reduction was accompanied by a decrease in mammary gland Cx30 gap junction plaques at parturition, while no change was observed for Cx32 or Cx43. Whole mount, histological and immunofluorescent assessment of breast tissue revealed comparatively normal lobuloalveolar development following pregnancy in the conditionally knockdown mice compared to control mice. In addition, glands from genetically-modified mice were capable of producing milk proteins that were evident in the lumen of alveoli and ducts at similar levels as controls, suggesting normal gland function. Together, our results suggest that low levels of Cx26 expression throughout pregnancy and lactation, and not the physiological surge in Cx26, is sufficient for normal gland development and function.

  14. The mammary gland-specific marsupial ELP and eutherian CTI share a common ancestral gene

    Directory of Open Access Journals (Sweden)

    Pharo Elizabeth A

    2012-06-01

    Full Text Available Abstract Background The marsupial early lactation protein (ELP gene is expressed in the mammary gland and the protein is secreted into milk during early lactation (Phase 2A. Mature ELP shares approximately 55.4% similarity with the colostrum-specific bovine colostrum trypsin inhibitor (CTI protein. Although ELP and CTI both have a single bovine pancreatic trypsin inhibitor (BPTI-Kunitz domain and are secreted only during the early lactation phases, their evolutionary history is yet to be investigated. Results Tammar ELP was isolated from a genomic library and the fat-tailed dunnart and Southern koala ELP genes cloned from genomic DNA. The tammar ELP gene was expressed only in the mammary gland during late pregnancy (Phase 1 and early lactation (Phase 2A. The opossum and fat-tailed dunnart ELP and cow CTI transcripts were cloned from RNA isolated from the mammary gland and dog CTI from cells in colostrum. The putative mature ELP and CTI peptides shared 44.6%-62.2% similarity. In silico analyses identified the ELP and CTI genes in the other species examined and provided compelling evidence that they evolved from a common ancestral gene. In addition, whilst the eutherian CTI gene was conserved in the Laurasiatherian orders Carnivora and Cetartiodactyla, it had become a pseudogene in others. These data suggest that bovine CTI may be the ancestral gene of the Artiodactyla-specific, rapidly evolving chromosome 13 pancreatic trypsin inhibitor (PTI, spleen trypsin inhibitor (STI and the five placenta-specific trophoblast Kunitz domain protein (TKDP1-5 genes. Conclusions Marsupial ELP and eutherian CTI evolved from an ancestral therian mammal gene before the divergence of marsupials and eutherians between 130 and 160 million years ago. The retention of the ELP gene in marsupials suggests that this early lactation-specific milk protein may have an important role in the immunologically naïve young of these species.

  15. Autocrine-paracrine regulation of the mammary gland.

    Science.gov (United States)

    Weaver, S R; Hernandez, L L

    2016-01-01

    The mammary gland has a remarkable capacity for regulation at a local level, particularly with respect to its main function: milk secretion. Regulation of milk synthesis has significant effects on animal and human health, at the level of both the mother and the neonate. Control by the mammary gland of its essential function, milk synthesis, is an evolutionary necessity and is therefore tightly regulated at a local level. For at least the last 60 yr, researchers have been interested in elucidating the mechanisms underpinning the mammary gland's ability to self-regulate, largely without the influence from systemic hormones or signals. By the 1960s, scientists realized the importance of milk removal in the capacity of the gland to produce milk and that the dynamics of this removal, including emptying of the alveolar spaces and frequency of milking, were controlled locally as opposed to traditional systemic hormonal regulation. Using both in vitro systems and various mammalian species, including goats, marsupials, humans, and dairy cows, it has been demonstrated that the mammary gland is largely self-regulating in its capacity to support the young, which is the evolutionary basis for milk production. Local control occurs at the level of the mammary epithelial cell through pressure and stretching negative-feedback mechanisms, and also in an autocrine fashion through bioactive factors within the milk which act as inhibitors, regulating milk secretion within the alveoli themselves. It is only within the last 20 to 30 yr that potential candidates for these bioactive factors have been examined at a molecular level. Several, including parathyroid hormone-related protein, growth factors (transforming growth factor, insulin-like growth factor, epidermal growth factor), and serotonin, are synthesized within and act upon the gland and possess dynamic receptor activity resulting in diverse effects on growth, calcium homeostasis, and milk composition. This review will focus on the

  16. Increase in biofilm formation by Escherichia coli under conditions that mimic the mastitic mammary gland

    Directory of Open Access Journals (Sweden)

    João Carlos Miguel Costa

    2014-04-01

    Full Text Available Bacterial biofilms are involved in the aggravation and recurrence of clinical mastitis in dairy herds. Several factors such as pH, temperature, concentration of O2 and glucose can affect their induction and growth rates. In this study, biofilm production was demonstrated by 27 Escherichia coli strains isolated from bovine mastitis at different pH values depending on the availability of glucose, mimicking conditions found in mammary glands affected by the disease. Biofilm formation was analyzed by spectrophotometric analysis in microtiter plate with 16 different culture media and by scanning electron microscopy. Biofilm formation was greater in isolates cultured under conditions associated with low glucose availability (0.5% or 1.5% and with either an acidic (5.5 or alkaline (8.5 pH, compared to conditions associated with high glucose availability (2.5% or 3.5% and near-neutral pH (6.5 or 7.5. Results indicate possible favoring of biofilm production in the later stages of the infectious process caused by E. coli, when the gland environment is less propitious to bacterial growth due to the stress conditions mentioned above; contrasting with the environment of the healthy mammary gland, in which there is no limitation on nutrients or conditions of particular alkalinity or acidity. Thus, knowledge of the stage in which is the infection and environmental conditions of the mammary gland that cause increased production of biofilms is of paramount importance to guide the most appropriate control strategies to prevent relapse after treatment of bovine mastitis, an economically important disease in dairy cattle worldwide.

  17. Biofilm mediates Enterococcus faecalis adhesion, invasion and survival into bovine mammary epithelial cells.

    Science.gov (United States)

    Elhadidy, M; Zahran, E

    2014-03-01

    We proposed in this study that during intramammary infection, biofilm formation may facilitate adherence and colonization of Enterococcus faecalis to mammary gland epithelium. This was established by comparing six different Ent. faecalis isolates with different biofilm-forming profiles for their adhesive, invasive and survival capabilities to bovine mammary epithelial cell line (MAC-T). Our results showed increased ability of the biofilm-producer Ent. faecalis strains to adhere, invade and survive inside MAC-T cells rather than nonbiofilm-producer strains. We showed that growth of bacteria in bovine milk significantly augmented the adherence and invasion of all tested strains, and this feature was abolished again when strains were subcultured in brain heart infusion broth. Moreover, growth in bovine milk significantly increased biofilm formation by all tested strains. These results indicated that biofilm formation by Ent. faecalis, especially after expressing milk-dependent induction, may have special relevance in the pathogenesis of Ent. faecalis mastitis during intramammary infection by enhancing bovine mammary epithelial adhesion and colonization. Results obtained from current work highlighted the role of biofilm in the pathogenesis of Enterococcus faecalis mastitis. Those biofilm-forming strains might be substantial as useful antigens in diagnostic assays and as future vaccine candidates to control Ent. faecalis mastitis. © 2013 The Society for Applied Microbiology.

  18. The mammary gland and the homeobox gene Otx1.

    Science.gov (United States)

    Pagani, Ilaria S; Terrinoni, Alessandro; Marenghi, Laura; Zucchi, Ileana; Chiaravalli, Anna M; Serra, Valeria; Rovera, Francesca; Sirchia, Silvia; Dionigi, Gianlorenzo; Miozzo, Monica; Mozzo, Monica; Frattini, Annalisa; Ferrari, Alberta; Capella, Carlo; Pasquali, Francesco; Lo Curto, Francesco; Curto, Francesco L; Albertini, Alberto; Melino, Gerry; Porta, Giovanni

    2010-01-01

    The mammary gland, the unique organ that primarily form at puberty, is an ideal model to study the functions of homeobox (HB) genes in both development and tumorigenesis. HB genes comprise a large family of developmental regulators that have a critical role in cell growth and differentiation. In the normal mammary gland, homeobox genes are involved in ductal formation, epithelial branching, and lobulo-alveolar development by regulating epithelial proliferation and differentiation. The HB genes are controlled in a spatial and temporal manner in both stromal and epithelial cells. They are coordinately regulated by hormones and extracellular matrix, suggesting that many signaling pathways are involved in homeobox gene functions. When homeobox genes are misexpressed in animal models, different defects are displayed in mammary gland development. Aberrant expression of homeobox genes, overexpressed or downregulated, is found in primary carcinomas and in breast cancer. The Otx1 HB gene is a classic regulatory of nervous system development during embryogenesis. Postnatally Otx1 is transcribed in the anterior pituitary gland, where activates transcription of the pituitary hormones, and plays a role in hematopoiesis, enhancing pluripotent cells, and erythroid differentiation. Otx1 can still be detected in mature cells of the erythroid and megacaryocytic lineage. During cyclical development of mammary gland, the Otx1 gene is overexpressed in lactation, confirming a role of this transcription factor in cell differentiation. Recent studies report that Otx1 is overexpressed in breast cancer. Otx1 is expressed during embryogenesis, and it is expressed again during carcinogenesis, implying its possible function in differentiation of neoplastic cells. © 2010 Wiley Periodicals, Inc.

  19. Mammary Gland Reprogramming: Metalloproteinases Couple Form with Function

    Science.gov (United States)

    Khokha, Rama; Werb, Zena

    2011-01-01

    The adult mammary structure provides for the rapid growth, development, and immunological protection of the live-born young of mammals through its production of milk. The dynamic remodeling of the branched epithelial structure of the mammary gland in response to physiological stimuli that allow its programmed branching morphogenesis at puberty, cyclical turnover during the reproductive cycle, differentiation into a secretory organ at parturition, postlactational involution, and ultimately, regression with age is critical for these processes. Extracellular metalloproteinases are essential for the remodeling programs that operate in the tissue microenvironment at the interface of the epithelium and the stroma, coupling form with function. Deregulated proteolytic activity drives the transition of a physiological mammary microenvironment into a tumor microenvironment, facilitating malignant transformation. PMID:21106646

  20. Modeling and analysis of transport in the mammary glands

    Science.gov (United States)

    Quezada, Ana; Vafai, Kambiz

    2014-08-01

    The transport of three toxins moving from the blood stream into the ducts of the mammary glands is analyzed in this work. The model predictions are compared with experimental data from the literature. The utility of the model lies in its potential to improve our understanding of toxin transport as a pre-disposing factor to breast cancer. This work is based on a multi-layer transport model to analyze the toxins present in the breast milk. The breast milk in comparison with other sampling strategies allows us to understand the mass transport of toxins once inside the bloodstream of breastfeeding women. The multi-layer model presented describes the transport of caffeine, DDT and cimetidine. The analysis performed takes into account the unique transport mechanisms for each of the toxins. Our model predicts the movement of toxins and/or drugs within the mammary glands as well as their bioaccumulation in the tissues.

  1. Invasive ductal carcinoma of the mammary gland in a mare.

    Science.gov (United States)

    Hirayama, K; Honda, Y; Sako, T; Okamoto, M; Tsunoda, N; Tagami, M; Taniyama, H

    2003-01-01

    A 21-year-old thoroughbred mare had a 35 x 14 x 10 cm mass involving the mammary gland. Metastases were found in the kidneys, lungs, skeletal muscles, and regional lymph nodes. Histopathologic examination of the tumor revealed a ductal solid carcinoma with extensive intraductal and intralobular involvement and focal infiltration of the adjacent stroma. The intralobular neoplasms were divided into irregularly shaped islands and sheets of polygonal and spindle-shaped epithelial cells by thick or thin fibrous connective tissue bundles. The neoplastic cells had a small or moderate amount of cytoplasm that stained faintly with eosin and round or oval hyperchromatic nuclei. Immunohistochemically, the neoplastic cells were strongly positive for Lu-5, weakly positive for AE1/AE3, vimentin, and glial fibrillary acidic protein, and negative for cytokeratin 8, cytokeratin 14, alpha-smooth muscle actin, calponin, and S100. The neoplasm was diagnosed as an invasive ductal carcinoma of the mammary gland with multiple metastases.

  2. MAMMARY GLAND ADENOCARCINOMA IN A MALE BORNEAN ORANGUTAN (PONGO PYGMAEUS).

    Science.gov (United States)

    Carpenter, Nancy A; Crook, Erika K

    2017-03-01

    An adult male Bornean orangutan ( Pongo pygmaeus ) was diagnosed with invasive, poorly differentiated grade 9/9 mammary gland adenocarcinoma from a subcutaneous mass that was surgically removed during a routine preventative health examination. The tumor was tested for estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and HER2 fluorescence in situ hybridization (HER2 FISH). Whole blood was tested for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. The orangutan was treated orally with two common human breast cancer drugs; tamoxifen and anastrozole. The orangutan lived for 4.5 yr postdetection, dying from an unrelated cause. This is the first reported case of mammary gland adenocarcinoma in a male great ape.

  3. Nasopharyngeal carcinoma metastasis to the mammary gland: A case report.

    Science.gov (United States)

    Li, Shuang; Yang, Jiyuan

    2015-01-01

    Nasopharyngeal carcinoma is the second most common type of malignancy in Southern China. Metastatic sites are usually multifocal and involve the bones, lungs and distant lymph nodes. To date, there have been no studies with regard to nasopharyngeal carcinoma metastasis to the mammary gland. In the current study, the case of a 56-year-old female with nasal obstruction, epitaxis and a bilateral neck mass is presented. Following a series of examinations, the patient was diagnosed with nasopharyngeal carcinoma (cT3N3M0). Subsequently, the patient received radical radiation therapy. After three months, a mass was identified in the left breast, together with enlargement of multiple lymph nodes in the left axilla. The patient underwent a mastectomy and pathological examination revealed that the breast mass and axillary lymph node tissues were derived from the nasopharynx. To the best of our knowledge, this is the first report of a nasopharyngeal carcinoma that metastasized to the mammary gland.

  4. Mammary gland tumor formation in transgenic mice overexpressing stromelysin-1

    Energy Technology Data Exchange (ETDEWEB)

    Sympson, Carolyn J; Bissell, Mina J; Werb, Zena

    1995-06-01

    An intact basement membrane (BM) is essential for the proper function, differentiation and morphology of many epithelial cells. The disruption or loss of this BM occurs during normal development as well as in the disease state. To examine the importance of BM during mammary gland development in vivo, we generated transgenic mice that inappropriately express autoactivating isoforms of the matrix metalloproteinase stromelysin-1. The mammary glands from these mice are both functionally and morphologically altered throughout development. We have now documented a dramatic incidence of breast tumors in several independent lines of these mice. These data suggest that overexpression of stromelysin-1 and disruption of the BM may be a key step in the multi-step process of breast cancer.

  5. [Mammary analog secretory carcinoma of the parotid gland].

    Science.gov (United States)

    Guérin, Maxime; Diedhiou, Abdoulaye; Nallet, Emmanuel; Duflo, Suzy; Laé, Marick; Wassef, Michel

    2014-10-01

    Mammary analog secretory carcinoma (MASC) of the parotid gland is a rare and recently described lesion. We report the case of a 46-year-old man with a tumor of the parotid gland which was carried to the diagnosis of MASC. Diagnostic was confirmed by highlighting the ETV6-NTRK3 gene translocation. However, some morphologic and immunohistochemical features are suggestive of this entity. This carcinoma should be distinguished from its main differential diagnoses: acinic cell carcinoma and low grade cribriform cystadenocarcinoma. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. The male mammary gland: a target for the xenoestrogen bisphenol A.

    Science.gov (United States)

    Vandenberg, Laura N; Schaeberle, Cheryl M; Rubin, Beverly S; Sonnenschein, Carlos; Soto, Ana M

    2013-06-01

    Males of some strains of mice retain their mammary epithelium even in the absence of nipples. Here, we have characterized the mammary gland in male CD-1 mice both in whole mounts and histological sections. We also examined the effects of bisphenol A (BPA), an estrogen mimic that alters development of the female mouse mammary gland. BPA was administered at a range of environmentally relevant doses (0.25-250μg/kg/day) to pregnant and lactating mice and then the mammary glands of male offspring were examined at several periods in adulthood. We observed age- and dose-specific effects on mammary gland morphology, indicating that perinatal BPA exposures alter the male mammary gland in adulthood. These results may provide insight into gynecomastia, the most common male breast disease in humans, where proliferation of the mammary epithelium leads to breast enlargement. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Morphogenesis of Mammary Glands in Buffalo (Bubalus bubalis

    Directory of Open Access Journals (Sweden)

    Amit Challana

    2014-01-01

    Full Text Available The present research was elucidated on the morphogenesis of mammary gland of buffalo during prenatal development. Total of 16 foetuses ranging from 1.2 cm (34 days to 108 cm CVRL (curved crown rump length (317 days were used for study. The study revealed that mammary line was first observed at 1.2 cm CVRL (34 days, mammary hillock at 1.7 cm (37 days, and mammary bud at 2.6 cm CVRL (41 days foetuses. Epidermal cone was found at 6.7 cm CVRL (58 days whereas primary and secondary ducts were observed at 7.4 cm CVRL (62 days and 15 cm CVRL (96 days, respectively. Connective tissue whorls were reported at 18.2 cm CVRL (110 days and internal elastic lamina and muscle layers at 24.1 cm CVRL (129 days. Lobules were observed at 29.3 cm CVRL (140 days, rosette of furstenberg at 39.5 cm CVRL (163 days, and keratin plug at 45.5 cm CVRL (176 days foetus. Primordia of sweat and sebaceous glands around hair follicle were seen at 21.2 cm CVRL (122 days of foetal life. Differentiation of all the skin layers along with cornification was observed at 69 cm (229 days in group III foetuses.

  8. Ultrastructure of the human mammary gland. II. Postpartum lactogenesis.

    Science.gov (United States)

    Tobon, H; Salazar, H

    1975-05-01

    The history and fine structure of 7 human mammary glands were studied in the post partum. Widespread hypertrophy and hyperplasia of the mammary acini were observed accompanied by dilatation and engorgement of the lumen by milk. Loose strands of connective tissue surrounding the mammary lobules and ductules contained dilated, engorged vascular channels. The lactogenic epithelial cells displayed rich cytoplasm containing prominent layering stacks of rough endoplasmic reticulum closely related to the enlarged oval mitochondria, on occasion surrounding their entire circumference. Also noted were numerous ribosomes and polyribosomes. The markedly hypertrophied golgi apparatus revealed cisternae containing particulate electron dense material and vesicles with dense granules. The latter were frequently seen being discharged in the lumen devoid of limiting membrane. Abundant fat droplets were present in the basal and apical regions and "pinched off" into the lumen, apparently surrounded by a limiting membrane. The lactogenic cells were richly endowed with slender microvilli in their luminal pole and related to one another by cytoplasmic prolongations, desmosomes and tight junctions. The myoepithelium was stretched and thinned out toward the periphery of the acini between the lactogenic epithelium and the basement lamina. Abundant myofilaments were present in the myoepithelial cells. Pinocytotic vesicles were also present, although not very numerous, in both the lactogenic and the myoepithelial cells. In general the human mammary gland during lactopoiesis follows similar structural changes as those previously described in other mammals.

  9. Construction of mammary gland specific expression plasmid pIN ...

    African Journals Online (AJOL)

    The backbone plasmid pBC1 contained goat β-casein 5′ arm and β-casein 3′ arm, to target mammary gland-specific gene expression. First, the igf-1 gene was cloned from liver tissue harvested from a Saanen dairy goat and inserted downstream of the β-casein 5' arm. Then the neo gene was amplified from plasmid ...

  10. Nasopharyngeal carcinoma metastasis to the mammary gland: A case report

    OpenAIRE

    Li, Shuang; Yang, Jiyuan

    2014-01-01

    Nasopharyngeal carcinoma is the second most common type of malignancy in Southern China. Metastatic sites are usually multifocal and involve the bones, lungs and distant lymph nodes. To date, there have been no studies with regard to nasopharyngeal carcinoma metastasis to the mammary gland. In the current study, the case of a 56-year-old female with nasal obstruction, epitaxis and a bilateral neck mass is presented. Following a series of examinations, the patient was diagnosed with nasopharyn...

  11. Automatic segmentation of histological structures in mammary gland tissue sections

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Gonzalez, Rodrigo; Deschamps, Thomas; Idica, Adam K.; Malladi, Ravikanth; Ortiz de Solorzano, Carlos

    2004-02-17

    Real-time three-dimensional (3D) reconstruction of epithelial structures in human mammary gland tissue blocks mapped with selected markers would be an extremely helpful tool for breast cancer diagnosis and treatment planning. Besides its clear clinical application, this tool could also shed a great deal of light on the molecular basis of breast cancer initiation and progression. In this paper we present a framework for real-time segmentation of epithelial structures in two-dimensional (2D) images of sections of normal and neoplastic mammary gland tissue blocks. Complete 3D rendering of the tissue can then be done by surface rendering of the structures detected in consecutive sections of the blocks. Paraffin embedded or frozen tissue blocks are first sliced, and sections are stained with Hematoxylin and Eosin. The sections are then imaged using conventional bright field microscopy and their background is corrected using a phantom image. We then use the Fast-Marching algorithm to roughly extract the contours of the different morphological structures in the images. The result is then refined with the Level-Set method which converges to an accurate (sub-pixel) solution for the segmentation problem. Finally, our system stacks together the 2D results obtained in order to reconstruct a 3D representation of the entire tissue block under study. Our method is illustrated with results from the segmentation of human and mouse mammary gland tissue samples.

  12. Role of T-Box Gene in Mammary Gland Development and Neoplasia

    Science.gov (United States)

    1998-08-01

    Mammary Gland Development and Neoplasia PRINCIPAL INVESTIGATION: Virginia Papaioannou, Ph.D. CONTRACTING ORGANIZATION: Columbia University New York...of T-box Gene in Mammary Gland Development and Neoplasia DAMD17-96-1-6090 6. AUTHOR(S) Virginia E. Papaioannou, Ph.D. 7. PERFORMING ORGANIZATION NAME...hypothesis is that Tbx2 and TMx3 are required in the signalling pathway of nomal mammary gland development, and could also be involved in neoplasia

  13. Characterization of the Six1 homeobox gene in normal mammary gland morphogenesis

    Directory of Open Access Journals (Sweden)

    McManaman James L

    2010-01-01

    Full Text Available Abstract Background The Six1 homeobox gene is highly expressed in the embryonic mammary gland, continues to be expressed in early postnatal mammary development, but is lost when the mammary gland differentiates during pregnancy. However, Six1 is re-expressed in breast cancers, suggesting that its re-instatement in the adult mammary gland may contribute to breast tumorigenesis via initiating a developmental process out of context. Indeed, recent studies demonstrate that Six1 overexpression in the adult mouse mammary gland is sufficient for initiating invasive carcinomas, and that its overexpression in xenograft models of mammary cancer leads to metastasis. These data demonstrate that Six1 is causally involved in both breast tumorigenesis and metastasis, thus raising the possibility that it may be a viable therapeutic target. However, because Six1 is highly expressed in the developing mammary gland, and because it has been implicated in the expansion of mammary stem cells, targeting Six1 as an anti-cancer therapy may have unwanted side effects in the breast. Results We sought to determine the role of Six1 in mammary development using two independent mouse models. To study the effect of Six1 loss in early mammary development when Six1 is normally expressed, Six1-/- embryonic mammary glands were transplanted into Rag1-/- mice. In addition, to determine whether Six1 downregulation is required during later stages of development to allow for proper differentiation, we overexpressed Six1 during adulthood using an inducible, mammary-specific transgenic mouse model. Morphogenesis of the mammary gland occurred normally in animals transplanted with Six1-/- embryonic mammary glands, likely through the redundant functions of other Six family members such as Six2 and Six4, whose expression was increased in response to Six1 loss. Surprisingly, inappropriate expression of Six1 in the adult mammary gland, when levels are normally low to absent, did not inhibit

  14. Perinatal ethinyl oestradiol alters mammary gland development in male and female Wistar rats

    DEFF Research Database (Denmark)

    Mandrup, Karen; Hass, Ulla; Christiansen, Sofie

    2012-01-01

    Increased attention is being paid to human mammary gland development because of concerns for environmental influences on puberty onset and breast cancer development. Studies in rodents have showed a variety of changes in the mammary glands after perinatal exposure to endocrine disrupting chemicals......, Wistar rats were exposed to 0, 5, 15 or 50 μg/kg of ethinyl oestradiol per day during gestation and lactation. A wide range of morphological parameters were evaluated in whole mounts of mammary glands from male and female offspring PD21–22. This study showed that in both male and female pre...... exposures may alter mammary gland development, disrupt lactation and alter susceptibility to breast cancer....

  15. New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells.

    Science.gov (United States)

    Chang, Ted H-T; Kunasegaran, Kamini; Tarulli, Gerard A; De Silva, Duvini; Voorhoeve, P Mathijs; Pietersen, Alexandra M

    2014-01-07

    Parity-identified mammary epithelial cells (PI-MECs) are an interesting cellular subset because they survive involution and are a presumptive target for transformation by human epidermal growth factor receptor 2 (HER2)/neu in mammary tumors. Depending on the type of assay, PI-MECs have been designated lobule-restricted progenitors or multipotent stem/progenitor cells. PI-MECs were reported to be part of the basal population of mammary epithelium based on flow cytometry. We investigated the cellular identity and lineage potential of PI-MECs in intact mammary glands. We performed a quantitative and qualitative analysis of the contribution of PI-MECs to mammary epithelial cell lineages in pregnant and involuted mammary glands by immunohistochemistry, fluorescence-activated cells sorting (FACS), and quantitative polymerase chain reaction. PI-MECs were labeled by the activation of Whey Acidic Protein (WAP)-Cre during pregnancy that results in permanent expression of yellow fluorescent protein. After involution, PI-MECs are present exclusively in the luminal layer of mammary ducts. During pregnancy, PI-MECs contribute to the luminal layer but not the basal layer of alveolar lobules. Strikingly, whereas all luminal estrogen receptor (ER)-negative cells in an alveolus can be derived from PI-MECs, the alveolar ER-positive cells are unlabeled and reminiscent of Notch2-traced L cells. Notably, we observed a significant population of unlabeled alveolar progenitors that resemble PI-MECs based on transcriptional and histological analysis. Our demonstration that PI-MECs are luminal cells underscores that not only basal cells display multi-lineage potential in transplantation assays. However, the lineage potential of PI-MECs in unperturbed mammary glands is remarkably restricted to luminal ER-negative cells of the secretory alveolar lineage. The identification of an unlabeled but functionally similar population of luminal alveolar progenitor cells raises the question of whether PI

  16. Relationship between histology, development and tumorigenesis of mammary gland in female rat

    Science.gov (United States)

    LÍŠKA, Ján; BRTKO, Július; DUBOVICKÝ, Michal; MACEJOVÁ, Dana; KISSOVÁ, Viktória; POLÁK, Štefan; UJHÁZY, Eduard

    2015-01-01

    The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer. An early first full-term pregnancy may have a protective effect. Rodent models are useful for investigating potential breast carcinogens. The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential. PMID:26424555

  17. Mammary gland morphology in Sprague-Dawley rats following treatment with an organochlorine mixture in utero and neonatal genistein

    National Research Council Canada - National Science Library

    Foster, Warren G; Younglai, Edward V; Boutross-Tadross, Odette; Hughes, Claude L; Wade, Michael G

    ... of thoracic mammary glands was observed in female offspring at 200 days of age. Therefore, the objective of this study was to analyze the effect of in utero exposure to a mixture of toxicants on mammary gland morphology...

  18. Developmental Expression of Claudins in the Mammary Gland.

    Science.gov (United States)

    Baumgartner, Heidi K; Rudolph, Michael C; Ramanathan, Palaniappian; Burns, Valerie; Webb, Patricia; Bitler, Benjamin G; Stein, Torsten; Kobayashi, Ken; Neville, Margaret C

    2017-06-01

    Claudins are a large family of membrane proteins whose classic function is to regulate the permeability of tight junctions in epithelia. They are tetraspanins, with four alpha-helices crossing the membrane, two extracellular loops, a short cytoplasmic N-terminus and a longer and more variable C-terminus. The extracellular ends of the helices are known to undergo side-to-side (cis) interactions that allow the formation of claudin polymers in the plane of the membrane. The extracellular loops also engage in head-to-head (trans) interactions thought to mediate the formation of tight junctions. However, claudins are also present in intracellular structures, thought to be vesicles, with less well-characterized functions. Here, we briefly review our current understanding of claudin structure and function followed by an examination of changes in claudin mRNA and protein expression and localization through mammary gland development. Claudins-1, 3, 4, 7, and 8 are the five most prominent members of the claudin family in the mouse mammary gland, with varied abundance and intracellular localization during the different stages of post-pubertal development. Claudin-1 is clearly localized to tight junctions in mammary ducts in non-pregnant non-lactating animals. Cytoplasmic puncta that stain for claudin-7 are present throughout development. During pregnancy claudin-3 is localized both to the tight junction and basolaterally while claudin-4 is found only in sparse puncta. In the lactating mouse both claudin-3 and claudin-8 are localized at the tight junction where they may be important in forming the paracellular barrier. At involution and under challenge by lipopolysaccharide claudins -1, -3, and -4 are significantly upregulated. Claudin-3 is still colocalized with tight junction molecules but is also distributed through the cytoplasm as is claudin-4. These largely descriptive data provide the essential framework for future mechanistic studies of the function and regulation of

  19. The male mammary gland: a target for the xenoestrogen bisphenol A

    OpenAIRE

    Vandenberg, Laura N.; Schaeberle, Cheryl M.; Rubin, Beverly S.; Sonnenschein, Carlos; Soto, Ana M.

    2013-01-01

    Males of some strains of mice retain their mammary epithelium even in the absence of nipples. Here, we have characterized the mammary gland in male CD-1 mice both in whole mounts and histological sections. We also examined the effects of bisphenol A (BPA), an estrogen mimic that alters development of the female mouse mammary gland. BPA was administered at a range of environmentally relevant doses (0.25 – 250 μg/kg/day) to pregnant and lactating mice and then the mammary glands of male offspri...

  20. The Role of BRCA1 in Suppressing Epithelial Mesenchymal Transition in Mammary Gland and Tumor Development

    Science.gov (United States)

    2016-11-01

    pathology and expression of CK5 and CK14 in these samples with mouse mammary tumors. We noticed that both the tumor cell morphology and expression pattern...AWARD NUMBER: W81XWH-13-1-0282 TITLE: The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and Tumor...2013 - 31-AUG-2016 4. TITLE AND SUBTITLE The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and Tumor Development 5a

  1. Prototheca zopfii isolated from bovine mastitis induced oxidative stress and apoptosis in bovine mammary epithelial cells

    OpenAIRE

    Shahid, Muhammad; Gao, Jian; Zhou, Yanan; Liu, Gang; Ali, Tariq; Deng, Youtian; Sabir, Naveed; Su, Jingliang; Han, Bo

    2017-01-01

    Bovine protothecal mastitis results in considerable economic losses worldwide. However, Prototheca zopfii induced morphological alterations and oxidative stress in bovine mammary epithelial cells (bMECs) is not comprehensively studied yet. Therefore, the aim of this current study was to investigate the P. zopfii induced pathomorphological changes, oxidative stress and apoptosis in bMECs. Oxidative stress was assessed by evaluating catalase (CAT), superoxide dismutase (SOD), glutathione peroxi...

  2. Papillomatosis of the bovine teat (mammary papilla).

    Science.gov (United States)

    Olson, R O; Olson, C; Easterday, B C

    1982-12-01

    A 4th of 667 cattle examined at a Wisconsin abattoir had teat papillomas. Excised teat papillomas were sorted by gross morphologic characteristics into 3 groups: (i) atypical filiform, (ii) atypical flat, and (iii) typical fibropapilloma. Bovine papilloma virus capsid antigen was detected in thin-section slides of the 3 groups of teat papillomas by peroxidase-antiperoxidase assay. The bovine papilloma virus involved with the atypical papillomas could not be characterized by molecular hybridization, because enough pure virus could not be harvested. Homogenates of the 3 groups of teat papillomas were inoculated on 2 ponies and 4 calves. Typical fibropapillomas were produced on the 4 calves, and fibromas, on the 2 ponies. Atypical papillomas were produced only in 2 heifers.

  3. Premature mammary gland involution with repeated corticosterone injection in interleukin 10-deficient mice.

    Science.gov (United States)

    Hwang, Woo-Sung; Bae, Ji-Hyun; Yeom, Su-Cheong

    2016-12-01

    Recently, we found that maternal stress could induce premature mammary gland involution in interleukin 10 knock out (IL-10 -/- ) mice. To elucidate correlation between stress, IL-10, and mammary gland involution, corticosterone was injected into the lactating wild type and IL-10-deficient mice and assessed mammary gland phenotype. Repetitive corticosterone injection developed premature mammary gland involution only in B6.IL-10 -/- mice; moreover, it induced alopecia in nursing pups. Corticosterone injection induced several typical changes such as mammary gland epithelial cell apoptosis, macrophage infiltration, fat deposition in adipocyte, STAT3 phosphorylation, and upregulation of tyrosine hydroxylase gene in adrenal gland. Overall incidence of pup alopecia and mammary gland involution was relatively high in corticosterone than control B6.IL-10 -/- group (57% vs. 20%). Our finding demonstrates that IL-10 is important for stress modulation, and B6.Il-10 -/- with corticosterone has several advantage such as simple to establish, well-defined onset of mammary gland involution, high incidence, and inducing pup alopecia.

  4. Targeted expression of MDM2 uncouples S phase from mitosis and inhibits mammary gland development independent of p53.

    Science.gov (United States)

    Lundgren, K; Montes de Oca Luna, R; McNeill, Y B; Emerick, E P; Spencer, B; Barfield, C R; Lozano, G; Rosenberg, M P; Finlay, C A

    1997-03-15

    MDM2 is a cellular protein that binds to and inactivates the p53 tumor suppressor protein. Although mdm2 has been shown to function as an oncogene in vitro, all studies to date have assessed MDM2 activities in the presence of p53, implicating p53 inactivation in MDM2-directed transformation. To determine the role of MDM2 in the cell cycle and in tumorigenesis and whether or not this role is dependent on p53, an MDM2 minigene was expressed during gestation and lactation in the mammary gland of both wild-type p53 (p53+/+) and p53 knockout (p53-/-) mice using the bovine beta-lactoglobulin promoter. In six different transgenic mouse lines, deregulated expression of MDM2 inhibited normal development and morphogenesis of the mammary gland, and caused cellular hypertrophy and nuclear abnormalities. These abnormalities included both multinucleated cells and enlarged cells with giant nuclei. Although there were fewer epithelial cells present in the transgenic mammary gland, no apoptosis was observed. Instead, BrdU incorporation and PCNA staining showed that 12%-27% of the transgenic mammary epithelial cells were in S phase at a time when normal cells were terminally differentiated. Analysis of DNA content showed that 30%-45% of the cells were polyploid, with DNA contents up to 16N, indicating that overexpression of MDM2 caused mammary epithelial cells to undergo multiple rounds of S phase without cell division. This phenotype was similar in the p53+/+ and p53-/- background, demonstrating a role for MDM2 in the regulation of DNA synthesis that is independent of the ability of MDM2 to inhibit p53 activity. Additionally, multiple lines of BLGMDM2 transgenic mice developed mammary tumors, confirming that overproduction of MDM2 contributes to tumorigenesis in epithelial cells in vivo.

  5. Similarity of GATA-3 Expression between Rat and Human Mammary Glands.

    Science.gov (United States)

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; Shikata, Nobuaki; Tsubura, Airo

    2014-07-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. In particular, GATA-3 is necessary for mammary gland maturation and is a useful marker in the characterization of mammary carcinoma in humans. The expression of GATA-3 protein in normal mammary glands, fibroadenomas and carcinomas was immunohistochemically compared in female rats and humans. In normal mammary glands of rats and humans, scattered luminal cells in the acini and whole ductal epithelial cells were positive for GATA-3 in the nuclei. No positive cells were detected in rat or human fibroadenomas. In rat and human mammary carcinomas, the nuclei of proliferating luminal-derived cancer cells expressed GATA-3. Therefore, GATA-3 protein is a candidate marker for mammary carcinoma in rats as well as humans.

  6. Differential roles of ERα and ERβ in normal and neoplastic development in the mouse mammary gland.

    Science.gov (United States)

    Mehta, Rajendra G; Hawthorne, Michael; Mehta, Rajeshwari R; Torres, Karen E O; Peng, Xinjian; McCormick, David L; Kopelovich, Levy

    2014-01-01

    The present experiments were performed to determine the roles of estrogen receptors α and β (ERα and ERβ) in normal and neoplastic development in the mouse mammary gland. In wild-type mice, in vivo administration of estradiol (E) + progesterone (P) stimulated mammary ductal growth and alveolar differentiation. Mammary glands from mice in which the ERβ gene has been deleted (βERKO mice) demonstrated normal ductal growth and differentiation in response to E + P. By contrast, mammary glands from mice in which the ERα gene has been deleted (αERKO mice) demonstrated only rudimentary ductal structures that did not differentiate in response to E + P. EGF demonstrates estrogen-like activity in the mammary glands of αERKO mice: treatment of αERKO mice with EGF + P (without E) supported normal mammary gland development, induced expression of progesterone receptor (PR), and increased levels of G-protein-coupled receptor (GPR30) protein. Mammary gland development in βERKO mice treated with EGF + P was comparable to that of wild-type mice receiving EGF + P; EGF had no statistically significant effects on the induction of PR or expression of GPR30 in mammary glands harvested from either wild-type mice or βERKO mice. In vitro exposure of mammary glands to 7,12-dimethylbenz[a]anthracene (DMBA) induced preneoplastic mammary alveolar lesions (MAL) in glands from wild-type mice and βERKO mice, but failed to induce MAL in mammary glands from αERKO mice. Microarray analysis of DMBA-treated mammary glands identified 28 functional pathways whose expression was significantly different in αERKO mice versus both βERKO and wild-type mice; key functions that were differentially expressed in αERKO mice included cell division, cell proliferation, and apoptosis. The data demonstrate distinct roles for ERα and ERβ in normal and neoplastic development in the mouse mammary gland, and suggest that EGF can mimic the ERα-mediated effects of E in this organ.

  7. Mammary gland development in transgenic male mice expressing human P450 aromatase.

    Science.gov (United States)

    Li, Xiangdong; Wärri, Anni; Mäkelä, Sari; Ahonen, Tommi; Streng, Tomi; Santti, Risto; Poutanen, Matti

    2002-10-01

    We recently generated a transgenic mouse strain that expresses the human aromatase gene under the ubiquitin C promoter (AROM+). We have previously shown that in these mice the serum estradiol concentration is highly elevated, whereas the testosterone concentration is decreased. In the present study we examined mammary gland development in AROM+ male mice at different ages and found that the mammary glands of AROM+ males undergo ductal and alveolar development morphologically resembling that of terminally differentiated female mammary glands, expressing mRNA for a milk protein gene (beta-casein). The male mammary glands also express multiple hormone receptors typical for female mammary gland: estrogen receptor alpha and beta, progesterone receptor, and PRL receptor. Furthermore, data showed activation of the Stat5 (signal transducer and activator of transcription 5) signaling pathway in the AROM+ male mammary gland. Interestingly, the phenotype observed is in part reversible. Treatment with finrozole, a specific aromatase inhibitor, caused an involution of the differentiated phenotype of the mammary gland, marked by the disappearance of alveolar structures and the majority of the tertiary side branches of the ducts. The present animal model is a valuable tool for better understanding the cellular and molecular mechanisms involved in the development of gynecomastia.

  8. Effects of putrescine, cadaverine, spermine, spermidine and beta-phenylethylamine on cultured bovine mammary epithelial cells

    DEFF Research Database (Denmark)

    Fusi, Eleonora; Baldi, Antonella; Cheli, Federica

    2008-01-01

    A bovine mammary epithelial cell line (BME-UV1) and three-dimensional collagen primary bovine organoids were used to evaluate the effects of cadaverine, putrescine, spermine, spermicline and beta-phenylethylamine on mammary epithelial cells. Each biogenic amine was diluted in several concentratio...

  9. Quantitative Assessment of Mammary Gland Density in Rodents Using Digital Image Analysis

    Directory of Open Access Journals (Sweden)

    Thompson Henry J

    2011-06-01

    Full Text Available Abstract Background Rodent models have been used extensively to study mammary gland development and for studies of toxicology and carcinogenesis. Mammary gland gross morphology can visualized via the excision of intact mammary gland chains following fixation and staining with carmine using a tissue preparation referred to as a whole mount. Methods are described for the automated collection of digital images from an entire mammary gland whole mount and for the interrogation of digital data using a "masking" technique available with Image-Pro® plus image analysis software (Mediacybernetics. Silver Spring, MD. Results Parallel to mammographic analysis in humans, measurements of rodent mammary gland density were derived from area-based or volume-based algorithms and included: total circumscribed mammary fat pad mass, mammary epithelial mass, and epithelium-free fat pad mass. These values permitted estimation of absolute mass of mammary epithelium as well as breast density. The biological plausibility of these measurements was evaluated in mammary whole mounts from rats and mice. During mammary gland development, absolute epithelial mass increased linearly without significant changes in mammographic density. Treatment of rodents with tamoxifen, 9-cis-retinoic acid, or ovariectomy, and occurrence of diet induced obesity decreased both absolute epithelial mass and mammographic density. The area and volumetric methods gave similar results. Conclusions Digital image analysis can be used for screening agents for potential impact on reproductive toxicity or carcinogenesis as well as for mechanistic studies, particularly for cumulative effects on mammary epithelial mass as well as translational studies of mechanisms that explain the relationship between epithelial mass and cancer risk.

  10. SHARPIN regulates collagen architecture and ductal outgrowth in the developing mouse mammary gland.

    Science.gov (United States)

    Peuhu, Emilia; Kaukonen, Riina; Lerche, Martina; Saari, Markku; Guzmán, Camilo; Rantakari, Pia; De Franceschi, Nicola; Wärri, Anni; Georgiadou, Maria; Jacquemet, Guillaume; Mattila, Elina; Virtakoivu, Reetta; Liu, Yuming; Attieh, Youmna; Silva, Kathleen A; Betz, Timo; Sundberg, John P; Salmi, Marko; Deugnier, Marie-Ange; Eliceiri, Kevin W; Ivaska, Johanna

    2017-01-17

    SHARPIN is a widely expressed multifunctional protein implicated in cancer, inflammation, linear ubiquitination and integrin activity inhibition; however, its contribution to epithelial homeostasis remains poorly understood. Here, we examined the role of SHARPIN in mammary gland development, a process strongly regulated by epithelial-stromal interactions. Mice lacking SHARPIN expression in all cells (Sharpin cpdm ), and mice with a stromal (S100a4-Cre) deletion of Sharpin, have reduced mammary ductal outgrowth during puberty. In contrast, Sharpin cpdm mammary epithelial cells transplanted in vivo into wild-type stroma, fully repopulate the mammary gland fat pad, undergo unperturbed ductal outgrowth and terminal differentiation. Thus, SHARPIN is required in mammary gland stroma during development. Accordingly, stroma adjacent to invading mammary ducts of Sharpin cpdm mice displayed reduced collagen arrangement and extracellular matrix (ECM) stiffness. Moreover, Sharpin cpdm mammary gland stromal fibroblasts demonstrated defects in collagen fibre assembly, collagen contraction and degradation in vitro Together, these data imply that SHARPIN regulates the normal invasive mammary gland branching morphogenesis in an epithelial cell extrinsic manner by controlling the organisation of the stromal ECM. © 2016 The Authors.

  11. ER and PR signaling nodes during mammary gland development.

    Science.gov (United States)

    Tanos, Tamara; Rojo, Lucia; Echeverria, Pablo; Brisken, Cathrin

    2012-07-19

    The ovarian hormones estrogen and progesterone orchestrate postnatal mammary gland development and are implicated in breast cancer. Most of our understanding of the molecular mechanisms of estrogen receptor (ER) and progesterone receptor (PR) signaling stems from in vitro studies with hormone receptor-positive cell lines. They have shown that ER and PR regulate gene transcription either by binding to DNA response elements directly or via other transcription factors and recruiting co-regulators. In addition they cross-talk with other signaling pathways through nongenomic mechanisms. Mouse genetics combined with tissue recombination techniques have provided insights about the action of these two hormones in vivo. It has emerged that hormones act on a subset of mammary epithelial cells and relegate biological functions to paracrine factors. With regards to hormonal signaling in breast carcinomas, global gene expression analyses have led to the identification of gene expression signatures that are characteristic of ERα-positive tumors that have stipulated functional studies of hitherto poorly understood transcription factors. Here, we highlight what has been learned about ER and PR signaling nodes in these different systems and attempt to lay out in which way the insights may converge.

  12. PHYLLOID TUMORS OF MAMMARY GLANDS. CURRENT STATE OF THE PROBLEM

    Directory of Open Access Journals (Sweden)

    A. D. Zikiryakhodzhaev

    2017-01-01

    Full Text Available Phylloid (leaf-shaped breast tumors are a rare disease and constitute 0.3–0.5% of all breast tumors. Due to the rare frequency of occurrence, as well as the small number of randomized studies that have been conducted on this pathology, there is currently no standardized approach to the diagnosis and treatment of phylloid tumors. The reports about these rare cases appearing in the literature are, as a rule, descriptive, which only emphasizes the difficulty of differential diagnosis, the development of the correct tactics for treating such patients. In connection with the rarity, it is very difficult to diagnose correctly this pathology, which requires a highly qualified doctor as a diagnostician in the initial contact with such a patient, and a pathologist doctor who establishes the final morphological diagnosis. Often, leaf-shaped tumors are mistaken for mammary fibroadenomas. Such difficulties in correct diagnosis in the preoperative period can lead to errors in the planning of treatment. Also, the recommendations for the treatment of patients with this diagnosis are not fully understood, since up to now there are no accepted treatment standards in both Russian and foreign recommendations. Due to the fact that this pathology of mammary glands is rare, the principles of treatment are based on small retrospective studies and clinical observations. In this review, we will discuss the results of major retrospective studies, including data on epidemiology, etiology, diagnostic approach, strategies and results of treatment of this complex group of breast pathologies.

  13. Assessment of mammary gland metabolism in the sow. II. Cellular metabolites in the mammary secretion and plasma during lactogenesis II.

    Science.gov (United States)

    Atwood, C S; Toussaint, J K; Hartmann, P E

    1995-05-01

    The concentrations of lactose, glucose, glucose 6-phosphate, glucose 1-phosphate, UDPglucose, UDPgalactose, UDP, UMP, inorganic phosphate, ADP and AMP (metabolites involved in the lactose synthesis pathway), and cAMP, galactose and fructose were measured in the mammary secretion from sucked (n = 9) and unsucked (n = 4) mammary glands of nine sows during the first 5 d post partum. The concentrations of lactose, glucose, galactose and fructose were also measured in plasma during this time. The progressive increase in the concentration of lactose, and changes in the concentrations of cellular metabolites in the mammary secretion from sucked glands were consistent with an increase in the metabolic activity of those glands during lactogenesis II. In contrast, unsucked glands showed a progressive decrease in the concentration of lactose, while the concentrations of cellular metabolites in the milk generally remained unchanged. These results indicated that there was no increase in the metabolic activity of unsucked glands (no increase in lactose synthesis or utilization of glucose and ATP) and that the rate of lactose synthesis prior to milk removal was limited by the availability of glucose and/or UDPgalactose. Therefore, the removal of colostrum from the mammary gland was necessary for an increase in the rate of lactose synthesis (and probably de novo fatty acid synthesis) and implies that autocrine mechanisms are operating to control the rate of milk synthesis during lactogenesis in the sow. The low concentration of glucose in colostrum compared with that in plasma is discussed in view of the paracellular pathway.

  14. Proteome analysis of functionally differentiated bovine (Bos indicus) mammary epithelial cells isolated from milk

    KAUST Repository

    Janjanam, Jagadeesh

    2013-10-01

    Mammary gland is made up of a branching network of ducts that end in alveoli. Terminally differentiated mammary epithelial cells (MECs) constitute the innermost layer of aveoli. They are milk-secreting cuboidal cells that secrete milk proteins during lactation. Little is known about the expression profile of proteins in the metabolically active MECs during lactation or their functional role in the lactation process. In the present investigation, we have reported the proteome map of MECs in lactating cows using 2DE MALDI-TOF/TOF MS and 1D-Gel-LC-MS/MS. MECs were isolated from milk using immunomagnetic beads and confirmed by RT-PCR and Western blotting. The 1D-Gel-LC-MS/MS and 2DE-MS/MS based approaches led to identification of 431 and 134 proteins, respectively, with a total of 497 unique proteins. Proteins identified in this study were clustered into functional groups using bioinformatics tools. Pathway analysis of the identified proteins revealed 28 pathways (p < 0.05) providing evidence for involvement of various proteins in lactation function. This study further provides experimental evidence for the presence of many proteins that have been predicted in annotated bovine genome. The data generated further provide a set of bovine MEC-specific proteins that will help the researchers to understand the molecular events taking place during lactation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Relationships between piglet growth rate and mammary gland size of the sow

    DEFF Research Database (Denmark)

    Nielsen, O.L.; Pedersen, Asger Roer; Sørensen, Martin Tang

    2001-01-01

    An experiment was conducted to study whether piglet growth rate is related to mammary gland size. It involved three primiparous sows and four multiparous sows that were fed ad libitum during the lactation period. The piglets received no creep feed. The weight and teat order of the piglets were......, intermediate in the middle and lowest in the rear glands. Average daily gain of the piglets was of the same magnitude regardless of gland position in the primiparous sows. In the multiparous sows, the piglets suckling the front teats had the highest gain while those suckling the middle teats had intermediate...... gain and those suckling the rear teats had the lowest gain. Average daily gain of the piglets in the lactation period was positively correlated to the amount of mammary tissue (0.35), mammary DNA (0.41) and mammary RNA (0.31), while correlations to mammary RNA concentration (0.28) and RNA/DNA ratio (0...

  16. Comparison between stearoyl-CoA desaturase expression in milk somatic cells and in mammary tissue of lactating dairy cows

    NARCIS (Netherlands)

    Jacobs, A.A.A.; Dijkstra, J.; Hendriks, W.H.; Baal, van J.; Vuuren, van A.M.

    2013-01-01

    Stearoyl-CoA desaturase (SCD) is an important enzyme in the bovine mammary gland, where it inserts a cis-double bond at the ¿9 position in a wide range of fatty acids. Investigating SCD expression in the bovine mammary gland generally requires invasive biopsy to obtain mammary tissue. The aim of

  17. Loss of Igfbp7 Causes Precocious Involution in Lactating Mouse Mammary Gland

    Science.gov (United States)

    Chatterjee, Sumanta; Bacopulos, Stephanie; Yang, Wenyi; Amemiya, Yutaka; Spyropoulos, Demetri

    2014-01-01

    Background Insulin like growth factors (IGFs) and their binding proteins (IGFBPs) are secreted peptides that play major roles in regulating the normal development and maturation of mammary gland. While Igfbp7 has been shown to decrease breast tumor growth, its role in regulating the normal mammary gland development has not been studied. To this end, we generated Igfbp7-null mice and examined the development and maturation of mammary glands in the virgin, pregnant and lactating animals. Results We report here that loss of Igfbp7 significantly retards mammary gland development in the virgin animals. More significantly, the pregnant Igfpb7-null glands contained fewer alveolar structures and that during lactation these glands exhibit the morphological changes that are associated with involution. The transcriptome profile of the Igfbp7-null glands on the lactation day 3 revealed a distinct involution-related gene signature compared to the lactating WT glands. Interestingly, we found that the lactating Igfbp7-null glands exhibit increased expression of Stat3 and enhanced activation of (phosphorylated) Stat3, combined with decreased expression of Stat5 suggesting that the absence of Igfbp7 accelerates the onset of involution. We also found that in absence of Igfpb7, the lactating glands contain increased Igfbp5 protein along with decreased expression of IGF-1 Receptor and Akt activation. Finally, we show that during the normal course of involution, Igfbp7 expression is significantly decreased in the mammary gland. Conclusion Our data suggest that loss of Igfbp7 induces precocious involution possibly through diminished cell survival signals. Our findings identify Igfbp7 as major regulator of involution in the mammary gland. PMID:24505323

  18. Alteration of gene expression in mammary gland tissue of dairy cows in response to dietary unsaturated fatty acids.

    Science.gov (United States)

    Mach, N; Jacobs, A A A; Kruijt, L; van Baal, J; Smits, M A

    2011-06-01

    The aim of this study was to determine the effects of supplementing unprotected dietary unsaturated fatty acids (UFAs) from different plant oils on gene expression in the mammary gland of grazing dairy cows. A total of 28 Holstein-Friesian dairy cows in mid-lactation were blocked according to parity, days in milk, milk yield and fat percentage. The cows were then randomly assigned to four UFA sources based on rapeseed, soybean, linseed or a mixture of the three oils for 23 days, after which, all 28 cows were switched to a control diet for an additional 28 days. On the last day of both periods, mammary gland biopsies were taken to study genome-wide differences in gene expression on Affymetrix GeneChip® Bovine Genome Arrays (no. 900493) by ServiceXS (Leiden, The Netherlands). Supplementation with UFAs resulted in increased milk yield but decreased milk fat and protein percentages. Furthermore, the proportion of de novo fatty acids (FAs) in the milk was reduced, whereas that of long-chain FAs increased. Applying a statistical cut-off of false discovery rate of q-values change of 1.3, a total of 972 genes were found to be significantly affected through UFA supplementation, indicating that large transcriptional adaptations occurred in the mammary gland when grazing dairy cows were supplemented with unprotected dietary UFA. Gene sets related to cell development and remodeling, apoptosis, nutrient metabolic process, as well as immune system response were predominantly downregulated during UFA supplementation. Such molecular knowledge on the physiology of the mammary gland might provide the basis for further functional research on dairy cows.

  19. Lactococcus lactis V7 inhibits the cell invasion of bovine mammary epithelial cells by Escherichia coli and Staphylococcus aureus.

    Science.gov (United States)

    Assis, B Seridan; Germon, P; Silva, A M; Even, S; Nicoli, J R; Le Loir, Y

    2015-01-01

    Bovine mastitis, an inflammatory disease of the mammary gland often associated to bacterial infection, is the first cause of antibiotic use in dairy cattle. Because of the risk of antibioresistance emergence, alternative non-antibiotic strategies are needed to prevent or to cure bovine mastitis and reduce the antibiotic use in veterinary medicine. In this work, we investigated Lactococcus lactis V7, a strain isolated from the mammary gland, as a probiotic option against bovine mastitis. Using bovine mammary epithelial cell (bMEC) culture, and two representative strains for Escherichia coli and for Staphylococcus aureus, two major mastitis pathogens, we investigated L. lactis V7 ability to inhibit cell invasion (i.e. adhesion and internalization) of these pathogens into bMEC. L. lactis V7 ability to modulate the production of CXCL8, a key chemokine IL-8 responsible for neutrophil influx, in bMEC upon challenge with E. coli was investigated by an ELISA dosage of CXCL8 in bMEC culture supernatants. We showed that L. lactis V7 inhibited the internalisation of both E. coli and S. aureus strains into bMEC, whereas it inhibited the adhesion of only one out of the two S. aureus strains and of none of the E. coli strains tested. Investigation of the bMEC immune response showed that L. lactis V7 alone induced a slight increase in CXCL8 production in bMEC and that it increased the inflammatory response in bMEC challenged with the E. coli strains. Altogether these features of L. lactis V7 make it a potential promising candidate for a probiotic prevention strategy against bovine mastitis.

  20. Unlocking the milk protein gene loci during mammary gland development and differentiation; a role for chromatin

    Science.gov (United States)

    Mammary gland development and differentiation occur mostly postnatally. Chromatin organization plays a key role in transcriptional and epigenetic regulation during development and differentiation. Considerable knowledge of the systemic hormones and local growth factors important for development and ...

  1. ATM is required for SOD2 expression and homeostasis within the mammary gland.

    Science.gov (United States)

    Dyer, Lisa M; Kepple, Jessica D; Ai, Lingbao; Kim, Wan-Ju; Stanton, Virginia L; Reinhard, Mary K; Backman, Lindsey R F; Streitfeld, W Scott; Babu, Nivetha Ramesh; Treiber, Nicolai; Scharffetter-Kochanek, Karin; McKinnon, Peter J; Brown, Kevin D

    2017-12-01

    ATM activates the NF-κB transcriptional complex in response to genotoxic and oxidative stress. The purpose of this study was to examine if the NF-κB target gene and critical antioxidant SOD2 (MnSOD) in cultured mammary epithelium is also ATM-dependent, and what phenotypes arise from deletion of ATM and SOD2 within the mammary gland. SOD2 expression was studied in human mammary epithelial cells and MCF10A using RNAi to knockdown ATM or the NF-κB subunit RelA. To study ATM and SOD2 function in mammary glands, mouse lines containing Atm or Sod2 genes containing LoxP sites were mated with mice harboring Cre recombinase under the control of the whey acidic protein promoter. Quantitative PCR was used to measure gene expression, and mammary gland structure was studied using histology. SOD2 expression is ATM- and RelA-dependent, ATM knockdown renders cells sensitive to pro-oxidant exposure, and SOD mimetics partially rescue this sensitivity. Mice with germline deletion of Atm fail to develop mature mammary glands, but using a conditional knockout approach, we determined that Atm deletion significantly diminished the expression of Sod2. We also observed that these mice (termed AtmΔ/Δ) displayed a progressive lactation defect as judged by reduced pup growth rate, aberrant lobulo-alveolar structure, diminished milk protein gene expression, and increased apoptosis within lactating glands. This phenotype appears to be linked to dysregulated Sod2 expression as mammary gland-specific deletion of Sod2 phenocopies defects observed in AtmΔ/Δ dams. We conclude that ATM is required to promote expression of SOD2 within the mammary epithelium, and that both ATM and SOD2 play a crucial role in mammary gland homeostasis.

  2. Repertoire of Escherichia coli agonists sensed by innate immunity receptors of the bovine udder and mammary epithelial cells

    Directory of Open Access Journals (Sweden)

    Porcherie Adeline

    2012-02-01

    Full Text Available Abstract Escherichia coli is a frequent cause of clinical mastitis in dairy cows. It has been shown that a prompt response of the mammary gland after E. coli entry into the lumen of the gland is required to control the infection, which means that the early detection of bacteria is of prime importance. Yet, apart from lipopolysaccharide (LPS, little is known of the bacterial components which are detected by the mammary innate immune system. We investigated the repertoire of potential bacterial agonists sensed by the udder and bovine mammary epithelial cells (bMEC during E. coli mastitis by using purified or synthetic molecular surrogates of bacterial agonists of identified pattern-recognition receptors (PRRs. The production of CXCL8 and the influx of leucocytes in milk were the readouts of reactivity of stimulated cultured bMEC and challenged udders, respectively. Quantitative PCR revealed that bMEC in culture expressed the nucleotide oligomerization domain receptors NOD1 and NOD2, along with the Toll-like receptors TLR1, TLR2, TLR4, and TLR6, but hardly TLR5. In line with expression data, bMEC proved to react to the cognate agonists C12-iE-DAP (NOD1, Pam3CSK4 (TLR1/2, Pam2CSK4 (TLR2/6, pure LPS (TLR4, but not to flagellin (TLR5. As the udder reactivity to NOD1 and TLR5 agonists has never been reported, we tested whether the mammary gland reacted to intramammary infusion of C12-iE-DAP or flagellin. The udder reacted to C12-iE-DAP, but not to flagellin, in line with the reactivity of bMEC. These results extend our knowledge of the reactivity of the bovine mammary gland to bacterial agonists of the innate immune system, and suggest that E. coli can be recognized by several PRRs including NOD1, but unexpectedly not by TLR5. The way the mammary gland senses E. coli is likely to shape the innate immune response and finally the outcome of E. coli mastitis.

  3. Stem/progenitor cells in non-lactating versus lactating equine mammary gland

    OpenAIRE

    Spaas, Jan; Chiers, Koen; Bussche, Leen; Burvenich, Christian; Van de Walle, Gerlinde

    2012-01-01

    The mammary gland is a highly regenerative organ that can undergo multiple cycles of proliferation, lactation, and involution. Based on the facts that (i) mammary stem/progenitor cells (MaSC) are proposed to be the driving forces behind mammary growth and function and (ii) variation exists between mammalian species with regard to physiological and pathological functioning of this organ, we believe that studying MaSC from different mammals is of great comparative interest. Over the years, impo...

  4. Regulation of Mammary Gland Sensitivity to Thyroid Hormones during the Transition from Pregnancy to Lactation

    Science.gov (United States)

    Thyroid hormones are galactopoietic and appear to assist in establishing the mammary gland’s metabolic priority during lactation. Expression patterns for genes that can alter tissue sensitivity to thyroid hormones and thyroid hormone activity were evaluated in the mammary gland and liver of Holstei...

  5. Mammary gland leptin in relation to lactogenesis in the periparturient dairy goat

    DEFF Research Database (Denmark)

    Rasmussen, Alice Neess; Nielsen, Mette Olaf; Tauson, Anne-Helene

    2008-01-01

    The role of leptin in development of mammary gland secretory function was studied during the periparturient period in dairy goats. Changes in mammary leptin and leptin receptor (short cytoplasmic form) expression were evaluated by real-time RT-PCR and related to changes in milk and plasma leptin ...

  6. The assessment of the prevalence of associated benign pathology of thyroid and mammary glands

    OpenAIRE

    VASIUKHINA I.A.; DANILOVA L.I.

    2012-01-01

    Objective: to assess the prevalence of associated benign pathology of thyroid and mammary glands in women with unsuppressed menstrual cycle. Materials and methods: 265 women with unsuppressed menstrual cycle (MC) were examined by the sample method. The examination of the women included ultrasonography of thyroid and mammary glands with the detector-frequency of 7.5 MHz. The thyroid status and clinicolaboratory indicators of the reproductive system were estimated. Results. The prevalence of th...

  7. Redirection of Human Cancer Cells upon the Interaction with the Regenerating Mouse Mammary Gland Microenvironment

    Directory of Open Access Journals (Sweden)

    Sonia M. Rosenfield

    2013-01-01

    Full Text Available Tumorigenesis is often described as a result of accumulated mutations that lead to growth advantage and clonal expansion of mutated cells. There is evidence in the literature that cancer cells are influenced by the microenvironment. Our previous studies demonstrated that the mouse mammary gland is capable of redirecting mouse cells of non-mammary origins as well as Mouse Mammary Tumor Virus (MMTV-neu transformed cells toward normal mammary epithelial cell fate during gland regeneration. Interestingly, the malignant phenotype of MMTV-neu transformed cells was suppressed during serial transplantation experiments. Here, we discuss our studies that demonstrated the potential of the regenerating mouse mammary gland to redirect cancer cells of different species into a functional tumor-free mammary epithelial cell progeny. Immunochemistry for human specific CD133, mitochondria, cytokeratins as well as milk proteins and FISH for human specific probe identified human epithelial cell progeny in ducts, lobules, and secretory acini. Fluorescent In Situ Hybridization (FISH for human centromeric DNA and FACS analysis of propidium iodine staining excluded the possibility of mouse-human cell fusion. To our knowledge this is the first evidence that human cancer cells of embryonic or somatic origins respond to developmental signals generated by the mouse mammary gland microenvironment during gland regeneration in vivo.

  8. Milk composition and health status from mammary gland quarters adjacent to glands affected with naturally occurring clinical mastitis.

    Science.gov (United States)

    Paixão, Marcel G; Abreu, Luiz R; Richert, Roxann; Ruegg, Pamela L

    2017-09-01

    Mammary gland quarters have usually been considered to be anatomically and physiologically independent, but some recent research has indicated more interdependence than previously reported. The objective of this study was to compare milk composition (fat, total protein, lactose, solids-not-fat, and chloride) and health status (somatic cell count, differential leukocyte count, and lactate dehydrogenase) of milk samples from unaffected mammary glands of an udder with a single clinically inflamed quarter to results of milk samples from healthy mammary glands of healthy cows. The study was designed as a prospective case control study with case and control cows matched by parity and days in milk. Cases were defined as cows (n = 59) experiencing clinical mastitis in a single mammary gland, and controls (n = 59) were defined as cows that had not experienced clinical mastitis during the current lactation. Quarter milk samples were collected from all mammary glands adjacent to clinically affected quarters of cases and from the same mammary glands of controls. Samples were used to assess concentration of chloride and lactate dehydrogenase, fat, total protein, solids-not-fat, somatic cell count, and differential leukocyte count. Microbiological analysis was also performed on milk samples obtained from clinically affected mammary glands (n = 59). Logistic regression models were used to assess possible associations among quarter somatic cell count (≥150,000 cells/mL) and quarter type (adjacent to case or control). Multivariate linear models were used to compare milk composition and health status between quarter types. A total of 170 quarters were enrolled per group. Milk obtained from adjacent quarters of cases contained a lesser concentration of total protein, lactose, and solids-not-fat, but had a greater concentration of fat and chloride. The somatic cell count, total leukocyte count, and absolute numbers of neutrophils, lymphocytes, and macrophages were all increased in

  9. Anal Papilloma: An Exceptional Presentation of Fibrocystic Disease in Anogenital Mammary-Like Glands.

    Science.gov (United States)

    Subashchandrabose, Priya; Esakkai, Muthuvel; Venugopal, Palani; Kannaiyan, Ilavarasan; Srinivasan, Chitra; Reddy, Punuru Tejashwini; Ebenezer, Evelyn Elizabeth

    2015-01-01

    Previously ectopic breast tissue was thought to be derived from the caudal remnants of the primitive embryonic milk ridges; anogenital mammary-like glands are presently considered as normal constituents of the anogenital region. We report a case of young female, who presented with an anal papilloma. Histopathological examination revealed extensive fibrocystic changes in anogenital mammary-like glands. To date, a lot of benign changes and a wide range of benign and malignant neoplasms have been reported in these glands. However, extensive fibrocystic change of these glands in anal region is very rare. In addition, fibrocystic disease of anal mammary glands, masquerading clinically as an anal papilloma, has not been reported in literature. Hence, it is essential for clinicians and the pathologists to be aware of such a rare presentation. The features of fibrocystic disease in perianal region are also discussed.

  10. Anal Papilloma: An Exceptional Presentation of Fibrocystic Disease in Anogenital Mammary-Like Glands

    Directory of Open Access Journals (Sweden)

    Priya Subashchandrabose

    2015-01-01

    Full Text Available Previously ectopic breast tissue was thought to be derived from the caudal remnants of the primitive embryonic milk ridges; anogenital mammary-like glands are presently considered as normal constituents of the anogenital region. We report a case of young female, who presented with an anal papilloma. Histopathological examination revealed extensive fibrocystic changes in anogenital mammary-like glands. To date, a lot of benign changes and a wide range of benign and malignant neoplasms have been reported in these glands. However, extensive fibrocystic change of these glands in anal region is very rare. In addition, fibrocystic disease of anal mammary glands, masquerading clinically as an anal papilloma, has not been reported in literature. Hence, it is essential for clinicians and the pathologists to be aware of such a rare presentation. The features of fibrocystic disease in perianal region are also discussed.

  11. Diet-induced obesity impairs mammary development and lactogenesis in murine mammary gland.

    Science.gov (United States)

    Flint, David J; Travers, Maureen T; Barber, Michael C; Binart, Nadine; Kelly, Paul A

    2005-06-01

    We have developed a mouse model of diet-induced obesity that shows numerous abnormalities relating to mammary gland function. Animals ate approximately 40% more calories when offered a high-fat diet and gained weight at three times the rate of controls. They exhibited reduced conception rates, increased peripartum pup mortality, and impaired lactogenesis. The impairment of lactogenesis involved lipid accumulation in the secretory epithelial cells indicative of an absence of copius milk secretion. Expression of mRNAs for beta-casein, whey acid protein, and alpha-lactalbumin were all decreased immediately postpartum but recovered as lactation was established over 2-3 days. Expression of acetyl-CoA carboxylase (ACC)-alpha mRNA was also decreased at parturition as was the total enzyme activity, although there was a compensatory increase in the proportion in the active state. By day 10 of lactation, the proportion of ACC in the active state was also decreased in obese animals, indicative of suppression of de novo fatty acid synthesis resulting from the supply of preformed fatty acids in the diet. Although obese animals consumed more calories in the nonpregnant and early pregnant states, they showed a marked depression in fat intake around day 9 of pregnancy before food intake recovered in later pregnancy. Food intake increased dramatically in both lean and obese animals during lactation although total calories consumed were identical in both groups. Thus, despite access to high-energy diets, the obese animals mobilized even more adipose tissue during lactation than their lean counterparts. Obese animals also exhibited marked abnormalities in alveolar development of the mammary gland, which may partially explain the delay in differentiation evident during lactogenesis.

  12. Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development.

    Science.gov (United States)

    Tan, J; Buache, E; Alpy, F; Daguenet, E; Tomasetto, C-L; Ren, G-S; Rio, M-C

    2014-07-31

    MMP-11 is a bad prognosis paracrine factor in invasive breast cancers. However, its mammary physiological function remains largely unknown. In the present study we have investigated MMP-11 function during postnatal mammary gland development and function using MMP-11-deficient (MMP-11-/-) mice. Histological and immunohistochemical analyses as well as whole-mount mammary gland staining show alteration of the mammary gland in the absence of MMP-11, where ductal tree, alveolar structures and milk production are reduced. Moreover, a series of transplantation experiments allowed us to demonstrate that MMP-11 exerts an essential local paracrine function that favors mammary gland branching and epithelial cell outgrowth and invasion through adjacent connective tissues. Indeed, MMP-11-/- cleared fat pads are not permissive for wild-type epithelium development, whereas MMP-11-/- epithelium transplants grow normally when implanted in wild-type cleared fat pads. In addition, using primary mammary epithelial organoids, we show in vitro that this MMP-11 pro-branching effect is not direct, suggesting that MMP-11 acts via production/release of stroma-associated soluble factor(s). Finally, the lack of MMP-11 leads to decreased periductal collagen content, suggesting that MMP-11 has a role in collagen homeostasis. Thus, local stromal MMP-11 might also regulate mammary epithelial cell behavior mechanically by promoting extracellular matrix stiffness. Collectively, the present data indicate that MMP-11 is a paracrine factor involved during postnatal mammary gland morphogenesis, and support the concept that the stroma strongly impact epithelial cell behavior. Interestingly, stromal MMP-11 has previously been reported to favor malignant epithelial cell survival and promote cancer aggressiveness. Thus, MMP-11 has a paracrine function during mammary gland development that might be harnessed to promote tumor progression, exposing a new link between development and malignancy.

  13. Characterisation of microRNA expression in post-natal mouse mammary gland development

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    Karagavriilidou Konstantina

    2009-11-01

    Full Text Available Abstract Background The differential expression pattern of microRNAs (miRNAs during mammary gland development might provide insights into their role in regulating the homeostasis of the mammary epithelium. Our aim was to analyse these regulatory functions by deriving a comprehensive tissue-specific combined miRNA and mRNA expression profile of post-natal mouse mammary gland development. We measured the expression of 318 individual murine miRNAs by bead-based flow-cytometric profiling of whole mouse mammary glands throughout a 16-point developmental time course, including juvenile, puberty, mature virgin, gestation, lactation, and involution stages. In parallel whole-genome mRNA expression data were obtained. Results One third (n = 102 of all murine miRNAs analysed were detected during mammary gland development. MicroRNAs were represented in seven temporally co-expressed clusters, which were enriched for both miRNAs belonging to the same family and breast cancer-associated miRNAs. Global miRNA and mRNA expression was significantly reduced during lactation and the early stages of involution after weaning. For most detected miRNA families we did not observe systematic changes in the expression of predicted targets. For miRNA families whose targets did show changes, we observed inverse patterns of miRNA and target expression. The data sets are made publicly available and the combined expression profiles represent an important community resource for mammary gland biology research. Conclusion MicroRNAs were expressed in likely co-regulated clusters during mammary gland development. Breast cancer-associated miRNAs were significantly enriched in these clusters. The mechanism and functional consequences of this miRNA co-regulation provide new avenues for research into mammary gland biology and generate candidates for functional validation.

  14. Identification of stable and oestrus cycle-independent housekeeping genes in the rat mammary gland and other tissues

    DEFF Research Database (Denmark)

    Hvid, Henning; Ekstrøm, Claus T; Vienberg, Sara Gry

    2011-01-01

    The function and development of the rat mammary gland is dependent on the oestrus cycle. Normalization of gene expression in mammary gland samples assessed by quantitative RT-PCR therefore requires housekeeping genes (HKGs) which are stably expressed during the oestrus cycle. mRNA expression of 10...... HKGs was measured in the rat mammary gland at different phases of the oestrus cycle. In addition, mRNA expression of the HKGs was measured in a panel of other rat tissues comprising laser microdissected mammary gland alveolar lobules and interlobular connective tissue and macrodissected mammary gland......, liver, skeletal muscle, colon and ovary samples. Expression and ranking of HKGs varied between tissues and oestrus cycle phases and several HKGs were necessary for normalization between samples. In the mammary gland samples, three HKGs (Sdha, Tbp, and Atp5b) were identified as the optimal combination...

  15. Functional Analyse of GLUT1 and GLUT12 in Glucose Uptake in Goat Mammary Gland Epithelial Cells

    OpenAIRE

    Yu, Qinghua; Zhu, Liqi; Lin, Jian; Zhang, Qiang; Tian, Qi; Hu, Weiwei; Yang, Qian

    2013-01-01

    Glucose transport, mediated by glucose transporters, is necessary for mammary gland development and lactation. GLUT1 and GLUT12 could both be expressed in the pregnant and lactating mammary gland to participate in the glucose uptake process. In this study, the goat GLUT1 and GLUT12 genes were cloned from Saanen dairy goats and transfected into goat mammary gland epithelial cells to assess their biological functions and distributions. The results showed that both goat GLUT1 and GLUT12 had 12 p...

  16. Phyllodes Tumor of Anogenital Mammary-like Glands with Diffuse Pseudoangiomatous Stromal Hyperplasia

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    Nuket ELİYATKIN

    2017-05-01

    Full Text Available Anogenital mammary-like glands may give rise to various pathologic lesions identical to those known in mammary pathology. Tumor occurring in the anogenital region is extremely rare. The histogenetic origin of this tumor is controversial as it is being debated whether such lesions evolve from ectopic breast tissue and most recently, anogenital mammary-like gland. We report a 28-year-old girl who presented with a painless mass in the anogenital region, which was subsequently excised. Microscopic examination revealed morphologic pattern characteristic of benign phyllodes tumor with pseudoangiomatous stromal hyperplasia. We present this case to emphasize the importance of recognizing this uncommon lesion occurring at an extremely unusual site. We also discuss the histogenesis of phyllodes tumor and related lesions occurring in the anogenital region in light of the current literature along with a brief review of the previously reported cases of anogenital mammary-like glands.

  17. Unique expression pattern of the three insulin receptor family members in the rat mammary gland

    DEFF Research Database (Denmark)

    Hvid, Henning; Klopfleisch, Robert; Vienberg, Sara Gry

    2011-01-01

    Supra-pharmacological doses of the insulin analog X10 (AspB10) increased the incidence of mammary tumors in female Sprague-Dawley rats in chronic toxicity studies, most likely via receptor-mediated mechanisms. However, little is known about the expression of the insulin receptor family in the rat...... mammary gland. Using laser micro-dissection, quantitative RT-PCR and immunohistochemistry, we examined the expression of IR (insulin receptor), IGF-1R (IGF-1 receptor), IRR (insulin receptor-related receptor), ERα (estrogen receptor alpha), ERβ (estrogen receptor beta) and PR (progesteron receptor......) in young, virgin, female Sprague-Dawley rats and compared to expression in reference organs. The mammary gland displayed the highest expression of IRR and IGF-1R. In contrast, low expression of IR transcripts was observed in the mammary gland tissue with expression of the IR-A isoform being 5-fold higher...

  18. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands.

    Science.gov (United States)

    Chiosea, Simion I; Griffith, Christopher; Assaad, Adel; Seethala, Raja R

    2012-09-01

    Mammary analogue secretory carcinoma (MASC) is a recently described tumour with ETV6 translocation. We aimed to characterize the clinical significance of recognizing MASC. Thirty-six patients with MASC (27 identified retrospectively and nine prospectively) are presented. Historically, MASC mimicked other salivary tumours, as follows: 14 of 37 (37.8%) adenocarcinoma, not otherwise specified, 11 of 89 (12.4%) acinic cell carcinomas (AciCC), one of five (20%) mucin-producing signet ring adenocarcinomas, and one of 165 (0.6%) mucoepidermoid carcinomas. Demographically, MASC affected males more commonly (1.4:1). The average age at diagnosis was 45.7 years. Parotid gland was the most common site of involvement (26 of 36, 72.2%), although other head and neck sites, including the base of tongue, were affected. Of 18 patients with neck dissection, lymph node involvement was identified in four patients (four of 18, 22.2%). Survival analysis of MASC cases presented here, combined with those reported previously, revealed a mean disease-free survival for patients with MASC of 92 months [n = 29; 95% confidence interval (CI) 71-115 months], compared with a mean DFS of 121 months for patients with AciCC (n = 38; 95% CI 92-149, P = 0.43). Although perhaps slightly more aggressive, MASC clinical outcome mimics that of AciCC. © 2012 Blackwell Publishing Ltd.

  19. Large lipid-rich mammary analogue secretory carcinoma of parotid gland: An unusual case.

    Science.gov (United States)

    Joshi, Prashant; Mridha, Asit Ranjan; Singh, Shuchita; Kinra, Prateek; Ray, Ruma; Thakar, Alok

    2015-01-01

    Mammary analogue secretory carcinoma (MASC) of the salivary gland is a malignant tumor which bears morphologic, immunohistochemical and molecular features similar to those of mammary secretory carcinoma. The tumor is considered as a low-grade malignancy perhaps slightly more aggressive than acinic cell carcinoma. High-grade transformation with recurrences, regional nodal involvement, metastases, and cancer-related death has been reported in a few cases. We report an unusual case of large MASC of the parotid gland in a young patient without regional lymph node involvement. To the best of our knowledge till date such a large MASC of the salivary gland has not been reported in the English literature.

  20. Inhibition of peripubertal sheep mammary gland development by cysteamine through reducing progesterone and growth factor production.

    Science.gov (United States)

    Zhao, Yong; Feng, Yanni; Zhang, Hongfu; Kou, Xin; Li, Lan; Liu, Xinqi; Zhang, Pengfei; Cui, Liantao; Chu, Meiqiang; Shen, Wei; Min, Lingjiang

    2017-02-01

    Cysteamine has been used for treating cystinosis for many years, and furthermore it has also been used as a therapeutic agent for different diseases including Huntington's disease, Parkinson's disease (PD), nonalcoholic fatty liver disease, malaria, cancer, and others. Although cysteamine has many potential applications, its use may also be problematic. The effects of low doses of cysteamine on the reproductive system, especially the mammary glands are currently unknown. In the current investigation, low dose (10 mg/kg BW/day) of cysteamine did not affect sheep body weight gain or organ index of the liver, spleen, or heart; it did, however, increase the levels of blood lymphocytes, monocytes, and platelets. Most interestingly, it inhibited mammary gland development after 2 or 5 months of treatment by reducing the organ index and the number of mammary gland ducts. Plasma growth hormone and estradiol remained unchanged; however, plasma progesterone levels and the protein level of HSD3β1 in sheep ovaries were decreased by cysteamine. In addition to steroid hormones, growth factors produced in the mammary glands also play crucial roles in mammary gland development. Results showed that protein levels of HGF, GHR, and IGF1R were decreased after 5 months of cysteamine treatment. These findings together suggest that progesterone and local growth factors in mammary glands might be involved in cysteamine initiated inhibition of pubertal ovine mammary gland development. Furthermore, it may lead to a reduction in fertility. Therefore, cysteamine should be used with great caution until its actions have been further investigated and its limitations overcome. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Loss of Panx1 Impairs Mammary Gland Development at Lactation: Implications for Breast Tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Michael K G Stewart

    Full Text Available Pannexin1 (Panx1 subunits oligomerize to form large-pore channels between the intracellular and extracellular milieu that have been shown to regulate proliferation, differentiation and cell death mechanisms. These key cellular responses are ultimately necessary for normal tissue development and function but the role of Panx1 in development, differentiation and function in many tissues remains unexplored, including that of the breast. Panx1 was identified to be expressed in the mammary gland through western blot and immunofluorescent analysis and is dynamically upregulated during pregnancy and lactation. In order to evaluate the role of Panx1 in the context of mammary gland development and function, Panx1-/- mice were evaluated in comparison to wild-type mice in the mammary glands of virgin, lactating and involuting mice. Our results revealed that Panx1 ablation did not affect virgin or involuting mammary glands following histological and whole mount analysis. Panx1 was necessary for timely alveolar development during early lactation based on a decreased number of alveolar lumen following histological analysis and reduced proliferation following Ki67 immunofluorescent labelling. Importantly, the loss of Panx1 in lactating mammary glands did not overtly affect epithelial or secretory differentiation of the mammary gland suggesting that Panx1 is not critical in normal mammary gland function. In addition, PANX1 mRNA expression was correlated with negative clinical outcomes in patients with breast cancer using in silico arrays. Together, our results suggest that Panx1 is necessary for timely alveolar development following the transition from pregnancy to lactation, which may have implications extending to patients with breast cancer.

  2. First demonstration of decorin, an extracellular matrix molecule, in bovine mammary tissue

    Science.gov (United States)

    In the mammary gland, the extracellular matrix (ECM) is secreted by and surrounds cells located in both mammary parenchyma (PAR) and stroma. Decorin is an ECM proteoglycan with cell growth regulatory effects mediated by its ability to interact with growth factors or up-regulation of cyclin-dependent...

  3. Histopathology of mammary gland in Staphylococcus aureus induced mastitis in mice

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    Jayaraj Fakkirappa Chinchali

    2014-02-01

    Full Text Available Objective: To investigate the histopathological changes of mouse mammary tissue damage in dose and durational pathogenicity of Staphylococcus aureus (S. aureus inoculums. Methods: The minimal tissue inflammation dose of S. aureus inoculum was determined by inoculating the lactating mice mammary gland to observe the mortality rate at 24, 48, 72 and 96 h of infection for each inoculum dilutions. To study dose pathogenicity, lactating mice were divided into one control and four induced groups of 5 mice each. S. aureus inoculums doses of 0.8伊101, 1.4 伊102, 2伊102 and 2.8伊103 colony forming unit were inoculated to the induced groups II, III, IV and V respectively. Mice were sacrificed and mammary gland tissues were harvested after 48 h of infection. Similarly to study of durational pathogenicity, a dose of 2伊102 colony forming unit of S. aureus inoculums was inoculated to the induced groups II, III, IV and V respectively. Mice were sacrificed and mammary gland tissues were harvested after 24, 48, 72 and 96 h of infection. Body and mammary gland were weighed and histopathological responses of the tissue damage were observed for both dose and durational pathogenicity ’s of S. aureus inoculums. Results: The observations indicated mastitis symptoms, decrease in body and mammary gland weights. Histopathological evidences revealed massive infiltration of polymorphonuclear neutrophil leukocytes, damage of alveoli and secretory products as the doses and durations of S. aureus inoculum increased compared to the control. Conclusions: The present study revealed that damage in mammary gland tissue of mice increased as the dose and duration of S. aureus inoculums increased.

  4. Histologic and Immunohistochemical classification of 41 bovine adrenal gland neoplasms

    DEFF Research Database (Denmark)

    Grossi, Anette Blak; Leifsson, Páll S.; Jensen, Henrik Elvang

    2013-01-01

    Tumors of the adrenal glands are among the most frequent tumors in cattle; however, few studies have been conducted to describe their characteristics. The aim of this study was to classify 41 bovine adrenal neoplasms from 40 animals based on macroscopic and histologic examination, including...

  5. Salvia officinalis L. induces alveolar bud growing in adult female rat mammary glands.

    Science.gov (United States)

    Monsefi, Malihezaman; Abedian, Mehrnaz; Azarbahram, Zahra; Ashraf, Mohammad Javad

    2015-01-01

    In traditional medicine Salvia officinalis (sage) has been used as menstrual cycle regulator. In the present study the effects of sage extract on breast tissue were examined. Fourteen female rats were divided into two groups: 1) Distilled water-treated rats (Con) that were gavaged with 1ml distilled water and 2) Saliva officinalis hydroalcoholic extract (SHE)-treated rats that were gavaged with 30mg/kg/body weight of sage extract for 30 days. The estrus cycle changes were monitored by daily examination of vaginal smear. Whole mounts of right pelvic breast were spread on the slide and stained by carmine. The number of alveolar buds (ABs) type 1 and 2 and lobules of mammary gland were scored. Tissue sections of left pelvic mammary gland were prepared and its histomorphometrical changes were measured. Blood samples were taken from dorsal aorta and estradiol and progesterone concentrations were measured using radioimmunoassay. Estrous cycles decreased significantly in SHE-treated animals. The number of alveolar buds and lobules in mammary gland whole mount of SHE-treated group were higher than the Con group. The number and diameter of ducts in histological section of mammary gland in SHE-treated group increased as compared to the Con group. Sage promotes alveologenesis of mammary glands and it can be used as a lactiferous herb.

  6. Epigenetic modifications unlock the milk protein gene loci during mouse mammary gland development and differentiation.

    Directory of Open Access Journals (Sweden)

    Monique Rijnkels

    Full Text Available Unlike other tissues, development and differentiation of the mammary gland occur mostly after birth. The roles of systemic hormones and local growth factors important for this development and functional differentiation are well-studied. In other tissues, it has been shown that chromatin organization plays a key role in transcriptional regulation and underlies epigenetic regulation during development and differentiation. However, the role of chromatin organization in mammary gland development and differentiation is less well-defined. Here, we have studied the changes in chromatin organization at the milk protein gene loci (casein, whey acidic protein, and others in the mouse mammary gland before and after functional differentiation.Distal regulatory elements within the casein gene cluster and whey acidic protein gene region have an open chromatin organization after pubertal development, while proximal promoters only gain open-chromatin marks during pregnancy in conjunction with the major induction of their expression. In contrast, other milk protein genes, such as alpha-lactalbumin, already have an open chromatin organization in the mature virgin gland. Changes in chromatin organization in the casein gene cluster region that are present after puberty persisted after lactation has ceased, while the changes which occurred during pregnancy at the gene promoters were not maintained. In general, mammary gland expressed genes and their regulatory elements exhibit developmental stage- and tissue-specific chromatin organization.A progressive gain of epigenetic marks indicative of open/active chromatin on genes marking functional differentiation accompanies the development of the mammary gland. These results support a model in which a chromatin organization is established during pubertal development that is then poised to respond to the systemic hormonal signals of pregnancy and lactation to achieve the full functional capacity of the mammary gland.

  7. Functional development of the adult ovine mammary gland--insights from gene expression profiling.

    Science.gov (United States)

    Paten, Amy M; Duncan, Elizabeth J; Pain, Sarah J; Peterson, Sam W; Kenyon, Paul R; Blair, Hugh T; Dearden, Peter K

    2015-10-05

    The mammary gland is a dynamic organ that undergoes dramatic physiological adaptations during the transition from late pregnancy to lactation. Investigation of the molecular basis of mammary development and function will provide fundamental insights into tissue remodelling as well as a better understanding of milk production and mammary disease. This is important to livestock production systems and human health. Here we use RNA-seq to identify differences in gene expression in the ovine mammary gland between late pregnancy and lactation. Between late pregnancy (135 days of gestation ± 2.4 SD) and lactation (15 days post partum ± 1.27 SD) 13 % of genes in the sheep genome were differentially expressed in the ovine mammary gland. In late pregnancy, cell proliferation, beta-oxidation of fatty acids and translation were identified as key biological processes. During lactation, high levels of milk fat synthesis were mirrored by enrichment of genes associated with fatty acid biosynthesis, transport and lipogenesis. Protein processing in the endoplasmic reticulum was enriched during lactation, likely in support of active milk protein synthesis. Hormone and growth factor signalling and activation of signal transduction pathways, including the JAK-STAT and PPAR pathways, were also differently regulated, indicating key roles for these pathways in functional development of the ovine mammary gland. Changes in the expression of epigenetic regulators, particularly chromatin remodellers, indicate a possible role in coordinating the large-scale transcriptional changes that appear to be required to switch mammary processes from growth and development during late pregnancy to synthesis and secretion of milk during lactation. Coordinated transcriptional regulation of large numbers of genes is required to switch between mammary tissue establishment during late pregnancy, and activation and maintenance of milk production during lactation. Our findings indicate the remarkable

  8. Prototheca zopfii isolated from bovine mastitis induced oxidative stress and apoptosis in bovine mammary epithelial cells.

    Science.gov (United States)

    Shahid, Muhammad; Gao, Jian; Zhou, Yanan; Liu, Gang; Ali, Tariq; Deng, Youtian; Sabir, Naveed; Su, Jingliang; Han, Bo

    2017-05-09

    Bovine protothecal mastitis results in considerable economic losses worldwide. However, Prototheca zopfii induced morphological alterations and oxidative stress in bovine mammary epithelial cells (bMECs) is not comprehensively studied yet. Therefore, the aim of this current study was to investigate the P. zopfii induced pathomorphological changes, oxidative stress and apoptosis in bMECs. Oxidative stress was assessed by evaluating catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) contents and lactate dehydrogenase (LDH) activity, while ROS generation and apoptosis was measured by confocal laser scanning microscopy. The results revealed that infection of P. zopfii genotype II (GTII) significantly changed bMECs morphology, increased apoptotic rate and MDA contents at 12 h (p effects in bMECs, and the findings of this study concluded that GTII induced apoptosis and oxidative stress in bMECs via the imbalance of oxidant and antioxidant defenses as well as the production of intracellular ROS.

  9. [Clinicopathologic features of mammary analogue secretory carcinoma of salivary glands].

    Science.gov (United States)

    Zhang, X P; Ni, H; Wang, X; Chen, H; Shi, S S; Yu, B; Zhou, X J; Rao, Q

    2017-01-08

    Objective: To investigate the clinicopathological features of mammary analogue secretory carcinoma (MASC) of salivary glands, and its diagnosis, differential diagnosis, immunohistochemistry and molecular pathology. Methods: Seventeen cases of MASC were enrolled, with 9 cases of salivary acinar cell carcinoma and 18 cases of adenoid cystic carcinoma as control groups from Nanjing General Hospital from 1997 to 2014 were included in this retrospective study, combined with immunohistochemistry and molecular detection of ETV6-NTRK3 gene fusion. All cases were histologically reviewed with immunohistochemical staining (EnVision) for S-100 protein, SOX10, GATA3, CD117 expression in each group. Fluorescence in situ hybridization (FISH) was used to detect the ETV6-NTRK3 gene fusion. Results: The age of MASC patients ranged from 27 to 74 years with mean age of 47 and ratio of male and female was 4∶3. All cases showed infiltrative growth and diverse cytology and histology, including lobular (8 cases), cystic papillary (3 cases), cribriform mixed with papillary and glandular structures (6 cases) at various proportions. Some tumors of MASC also exhibited solid growth areas with occasional microcystic honeycombed pattern composed of small cysts merged into larger cysts resembling thyroid follicles. S-100 protein and SOX10 were strongly positive in all MASC cases (17/17). In addition, there was insignificant positivity for GATA3 (3/17) and CD117 (4/17). ETV6 gene fusion detection was informative in 12 MASC cases by FISH with 10 positive cases and 2 negative cases. Conclusions: Combined immunohistochemical positivity of S-100 protein, CD117 and SOX10 are useful in the diagnosis and differential diagnosis of MASC. FISH detection of ETV6-NTRK3 fusion offers an additional molecular diagnostic marker for the diagnosis.

  10. Quantitative Assessment of Mouse Mammary Gland Morphology Using Automated Digital Image Processing and TEB Detection.

    Science.gov (United States)

    Blacher, Silvia; Gérard, Céline; Gallez, Anne; Foidart, Jean-Michel; Noël, Agnès; Péqueux, Christel

    2016-04-01

    The assessment of rodent mammary gland morphology is largely used to study the molecular mechanisms driving breast development and to analyze the impact of various endocrine disruptors with putative pathological implications. In this work, we propose a methodology relying on fully automated digital image analysis methods including image processing and quantification of the whole ductal tree and of the terminal end buds as well. It allows to accurately and objectively measure both growth parameters and fine morphological glandular structures. Mammary gland elongation was characterized by 2 parameters: the length and the epithelial area of the ductal tree. Ductal tree fine structures were characterized by: 1) branch end-point density, 2) branching density, and 3) branch length distribution. The proposed methodology was compared with quantification methods classically used in the literature. This procedure can be transposed to several software and thus largely used by scientists studying rodent mammary gland morphology.

  11. Localization of carbonic anhydrase in the goat mammary gland during involution and lactogenesis.

    Science.gov (United States)

    Cvek, K; Dahlborn, K; Ridderstråle, Y

    1998-02-01

    The aim of this study was to determine whether carbonic anhydrase (CA) activity in goat mammary capillaries is regulated mainly by local or systemic mechanisms. One gland was dried before the contralateral gland, and after parturition only one gland was milked. Biopsies were taken from the mammary glands of three goats at 14 d intervals during involution and the start of the following lactation. A histochemical method was used to visualize sites of CA activity. To follow the involution process, milk (liquid) samples were taken from both teats each week and analysed for pH and composition. The time course of CA activity disappearance and reappearance in the capillaries was related to changes in milk composition and alveolar area. A dense network of capillaries showing membrane-bound staining for CA was found surrounding the alveoli in the lactating gland. CA activity gradually decreased in the drying gland, although the other gland was being milked. After 8 weeks involution the dried gland had a significantly lower number of stained capillaries than the milked gland. Almost no stained capillaries were found during late pregnancy, when both glands were dried and the tissue growth maximal. During lactation milk pH was 6.6 +/- 0.3 and this increased to 7.0 +/- 0.1 in the course of involution. In the last trimester of pregnancy the pH returned to its lower value, while the mammary gland was devoid of stained capillaries. Therefore, the capillary CA could not have been directly involved in the pH regulation of milk. The CA activity reappeared in the capillaries directly after delivery, but only in the milked gland. Clearly the regulation of CA activity is influenced more by local than by systemic factors and is associated with the metabolic activity of milk secretion.

  12. The effects of cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) on milk lipid synthesis in mammary glands of dairy cows.

    Science.gov (United States)

    Yang, Yang; Lin, Ye; Duan, Xiaoyu; Lv, He; Xing, Weinan; Li, Qingzhang; Gao, Xuejun; Hou, Xiaoming

    2017-05-01

    Adequate lipid synthesis by the mammary gland during lactation is essential for the survival of mammalian offspring. Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) is a lipid droplet-associated protein and functions to promote lipid accumulation and inhibit lipolysis in mice and human adipocytes. However, the function of CIDEC in regulation of milk lipid synthesis in dairy cow mammary gland remains largely unknown. In this study, 6 multiparous Holstein cows (parity = 3) in early lactation were allocated to high-fat milk (milk yield 33.9 ± 2.1 kg/d, milk fat >3.5%, n = 3) and low-fat milk (milk yield 33.7 ± 0.5 kg/d, milk fat milk fat content. Lactating cows were slaughtered at 90 d in milk and mammary tissues were collected to detect CIDEC localization. Immunofluorescence staining of sections of lactating mammary glands with high- and low-fat milk showed that CIDEC was expressed in the cytoplasm of epithelial cells and localized to lipid droplets. Lipid droplets and CIDEC protein were also detected in isolated lactating mammary epithelial cells of dairy cows. Immunostaining of CIDEC in isolated mammary epithelial cells also confirmed its presence in the nucleus. The knockdown of CIDEC in cultured bovine mammary epithelial cells decreased milk lipid content and reduced expression of genes associated with mammary de novo fatty acid synthesis, short- and long-chain intracellular fatty acid activation, triacylglycerol synthesis, and transcription regulation. These genes included those for acetyl-CoA carboxylase (ACC, -60%), fatty acid synthase (FASN, -65%), acyl-CoA synthetase short-chain family member 2 (ACSS2, -50%), acyl-CoA synthetase long-chain family member 1 (ACSL1, -30%), diacylglycerol acyltransferase 1 (DGAT1, -60%), sterol regulatory element-binding protein 1 (SREBP1, -45%), and SREBP cleavage activating protein (SCAP, -66%). Conversely, in cells overexpressing CIDEC, triacylglycerol content was increased, and transcription of

  13. Mammary Gland Ontegeny and Neoplasia in Oxytocin Deficient Mice.

    Science.gov (United States)

    1998-07-01

    be protective. The technical objectives of this proposal as follows. 1) Determine the prevalence of mammary neoplasia in the progeny of MMTV-infected...WT mice to develop mammary neoplasia when exposed in vivo to ovarian steroid hormones. If oxytocin is shown to be an important factor in breast cancer, exogenous oxytocin may be a potential safe, non-toxic measure in its prevention.

  14. Histopathological and in vivo evidence of regucalcin as a protective molecule in mammary gland carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Marques, Ricardo; Vaz, Cátia V.; Maia, Cláudio J. [CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Gomes, Madalena [IPATIMUP, Institute of Molecular Pathology and Immunology, University of Porto, Porto (Portugal); Gama, Adelina [Department of Veterinary Sciences, Animal and Veterinary Science Research Center (CECAV), University of Trás-os-Montes and Alto Douro (UTAD) (Portugal); Alves, Gilberto; Santos, Cecília R. [CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Schmitt, Fernando [IPATIMUP, Institute of Molecular Pathology and Immunology, University of Porto, Porto (Portugal); Medical Faculty, University of Porto, Porto (Portugal); Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto (Canada); Department of Pathology, University Health Network, Toronto (Canada); Socorro, Sílvia, E-mail: ssocorro@fcsaude.ubi.pt [CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal)

    2015-01-15

    Regucalcin (RGN) is a calcium-binding protein, which has been shown to be underexpressed in cancer cases. This study aimed to determine the association of RGN expression with clinicopathological parameters of human breast cancer. In addition, the role of RGN in malignancy of mammary gland using transgenic rats overexpressing the protein (Tg-RGN) was investigated. Wild-type (Wt) and Tg-RGN rats were treated with 7,12-dimethylbenz[α]anthracene (DMBA). Carcinogen-induced tumors were histologically classified and the Ki67 proliferation index was estimated. Immunohistochemistry analysis showed that RGN immunoreactivity was negatively correlated with the histological grade of breast infiltrating ductal carcinoma suggesting that progression of breast cancer is associated with loss of RGN. Tg-RGN rats displayed lower incidence of carcinogen-induced mammary gland tumors, as well as lower incidence of invasive forms. Moreover, higher proliferation was observed in non-invasive tumors of Wt animals comparatively with Tg-RGN. Overexpression of RGN was associated with diminished expression of cell-cycle inhibitors and increased expression of apoptosis inducers. Augmented activity of apoptosis effector caspase-3 was found in the mammary gland of Tg-RGN. RGN overexpression protected from carcinogen-induced mammary gland tumor development and was linked with reduced proliferation and increased apoptosis. These findings indicated the protective role of RGN in the carcinogenesis of mammary gland. - Highlights: • RGN immunoreactivity was negatively correlated with breast cancer differentiation. • Transgenic overexpression of RGN diminished incidence of carcinogen-induced tumors. • Transgenic overexpression of RGN restricted proliferation and fostered apoptosis. • RGN has a protective role in the carcinogenesis of mammary gland.

  15. Effects of Chronic Genistein Treatment in Mammary Gland, Uterus, and Vagina

    Science.gov (United States)

    Rimoldi, Guillermo; Christoffel, Julie; Seidlova-Wuttke, Dana; Jarry, Hubertus; Wuttke, Wolfgang

    2007-01-01

    Background The isoflavone genistein (GEN) is found in soy (Glycine max) and red clover (Trifolium pratense). The estrogenic activity of GEN is known, and it is widely advertised as a phytoestrogen useful in alleviating climacteric complaints and other postmenopausal disorders. Knowledge of effects of long-term administration of GEN in laboratory animals is scarce, and effects in the uterus and mammary gland after long-term administration have not been studied. The uterus and mammary gland are known to be negatively influenced by estrogens used in hormone therapy. Objectives We administered two doses of GEN [mean daily uptake 5.4 (low) or 54 mg/kg (high) body weight (bw)] orally over a period of 3 months to ovariectomized (ovx) rats and compared the effects with a treatment with two doses of 17β-estradiol [E2; 0.17 (low) or 0.7 mg/kg bw (high)]. Mammary glands, vaginae, and uteri were investigated morphologically and immunohistochemically. We quantified the expression of proliferating cell nuclear antigen (PCNA) and progesterone receptor (PR) in the mammary gland. Results In rats treated with either of the E2 doses or the high GEN dose, we found increased uterine weight, and histologic analysis showed estrogen-induced features in the uteri. In vaginae, either E2 dose or GEN high induced hyperplastic epithelium compared with the atrophic controls. In the mammary gland, E2 (either dose) or GEN increased proliferation and PR expression. Serum levels of luteinizing hormone were decreased by E2 (both doses) but not by GEN. Conclusions In summary, E2 and GEN share many effects in the studied organs, particularly in the vagina, uterus, and mammary gland but not in the hypothalamo/pituitary unit. PMID:18174952

  16. Signalling pathways implicated in early mammary gland morphogenesis and breast cancer.

    Directory of Open Access Journals (Sweden)

    Beatrice Howard

    2006-08-01

    Full Text Available Specification of mammary epithelial cell fate occurs during embryogenesis as cells aggregate to form the mammary anlage. Within the embryonic mammary bud, a population of epithelial cells exists that will subsequently proliferate to form a ductal tree filling the stromal compartment, and which can produce milk upon terminal differentiation after birth. Subsequently, these structures can be remodelled and returned to a basal state after weaning before regenerating in future pregnancies. The plasticity of the mammary epithelial cell, and its responsiveness to hormone receptors, facilitates this amazing biological feat, but aberrant signalling may also result in unintended consequences in the form of frequent malignancies. Reflecting this intimate connection, a considerable number of signalling pathways have been implicated in both mammary gland morphogenesis and carcinogenesis.

  17. Ghrelin is expressed in the pregnant mammary glands of dairy goats and promotes the cell proliferation of mammary epithelial cells.

    Science.gov (United States)

    Zhang, Wenlong; Zhang, Zelin; Chen, Jinxuan; Tong, Dewen

    2018-01-20

    Little is known about ghrelin's effects on cell proliferation in pregnant mammary epithelial cells (MECs) even though it is known 4 to be a mitogen for a variety of other cell types. The objectives of this study were to evaluate the expression and localization of ghrelin and its functional receptor, GHSR-1a, in the mammary glands of dairy goats during pregnancy and to investigate the direct role of ghrelin in cell proliferation of primary cultured MECs. Compared to the early stage (days 30) of pregnancy, the abundance of transcripts and protein of ghrelin and GHSR-1a were significantly greater in mid- and late-phases (between days 90 and days 120) of pregnancy (p < 0.05). Immunohistochemistry analysis showed that ghrelin and GHSR-1a were predominantly localized in the alveolar and ductal mammary epithelial cells at various stages of pregnancy. In our in vitro experiments, ghrelin induced a dose- and time- dependent promotory effect on cell proliferation of MECs. At the dose of 103 pg/mL treatment 24 h, ghrelin augmented the expression of proliferation-related peptides (PCNA and cyclin B1). Furthermore, ghrelin promoted the expression of prolactin (PRL) and GHSR-1a in cultured MECs. Additionally, the the stimulatory effects of ghrelin were blocked by D-Lys3-GHRP6, a selective antagonist of GHSR-1a. As the temporal changes in ghrelin and GHSR-1a expression in pregnant goat mammary glands coincided with the mammary growth and development during the pregnancy, activation of GHSR-1a signal transduction pathways by ghrelin may play a direct role in the regulation of mammary growth in dairy goats. Copyright © 2018. Published by Elsevier Inc.

  18. STAT5 deletion in macrophages alters ductal elongation and branching during mammary gland development.

    Science.gov (United States)

    Brady, Nicholas J; Farrar, Michael A; Schwertfeger, Kathryn L

    2017-08-01

    Macrophages are required for proper mammary gland development and maintaining tissue homeostasis. However, the mechanisms by which macrophages regulate this process remain unclear. Here, we identify STAT5 as an important regulator of macrophage function in the developing mammary gland. Analysis of mammary glands from mice with STAT5-deficient macrophages demonstrates delayed ductal elongation, enhanced ductal branching and increased epithelial proliferation. Further analysis reveals that STAT5 deletion in macrophages leads to enhanced expression of proliferative factors such as Cyp19a1/aromatase and IL-6. Mechanistic studies demonstrate that STAT5 binds directly to the Cyp19a1 promoter in macrophages to suppress gene expression and that loss of STAT5 results in enhanced stromal expression of aromatase. Finally, we demonstrate that STAT5 deletion in macrophages cooperates with oncogenic initiation in mammary epithelium to accelerate the formation of estrogen receptor (ER)-positive hyperplasias. These studies establish the importance of STAT5 in macrophages during ductal morphogenesis in the mammary gland and demonstrate that altering STAT5 function in macrophages can affect the development of tissue-specific disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Genes regulating lipid and protein metabolism are highly expressed in mammary gland of lactating dairy goats.

    Science.gov (United States)

    Shi, Hengbo; Zhu, Jiangjiang; Luo, Jun; Cao, Wenting; Shi, Huaiping; Yao, Dawei; Li, Jun; Sun, Yuting; Xu, Huifen; Yu, Kang; Loor, Juan J

    2015-05-01

    Dairy goats serve as an important source of milk and also fulfill agricultural and economic roles in developing countries. Understanding the genetic background of goat mammary gland is important for research on the regulatory mechanisms controlling tissue function and the synthesis of milk components. We collected tissue at four different stages of goat mammary gland development and generated approximately 25 GB of data from Illumina de novo RNA sequencing. The combined reads were assembled into 51,361 unigenes, and approximately 60.07 % of the unigenes had homology to other proteins in the NCBI non-redundant protein database (NR). Functional classification through eukaryotic Ortholog Groups of Protein (KOG), gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the unigenes from goat mammary glands are involved in a wide range of biological processes and metabolic pathways, including lipid metabolism and lactose metabolism. The results of qPCR revealed that genes encoding FABP3, FASN, SCD, PLIN2, whey proteins (LALBA and BLG), and caseins (CSN1S1, CSN1S2, CSN2 and CSN3) at 100 and 310 days postpartum increased significantly compared with the non-lactating period. In addition to their role in lipid and protein synthesis, the higher expression at 310 days postpartum could contribute to mammary cell turnover during pregnancy. In conclusion, this is the first study to characterize the complete transcriptome of goat mammary glands and constitutes a comprehensive genomic resource available for further studies of ruminant lactation.

  20. Functional receptors for atrial natriuretic peptide in the rat mammary gland during lactation.

    Science.gov (United States)

    Cvek, K; Ridderstråle, Y; Gerstberger, R

    1998-05-01

    The present study was undertaken: 1) to localize and characterize atrial natriuretic peptide (ANP) receptors in the rat mammary gland; and 2) to elucidate ANP-induced cellular formation of cyclic GMP (cGMP) and alterations in alveolar morphology during both early and late lactation. Receptor autoradiography, employing rat-specific [125I]ANP as radioligand, demonstrated binding sites in the secretory tissue and larger blood vessels of the mammary gland. Binding of [125I]rANP to membrane fractions was completely displaced by unlabeled ANP and brain natriuretic peptide. C-type natriuretic peptide and cANP(4-23) revealed limited competition with radiolabeled ANP only during early lactation, indicating a more heterogeneous receptor population at that time. Systemically administered ANP induced cGMP formation in the alveolar epithelium, as shown with immunohistochemistry, and increased mammary tissue cGMP concentrations in vivo throughout the lactation period. Image analysis revealed enlargement of alveolar (but not epithelial) cell area after ANP stimulation in late lactation, suggesting altered alveolar filling or myoepithelial cell relaxation. These results indicate that ANP induces biological effects in the rat mammary gland through specific ANP-A receptor interaction with subsequent intracellular cGMP formation. ANP may therefore play a regulatory role in the control of mammary gland blood supply and secretory function.

  1. The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and Tumor Development

    Science.gov (United States)

    2015-09-01

    Histo- and pathological analysis revealed that, unlike homogeneous and well differentiated T47D-Sh-Ctrl. mammary tumors, T47D-Sh-BRCA1 tumors were...AWARD NUMBER: W81XWH-13-1-0282 TITLE: The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and Tumor...2014 - 31 Aug 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER The Role of BRCA1 in Suppressing Epithelial-Mesenchymal Transition in Mammary Gland and

  2. Prolactin-like activity of anti-prolactin receptor antibodies on casein and DNA synthesis in the mammary gland.

    OpenAIRE

    Djiane, J; Houdebine, L M; Kelly, P A

    1981-01-01

    Prolactin receptors were partially purified from rabbit mammary gland membranes by using an affinity chromatography technique. Antibodies against this prolactin receptor preparation were obtained in guinea pig and sheep. Both antisera were able to inhibit the binding of 125I-labeled ovine prolactin to rabbit mammary gland membranes. When added to culture media of rabbit mammary explants, the anti-prolactin receptor antiserum inhibited the capacity of prolactin to initiate casein synthesis and...

  3. A paracrine role for the epithelial progesterone receptor in mammary gland development

    OpenAIRE

    Brisken, Cathrin; Park, Sissela; Vass, Tibor; Lydon, John P.; O’Malley, Bert W.; Weinberg, Robert A.

    1998-01-01

    Recently generated progesterone receptor (PR)-negative (PR−/−) mice provide an excellent model for dissecting the role of progesterone in the development of the mammary gland during puberty and pregnancy. However, the full extent of the mammary gland defect in these mice caused by the absence of the PR cannot be assessed, because PR−/− mice do not exhibit estrous cycles and fail to become pregnant. To circumvent this difficulty, we have transplanted PR−/− breasts into wild-type mice, and we h...

  4. Lactogenesis in the rat. Metabolism of uridine diphosphate galactose by mammary gland

    Science.gov (United States)

    Kuhn, N. J.

    1968-01-01

    1. Lactose synthetase activity in the rat mammary gland increases during the last day of pregnancy from an essentially zero value. There is a parallel increase of tissue lactose and of glucose 6-phosphate dehydrogenase activity. 2. Mammary-gland homogenates prepared both before and after parturition hydrolyse the lactose precursors glucose 6-phosphate, glucose 1-phosphate, UDP-glucose, UDP-galactose and also maltose, but not lactose. 3. A role of lactose synthetase as the rate-limiting enzyme for lactose biosynthesis and the possible significance of the hydrolytic activities are discussed with respect to lactogenesis. PMID:5639929

  5. Ultrasound Imaging of Mammary Glands in Dairy Heifers at Different Stages of Growth

    OpenAIRE

    Nishimura, Maki; Yoshida, Tetsuya; El-KHODERY, Sabry; MIYOSHI, Masafumi; FURUOKA, Hidefumi; YASUDA, Jun; MIYAHARA, Kazuro; 古岡, 秀文; 宮原, 和郎

    2011-01-01

    To obtain B-mode ultrasound images of mammary glands in dairy heifers at different stages of growth, 25 clinically normal Holstein heifers were used. The heifers were divided into 5 groups (n=5/group) by stage of their growth: 2-month-old (group 1), 5-month-old (group 2), postpuberty (group 3), mid (group 4), and late (group 5) pregnancy. Furthermore, the sections of mammary glands were observed grossly at postmortem examination in one heifer in each group. Ultrasound images varied with the d...

  6. [Biological implant in single-stage reconstruction of mammary gland for cancer].

    Science.gov (United States)

    Zikiriakhodzhaev, A D; Ermoshchenkova, M V

    2015-01-01

    Brief literature review about features of biological implants application for mammary gland reconstruction is presented in the article. Possible complications after such materials use, first experience of acellular dermal matrix administration for single-stage mammary gland reconstruction in 6 patients with breast cancer are also described. We offered surgical techniques, complications and methods of its treatment. We presented advantages of biological implant use which are consisted in decrease of surgical damage and duration of surgery, opportunity for enlargement of pocket for implant, decrease of pain syndrome.

  7. The mammary gland in small ruminants: major morphological and functional events underlying milk production--a review.

    Science.gov (United States)

    Lérias, Joana R; Hernández-Castellano, Lorenzo E; Suárez-Trujillo, Aridany; Castro, Noemí; Pourlis, Aris; Almeida, André M

    2014-08-01

    The importance of small ruminants to the dairy industry has increased in recent years, especially in developing countries, where it has a high economic and social impact. Interestingly and despite the fact that the mammary gland is the specialised milk production organ, very few authors studied the modifications occurring in the mammary gland through the lactation period in production animals, particularly in the small ruminants, sheep (Ovis aries) and goat (Capra hircus). Nevertheless, understanding the different mammary gland patterns throughout lactation is essential to improve dairy production. In addition, associating these patterns with different milking frequencies, lactation number or different diets is also of high importance, directly affecting the dairy industry. The mammary gland is commonly composed of parenchyma and stroma, which includes the ductal system, with individual proportions of each changing during the different periods and yields in a lactation cycle. Indeed, during late gestation, as well as during early to mid-lactation, mammary gland expansion occurs, with an increase in the number of epithelial cells and lumen area, which leads to increment of the parenchyma tissue, as well as a reduction of stroma, corresponding macroscopically to the increase in mammary gland volume. Throughout late lactation, the mammary gland volume decreases owing to the regression of the secretory structure. In general, common mammary gland patterns have been shown for both goats and sheep throughout the several lactation stages, although the number of studies is limited. The main objective of this manuscript is to review the colostrogenesis and lactogenesis processes as well as to highlight the mammary gland morphological patterns underlying milk production during the lactation cycle for small ruminants, and to describe potential differences between goats and sheep, hence contributing to a better description of mammary gland development during lactation for these

  8. Stem/progenitor cells in non-lactating versus lactating equine mammary gland.

    Science.gov (United States)

    Spaas, Jan H; Chiers, Koen; Bussche, Leen; Burvenich, Christian; Van de Walle, Gerlinde R

    2012-11-01

    The mammary gland is a highly regenerative organ that can undergo multiple cycles of proliferation, lactation, and involution. Based on the facts that (i) mammary stem/progenitor cells (MaSC) are proposed to be the driving forces behind mammary growth and function and (ii) variation exists between mammalian species with regard to physiological and pathological functioning of this organ, we believe that studying MaSC from different mammals is of great comparative interest. Over the years, important data has been gathered on MaSC of men and mice, although knowledge on MaSC in other mammals remains limited. Therefore, the aim of this work was to isolate and characterize MaSC from the mammary gland of horses. Hereby, our salient findings were that the isolated equine cells met the 2 in vitro hallmark properties of stem cells, namely the ability to self-renew and to differentiate into multiple cell lineages. Moreover, the cells were immunophenotyped using markers for CD29, CD44, CD49f, and Ki67. Finally, we propose the mammosphere assay as a valuable in vitro assay to study MaSC during different physiological phases since it was observed that equine lactating mammary gland contains significantly more mammosphere-initiating cells than the inactive, nonlactating gland (a reflection of MaSC self-renewal) and, moreover, that these spheres were significantly larger in size upon initial cultivation (a reflection of progenitor cell proliferation). Taken together, this study not only extends the current knowledge of mammary gland biology, but also benefits the comparative approach to study and compare MaSC in different mammalian species.

  9. Epithelial Xbp1 Is Required for Cellular Proliferation and Differentiation during Mammary Gland Development

    Science.gov (United States)

    Hasegawa, Daisuke; Calvo, Veronica; Avivar-Valderas, Alvaro; Lade, Abigale; Chou, Hsin-I; Lee, Youngmin A.; Farias, Eduardo F.; Aguirre-Ghiso, Julio A.

    2015-01-01

    Xbp1, a key mediator of the unfolded protein response (UPR), is activated by IRE1α-mediated splicing, which results in a frameshift to encode a protein with transcriptional activity. However, the direct function of Xbp1 in epithelial cells during mammary gland development is unknown. Here we report that the loss of Xbp1 in the mammary epithelium through targeted deletion leads to poor branching morphogenesis, impaired terminal end bud formation, and spontaneous stromal fibrosis during the adult virgin period. Additionally, epithelial Xbp1 deletion induces endoplasmic reticulum (ER) stress in the epithelium and dramatically inhibits epithelial proliferation and differentiation during lactation. The synthesis of milk and its major components, α/β-casein and whey acidic protein (WAP), is significantly reduced due to decreased prolactin receptor (Prlr) and ErbB4 expression in Xbp1-deficient mammary epithelium. Reduction of Prlr and ErbB4 expression and their diminished availability at the cell surface lead to reduced phosphorylated Stat5, an essential regulator of cell proliferation and differentiation during lactation. As a result, lactating mammary glands in these mice produce less milk protein, leading to poor pup growth and postnatal death. These findings suggest that the loss of Xbp1 induces a terminal UPR which blocks proliferation and differentiation during mammary gland development. PMID:25713103

  10. The Wnt co-receptor Lrp6 is required for normal mouse mammary gland development.

    Directory of Open Access Journals (Sweden)

    Charlotta Lindvall

    Full Text Available Canonical Wnt signals are transduced through a Frizzled receptor and either the LRP5 or LRP6 co-receptor; such signals play central roles during development and in disease. We have previously shown that Lrp5 is required for ductal stem cell activity and that loss of Lrp5 delays normal mammary development and Wnt1-induced tumorigenesis. Here we show that canonical Wnt signals through the Lrp6 co-receptor are also required for normal mouse mammary gland development. Loss of Lrp6 compromises Wnt/beta-catenin signaling and interferes with mammary placode, fat pad, and branching development during embryogenesis. Heterozygosity for an inactivating mutation in Lrp6 is associated with a reduced number of terminal end buds and branches during postnatal development. While Lrp6 is expressed in both the basal and luminal mammary epithelium during embryogenesis, Lrp6 expression later becomes restricted to cells residing in the basal epithelial layer. Interestingly, these cells also express mammary stem cell markers. In humans, increased Lrp6 expression is associated with basal-like breast cancer. Taken together, our results suggest both overlapping and specific functions for Lrp5 and Lrp6 in the mammary gland.

  11. Inhibiting prolactin by cabergoline accelerates mammary gland remodeling during the early dry period in dairy cows.

    Science.gov (United States)

    Boutinaud, M; Isaka, N; Gandemer, E; Lamberton, P; Wiart, S; Taranilla, A I De Prado; Sordillo, L M; Lollivier, V

    2017-12-01

    The inhibition of prolactin release using cabergoline, a dopamine agonist, is an effective strategy to accelerate the changes in mammary secretion composition after drying-off. The objective of this study was to determine how cabergoline may affect mammary tissue remodeling during early involution. Holstein dairy cows were treated with either a single i.m. administration of 5.6 mg of cabergoline (Velactis, Ceva Santé Animale, Libourne, France, n = 7) or placebo (n = 7) at the time of drying-off. Mammary biopsy samples were collected 1 wk before drying-off (d -6), after 30 h of milk accumulation (d 1), and again 8 d following drying-off (d 8) to determine changes in gene expression, lactoferrin content, and cell turnover. Blood and mammary secretion samples were collected at d -6 and again at d 1, 2, 3, 4, 8, and 14 following the abrupt cessation of lactation to evaluate indicators of blood-milk barrier integrity and other markers of mammary tissue remodeling. Cabergoline induced less SLC2A1, BAX, CAPN2, and IGFBP5 mRNA expression. In contrast, cabergoline did not modify changes in cell proliferation and apoptosis. Following the cessation of lactation, changes in mammary secretion composition (Na+ and K+) and blood lactose concentrations were indicative of a loss in the blood-milk barrier function in both treatment groups. Cabergoline treatment affected only Na+ and K+ concentrations at d 1, suggesting a moderate increase in tight junction permeability. The increase in the activity of MMP9 and in mammary epithelial cell concentration in mammary secretions was greater in cabergoline-treated cows than in control cows, suggesting more mammary tissue remodeling. The increase in lactoferrin immunostaining in the mammary tissue occurred earlier for cabergoline-treated cows than for control cows, and was essentially localized in the stroma. Changes in some key markers of mammary involution suggest that cabergoline accelerates mammary gland remodeling. Thus, a single

  12. Characteristics of rabbit transgenic mammary gland expressing recombinant human factor VIII.

    Science.gov (United States)

    Chrenek, P; Makarevich, A V; Pivko, J; Massanyi, P; Lukac, N

    2009-02-01

    The objective of this research was to compare (i) the content of milk protein and recombinant human factor VIII (rhFVIII) in the milk of transgenic and non-transgenic rabbit females at three lactations and (ii) histological structure, ultrastructural morphology and occurrence of apoptosis in rabbit transgenic and non-transgenic mammary gland during third lactation and involution. Significant differences (t(0.05)) in milk protein content were found between transgenic and non-transgenic at all three lactations. The percentage of apoptotic cells was significantly higher (t(0.01)) in non-transgenic ones compared with transgenic mammary gland tissues (6.5% versus 2.4%) taken at the involution stage. Morphometrical analysis of histological preparations at the involution stage detected a significantly higher (t(0.05)) relative volume of lumen in transgenic animals compared with non-transgenic ones (60.00 versus 46.51%). Ultrastructural morphology of the transgenic mammary gland epithelium at the involution stage revealed an increased relative volume of protein globules (t(0.05)); at the lactation stage, a significantly higher volume of mitochondria (13.8%) compared with the non-transgenic (9.8%) ones was observed. These results, although revealing differences in some parameters of ultrastructure and histology, indicate no harmful effect of the mouse whey acid protein-hFVIII transgene expression on the state of mammary gland of transgenic rabbit females.

  13. Mixtures of environmentally relevant endocrine disrupting chemicals affect mammary gland development in female and male rats

    DEFF Research Database (Denmark)

    Mandrup, Karen Riiber; Johansson, Hanna Katarina Lilith; Boberg, Julie

    2015-01-01

    Estrogenic chemicals are able to alter mammary gland development in female rodents, but little is known on the effects of anti-androgens and mixtures of endocrine disrupting chemicals (EDCs) with dissimilar modes of action. Pregnant rat dams were exposed during gestation and lactation to mixtures...

  14. Estrogenic plant extracts reverse weight gain and fat accumulation without causing mammary gland or uterine proliferation.

    Directory of Open Access Journals (Sweden)

    Elise F Saunier

    Full Text Available Long-term estrogen deficiency increases the risk of obesity, diabetes and metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing estrogens might prevent these conditions, but its prolonged use increases the risk of breast cancer, as wells as endometrial cancer if used without progestins. Animal studies indicate that beneficial effects of estrogens in adipose tissue and adverse effects on mammary gland and uterus are mediated by estrogen receptor alpha (ERα. One strategy to improve the safety of estrogens to prevent/treat obesity, diabetes and metabolic syndrome is to develop estrogens that act as agonists in adipose tissue, but not in mammary gland and uterus. We considered plant extracts, which have been the source of many pharmaceuticals, as a source of tissue selective estrogens. Extracts from two plants, Glycyrrhiza uralensis (RG and Pueraria montana var. lobata (RP bound to ERα, activated ERα responsive reporters, and reversed weight gain and fat accumulation comparable to estradiol in ovariectomized obese mice maintained on a high fat diet. Unlike estradiol, RG and RP did not induce proliferative effects on mammary gland and uterus. Gene expression profiling demonstrated that RG and RP induced estradiol-like regulation of genes in abdominal fat, but not in mammary gland and uterus. The compounds in extracts from RG and RP might constitute a new class of tissue selective estrogens to reverse weight gain, fat accumulation and metabolic syndrome in postmenopausal women.

  15. Estrogenic plant extracts reverse weight gain and fat accumulation without causing mammary gland or uterine proliferation.

    Science.gov (United States)

    Saunier, Elise F; Vivar, Omar I; Rubenstein, Andrea; Zhao, Xiaoyue; Olshansky, Moshe; Baggett, Scott; Staub, Richard E; Tagliaferri, Mary; Cohen, Isaac; Speed, Terence P; Baxter, John D; Leitman, Dale C

    2011-01-01

    Long-term estrogen deficiency increases the risk of obesity, diabetes and metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing estrogens might prevent these conditions, but its prolonged use increases the risk of breast cancer, as wells as endometrial cancer if used without progestins. Animal studies indicate that beneficial effects of estrogens in adipose tissue and adverse effects on mammary gland and uterus are mediated by estrogen receptor alpha (ERα). One strategy to improve the safety of estrogens to prevent/treat obesity, diabetes and metabolic syndrome is to develop estrogens that act as agonists in adipose tissue, but not in mammary gland and uterus. We considered plant extracts, which have been the source of many pharmaceuticals, as a source of tissue selective estrogens. Extracts from two plants, Glycyrrhiza uralensis (RG) and Pueraria montana var. lobata (RP) bound to ERα, activated ERα responsive reporters, and reversed weight gain and fat accumulation comparable to estradiol in ovariectomized obese mice maintained on a high fat diet. Unlike estradiol, RG and RP did not induce proliferative effects on mammary gland and uterus. Gene expression profiling demonstrated that RG and RP induced estradiol-like regulation of genes in abdominal fat, but not in mammary gland and uterus. The compounds in extracts from RG and RP might constitute a new class of tissue selective estrogens to reverse weight gain, fat accumulation and metabolic syndrome in postmenopausal women.

  16. Low-dose effects of bisphenol A on mammary gland development in rats

    DEFF Research Database (Denmark)

    Egebjerg, Karen Mandrup; Boberg, Julie; Isling, Louise Krag

    2016-01-01

    Bisphenol A (BPA) is widely used in food contact materials, toys, and other products. Several studies have indicated that effects observed at doses near human exposure levels may not be observed at higher doses. Many studies have shown effects on mammary glands at low doses of BPA, however, because...

  17. New methods in mammary gland development and cancer: proteomics, epigenetics, symmetric division and metastasis.

    Science.gov (United States)

    Bentires-Alj, Mohamed; Glukhova, Marina; Hynes, Nancy; Vivanco, Maria

    2012-07-19

    The European Network for Breast Development and Cancer (ENBDC) meeting on 'Methods in Mammary Gland Development and Cancer' has become an annual international rendezvous for scientists with interests in the normal and neoplastic breast. The fourth meeting in this series, held in April in Weggis, Switzerland, focused on proteomics, epigenetics, symmetric division, and metastasis.

  18. Mammary Analogue Secretory Carcinoma (MASC of the salivary gland: A new tumor entity

    Directory of Open Access Journals (Sweden)

    Ivan Damjanov

    2016-08-01

    Full Text Available Mammary analogue secretory carcinoma (MASC is a recently described low-grade malignant tumor of the salivary glands, biologically and morphologically equivalent to secretory breast carcinoma. We give a brief overview of this new entity, including morphological, immunohistochemical, molecular-genetic, clinical, epidemiologic features, differential diagnosis, and outcome results.

  19. Mammary Analogue Secretory Carcinoma (MASC) of the salivary gland: A new tumor entity.

    Science.gov (United States)

    Damjanov, Ivan; Skenderi, Faruk; Vranic, Semir

    2016-08-02

    Mammary analogue secretory carcinoma (MASC) is a recently described low-grade malignant tumor of the salivary glands, biologically and morphologically equivalent to secretory breast carcinoma. We give a brief overview of this new entity, including morphological, immunohistochemical, molecular-genetic, clinical, epidemiologic features, differential diagnosis, and outcome results.

  20. Vitamin D Pathway Status and the Identification of Target Genes in the Mouse Mammary Gland

    Science.gov (United States)

    2014-11-01

    not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE November 2014 2. REPORT TYPE...1):e1483. 13 Anderson RR. Relation between mammary gland development and body weight. Journal of Dairy Science 1976; 59(8):1518-1521. 19

  1. Mammary analogue secretory carcinoma: update on a new diagnosis of salivary gland malignancy.

    Science.gov (United States)

    Sethi, Roshan; Kozin, Elliott; Remenschneider, Aaron; Meier, Josh; VanderLaan, Paul; Faquin, William; Deschler, Daniel; Frankenthaler, Robert

    2014-01-01

    To review the known histopathologic findings and clinical behavior of mammary analogue secretory carcinoma (MASC). PubMed. Literature search using the terms "Mammary analogue secretory carcinoma," "Mammary analog secretory carcinoma," and "MASC" to identify all relevant publications. MASC is an unusual and rare malignant salivary gland tumor first described in 2010. It shares histologic, immunohistochemical, and genetic features with secretory carcinoma of the breast. The clinical behavior of MASC ranges from slowly growing tumors that infrequently recur after surgical resection to aggressive tumors that cause widespread metastasis and death. Many cases of MASC were discovered in archived cases previously classified as acinic cell carcinoma, mucoepidermoid carcinoma, and adenocarcinoma not otherwise specified. MASC is a newly recognized variant of salivary gland malignancy. Further research is needed to better delineate its overall prevalence and to define an appropriate treatment algorithm for this new clinical entity. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  2. Developmental expression patterns and regulation of connexins in the mouse mammary gland: expression of connexin30 in lactogenesis.

    Science.gov (United States)

    Talhouk, Rabih S; Elble, Randolph C; Bassam, Rola; Daher, Mariam; Sfeir, Agnel; Mosleh, Lina Abi; El-Khoury, Hilda; Hamoui, Samar; Pauli, Bendicht U; El-Sabban, Marwan E

    2005-01-01

    The mammary gland reaches a fully differentiated phenotype at lactation, a stage characterized by the abundant expression of beta-casein. We have investigated the expression and regulation of gap junction proteins (connexins, Cx) during the various developmental stages of mouse mammary gland. Immunohistochemical analysis, with specific antibodies, reveals that Cx26 and Cx32 are expressed and confined to the cell borders of luminal epithelial cells in all developmental stages of the gland. Cx26 and Cx32 expression, at the mRNA and protein levels, increases in pregnancy and peaks in lactation. Whereas Cx43 mRNA decreases in pregnancy and lactation, the functional activity of Cx43 protein, which has been localized to myoepithelial cells, is regulated (through phosphorylation) during pregnancy and peaks during lactation. Cx30 mRNA and proteins have, for the first time, been detected in mammary gland epithelia. Using reverse transcription/polymerase chain reaction and sequencing techniques, we show that Cx30 is abundant in pregnant and lactating mammary gland. Cx30 protein levels have not been detected in the mammary gland prior to day 15 of pregnancy, whereas maximum expression occurs at the onset of lactation. In mouse mammary cells in culture, Cx30 is epithelial-cell-specific and is induced by lactogenic hormones. These data identify a novel player in mammary differentiation and suggest a potential role for Cx30 in the fully differentiated gland.

  3. Mammary Gland Evaluation in Juvenile Toxicity Studies: Temporal Developmental Patterns in the Male and Female Harlan Sprague Dawley Rat

    Science.gov (United States)

    Filgo, Adam J.; Foley, Julie F.; Puvanesarajah, Samantha; Borde, Aditi R.; Midkiff, Bentley R.; Reed, Casey E.; Chappell, Vesna A.; Alexander, Lydia B.; Borde, Pretish R.; Troester, Melissa A.; Hayes Bouknight, Schantel A.; Fenton, Suzanne E.

    2016-01-01

    There are currently no reports describing mammary gland development in the Harlan Sprague Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were to empower the NTP, contract labs and other researchers in understanding and interpretation of chemical effects in this rat strain. To delineate similarities/differences between the female and male mammary gland, data were compiled starting on embryonic day 15.5 through postnatal day 70. Mammary gland whole mounts, histology sections, and immunohistochemically-stained tissues for estrogen, progesterone and androgen receptors were evaluated in both sexes; qualitative and quantitative differences are highlighted using a comprehensive visual timeline. Research on endocrine disrupting chemicals in animal models has highlighted chemically-induced mammary gland anomalies which may potentially impact human health. In order to investigate these effects within the HSD strain, 2,3,7,8-tetrachlorodibenzo p-dioxin, diethylstilbestrol or vehicle control was gavage dosed on gestation day 15 and 18 to demonstrate delayed, accelerated and control mammary gland growth in offspring, respectively. We provide illustrations of normal and chemically altered mammary gland development in HSD male and female rats to help inform researchers unfamiliar with the tissue and may facilitate enhanced evaluation of both male and female mammary glands in juvenile toxicity studies. PMID:27613106

  4. Conditional Wwox deletion in mouse mammary gland by means of two Cre recombinase approaches.

    Directory of Open Access Journals (Sweden)

    Brent W Ferguson

    Full Text Available Loss of WWOX expression has been reported in many different cancers including breast cancer. Elucidating the function of this gene in adult tissues has not been possible with full Wwox knockout models. Here we characterize the first conditional models of Wwox ablation in mouse mammary epithelium utilizing two transgenic lines expressing Cre recombinase, keratin 5-Cre (BK5-Cre and MMTV-Cre. In the BK5-Cre model we observed very efficient Wwox ablation in KO mammary glands. However, BK5-Cre Wwox KO animals die prematurely for unknown reasons. In the MMTV-Cre model we observed significant ablation of Wwox in mammary epithelium with no effect on survival. In both of these models we found that Wwox deletion resulted in impaired mammary branching morphogenesis. We demonstrate that loss of Wwox is not carcinogenic in our KO models. Furthermore, no evidence of increase proliferation or development of premalignant lesions was observed. In none of the models did loss of a single Wwox allele (i.e. haploinsufficiency have any observable phenotypic effect in mammary gland. To better understand the function of Wwox in the mammary gland, transcriptome profiling was performed. We observed that Wwox ablation results in the deregulation of genes involved in various cellular processes. We found that expression of the non-canonical Wnt ligand, Wnt5a, was significantly upregulated in Wwox KO mammary epithelium. Interestingly, we also determined that components of the Jak/Stat3 signaling pathway were upregulated in KO mice and this correlated with a very robust increase in phospho-Stat3 signaling, which warrants further testing. Even though the loss of Wwox expression in breast and other cancers is very well documented, our findings suggest that Wwox does not act as a classical tumor suppressor as previously thought.

  5. Transcriptome analysis of the mammary gland from GH transgenic goats during involution.

    Science.gov (United States)

    Lin, Jian; Bao, Ze Kun; Zhang, Qiang; Hu, Wei Wei; Yu, Qing Hua; Yang, Qian

    2015-07-10

    Mammary glands are organs for milk production in female mammals. Growth hormone (GH) is known to affect the growth and development of the mammary gland, as well as to increase milk production in dairy goats. This study performed a comprehensive expression profiling of genes expressed in the mammary gland of early involution GH transgenic (n=4) and non-transgenic goats (n=4) by RNA sequencing. RNA was extracted from mammary gland tissues collected at day 3 of involution. Gene expression analysis was conducted by Illumina RNA sequencing and sequence reads were assembled and analyzed using TopHat. FPKM (fragments per kilobase of exon per million) values were analyzed for differentially expressed genes using the Cufflinks package. Gene ontology analysis of differentially expressed genes was categorized using agriGO, while KEGG pathway analysis was performed with the online KEGG automatic annotation server. Our results revealed that 75% of NCBI goat annotated genes were expressed during early involution. A total of 18,323 genes were expressed during early involution in GH transgenic goats, compared with 18,196 expressed genes during early involution of non-transgenic goats. In these expressed genes, the majority (17,589) were ubiquitously expressed in GH transgenic and non-transgenic goats. However, there were 745 differentially expressed genes, 421 of which were upregulated and 324 were downregulated in GH transgenic goats. GO and KEGG pathway analysis showed that these genes were involved in mammary gland physiology, including cell adhesion molecules, ECM-receptor interaction, Jak-STAT signaling pathway, and fat metabolism. Our results demonstrated that the GH receptor was strongly affected in GH transgenic goats, which may activate the IGF-1/Stat3 signaling pathway. Overall, our study provided a global view of the transcriptome during involution of GH transgenic and non-transgenic goats, which increases our understanding of the biology of involution in the goat

  6. Histological analysis of low dose NMU effects in the rat mammary gland

    Directory of Open Access Journals (Sweden)

    Sonnenschein Carlos

    2009-08-01

    Full Text Available Abstract Background Our objective was to assess the histological changes in mammary glands of the female Wistar-Furth rat as a result of low dose exposure to N-nitrosomethylurea (NMU. Methods Groups of 30–40 virgin female rats of between 49–58 days old received a single injection of 10, 20, 30 or 50 mg NMU/kg body weight (BW. A group of 10 control rats received 0.9% NaCl solution only. The formation of palpable mammary gland tumors was assessed weekly and, upon sacrifice at 12, 22 and 25–30 weeks after treatment, we performed a comprehensive histological analysis of all mammary gland lesions and tumors. Results Alongside the predicted increase in tumor number and decrease in tumor latency with increasing NMU dose, we observed a number of microscopic lesions and other epithelial abnormalities in the mammary glands for all NMU doses. Two types of non-neoplastic histological changes were observed in rats exposed to 10 or 20 mg NMU/kg BW: namely, (i an increase in the number of acinar structures often accompanied by secretion into the lumen which is normally associated with pregnancy and lactation, and (ii an increase in the number of epithelial cells sloughed into the lumen of the epithelial ducts. Conclusion This study establishes a baseline for low-dose exposure and defines the histological features in the mammary gland resulting from NMU exposure. Furthermore, this system provides an ideal platform for evaluating the relative susceptibility of animals protected from, or predisposed to, developing cancer through environmental influences.

  7. Columnar cell lesions of the canine mammary gland: pathological features and immunophenotypic analysis

    Directory of Open Access Journals (Sweden)

    Cassali Geovanni D

    2010-02-01

    Full Text Available Abstract Background It has been suggested that columnar cell lesions indicate an alteration of the human mammary gland involved in the development of breast cancer. They have not previously been described in canine mammary gland. The aim of this paper is describe the morphologic spectrum of columnar cell lesions in canine mammary gland specimens and their association with other breast lesions. Methods A total of 126 lesions were subjected to a comprehensive morphological review based upon the human breast classification system for columnar cell lesions. The presence of preinvasive (epithelial hyperplasia and in situ carcinoma and invasive lesions was determined and immunophenotypic analysis (estrogen receptor (ER, progesterone receptor (PgR, high molecular weight cytokeratin (34βE-12, E-cadherin, Ki-67, HER-2 and P53 was perfomed. Results Columnar cell lesions were identified in 67 (53.1% of the 126 canine mammary glands with intraepithelial alterations. They were observed in the terminal duct lobular units and characterized at dilated acini may be lined by several layers of columnar epithelial cells with elongated nuclei. Of the columnar cell lesions identified, 41 (61.2% were without and 26 (38.8% with atypia. Association with ductal hyperplasia was observed in 45/67 (67.1%. Sixty (89.5% of the columnar cell lesions coexisted with neoplastic lesions (20 in situ carcinomas, 19 invasive carcinomas and 21 benign tumors. The columnar cells were ER, PgR and E-cadherin positive but negative for cytokeratin 34βE-12, HER-2 and P53. The proliferation rate as measured by Ki-67 appeared higher in the lesions analyzed than in normal TDLUs. Conclusions Columnar cell lesions in canine mammary gland are pathologically and immunophenotypically similar to those in human breast. This may suggest that dogs are a suitable model for the comparative study of noninvasive breast lesions.

  8. Lgr5-Expressing Cells Are Sufficient and Necessary for Postnatal Mammary Gland Organogenesis

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    Vicki Plaks

    2013-01-01

    Full Text Available Mammary epithelial stem cells are vital to tissue expansion and remodeling during various phases of postnatal mammary development. Basal mammary epithelial cells are enriched in Wnt-responsive cells and can reconstitute cleared mammary fat pads upon transplantation into mice. Lgr5 is a Wnt-regulated target gene and was identified as a major stem cell marker in the small intestine, colon, stomach, and hair follicle, as well as in kidney nephrons. Here, we demonstrate the outstanding regenerative potential of a rare population of Lgr5-expressing (Lgr5+ mammary epithelial cells (MECs. We found that Lgr5+ cells reside within the basal population, are superior to other basal cells in regenerating functional mammary glands (MGs, are exceptionally efficient in reconstituting MGs from single cells, and exhibit regenerative capacity in serial transplantations. Loss-of-function and depletion experiments of Lgr5+ cells from transplanted MECs or from pubertal MGs revealed that these cells are not only sufficient but also necessary for postnatal mammary organogenesis.

  9. Large lipid-rich mammary analogue secretory carcinoma of parotid gland: An unusual case

    Directory of Open Access Journals (Sweden)

    Prashant Joshi

    2015-01-01

    Full Text Available Mammary analogue secretory carcinoma (MASC of the salivary gland is a malignant tumor which bears morphologic, immunohistochemical and molecular features similar to those of mammary secretory carcinoma. The tumor is considered as a low-grade malignancy perhaps slightly more aggressive than acinic cell carcinoma. High-grade transformation with recurrences, regional nodal involvement, metastases, and cancer-related death has been reported in a few cases. We report an unusual case of large MASC of the parotid gland in a young patient without regional lymph node involvement. To the best of our knowledge till date such a large MASC of the salivary gland has not been reported in the English literature.

  10. Effect of the Ketone Body Beta-Hydroxybutyrate on the Innate Defense Capability of Primary Bovine Mammary Epithelial Cells.

    Science.gov (United States)

    Hillreiner, Maria; Flinspach, Claudia; Pfaffl, Michael W; Kliem, Heike

    2016-01-01

    Negative energy balance and ketosis are thought to cause impaired immune function and to increase the risk of clinical mastitis in dairy cows. The present in vitro study aimed to investigate the effect of elevated levels of the predominant ketone body β-hydroxybutyrate on the innate defense capability of primary bovine mammary epithelial cells (pbMEC) challenged with the mastitis pathogen Escherichia coli (E. coli). Therefore, pbMEC of healthy dairy cows in mid- lactation were isolated from milk and challenged in culture with 3 mM BHBA and E. coli. pbMEC stimulated with E. coli for 6 h or 30 h showed an up-regulation of several innate immune genes, whereas co-stimulation of pbMEC with 3 mM BHBA and E. coli resulted in the down-regulation of CCL2, SAA3, LF and C3 gene expression compared to the challenge with solely the bacterial stimulus. These results indicated that increased BHBA concentrations may be partially responsible for the higher mastitis susceptibility of dairy cows in early lactation. Elevated levels of BHBA in blood and milk during negative energy balance and ketosis are likely to impair innate immune function in the bovine mammary gland by attenuating the expression of a broad range of innate immune genes.

  11. Effect of the Ketone Body Beta-Hydroxybutyrate on the Innate Defense Capability of Primary Bovine Mammary Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Maria Hillreiner

    Full Text Available Negative energy balance and ketosis are thought to cause impaired immune function and to increase the risk of clinical mastitis in dairy cows. The present in vitro study aimed to investigate the effect of elevated levels of the predominant ketone body β-hydroxybutyrate on the innate defense capability of primary bovine mammary epithelial cells (pbMEC challenged with the mastitis pathogen Escherichia coli (E. coli. Therefore, pbMEC of healthy dairy cows in mid- lactation were isolated from milk and challenged in culture with 3 mM BHBA and E. coli. pbMEC stimulated with E. coli for 6 h or 30 h showed an up-regulation of several innate immune genes, whereas co-stimulation of pbMEC with 3 mM BHBA and E. coli resulted in the down-regulation of CCL2, SAA3, LF and C3 gene expression compared to the challenge with solely the bacterial stimulus. These results indicated that increased BHBA concentrations may be partially responsible for the higher mastitis susceptibility of dairy cows in early lactation. Elevated levels of BHBA in blood and milk during negative energy balance and ketosis are likely to impair innate immune function in the bovine mammary gland by attenuating the expression of a broad range of innate immune genes.

  12. Mammary gland stem cells: More puzzles than explanations

    Indian Academy of Sciences (India)

    2012-04-28

    Apr 28, 2012 ... 3238–3243. Jiang S, Lee B-C, Fu Y, Avraham S, Lim B and Avraham HK 2010. Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell dif- ferentiation. PLoS One 5 e9707. Jones C, Mackay A, Grigoriadis A, Cossu A, Reis-Filho JS, Fulford.

  13. Mammary gland chondrosarcoma in a German Shepherd bitch: A ...

    African Journals Online (AJOL)

    Canine mammary tumours are the most common tumours in intact bitches and they constitute about 25% of the neoplasm in this species followed by skin tumours (Benjamin et al.,1999) and their incidence varies from 198 to 622.6 cases per 100,000 dogs per year (Vail and MacEwen,2000). According to Yager et al.(1993) ...

  14. Bovine mammary stem cells: Cell biology meets production agriculture

    Science.gov (United States)

    Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue ...

  15. Mammary Gland Involution Provides a Unique Model to Study the TGF-β Cancer Paradox

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    Qiuchen Guo

    2017-01-01

    Full Text Available Transforming Growth Factor-β (TGF-β signaling in cancer has been termed the “TGF-β paradox”, acting as both a tumor suppresser and promoter. The complexity of TGF-β signaling within the tumor is context dependent, and greatly impacted by cellular crosstalk between TGF-β responsive cells in the microenvironment including adjacent epithelial, endothelial, mesenchymal, and hematopoietic cells. Here we utilize normal, weaning-induced mammary gland involution as a tissue microenvironment model to study the complexity of TGF-β function. This article reviews facets of mammary gland involution that are TGF-β regulated, namely mammary epithelial cell death, immune activation, and extracellular matrix remodeling. We outline how distinct cellular responses and crosstalk between cell types during physiologically normal mammary gland involution contribute to simultaneous tumor suppressive and promotional microenvironments. We also highlight alternatives to direct TGF-β blocking anti-cancer therapies with an emphasis on eliciting concerted microenvironmental-mediated tumor suppression.

  16. Morphological changes induced by testosterone in the mammary glands of female Wistar rats

    Directory of Open Access Journals (Sweden)

    A. Chambô-Filho

    2005-04-01

    Full Text Available Increased levels of androgens in postmenopausal women are considered to be a risk factor for breast cancer. Testosterone, alone or in combination with estrogen, induces epithelial dysplasia and mammary tumors in Noble rats. Since this model of hormone-induced neoplasia has not been reported in other rat strains, we studied the effect of testosterone on the mammary gland morphology of female Wistar rats. Sixty adult, non-castrated, female Wistar rats were implanted in the dorsum midline with a silicone tube containing 50 mg testosterone (testosterone propionate in 30 animals and non-esterified testosterone in the remaining 30 animals and 20 additional animals were implanted with empty tubes and used as control. Five animals per group were killed 30, 60, 90, 120, 150, and 180 days after implantation, and the mammary glands were dissected, fixed and embedded in paraffin. Histological sections were then stained with hematoxylin and eosin and picrosyrius red for collagen visualization. Morphological and morphometric analysis demonstrated ductal proliferation and acinotubular differentiation with secretory activity in all treated animals, peaking at 90 days of androgen exposure. After 90 days the proliferation of acinar epithelial cells was evident, but there was a progressive reduction of secretory differentiation and an increase in intralobular collagen fibers. There was no morphological evidence of dysplastic changes or other pre-neoplastic lesions. Testosterone treatment applied to adult, non-castrated female Wistar rats induced a mammary gland hyperplasia resembling the lactating differentiation, with progressive reduction in secretory differentiation.

  17. Raman spectra of normal and cancerous mouse mammary gland tissue using near infrared excitation energy

    Science.gov (United States)

    Naik, Vaman; Serhatkulu, G. K.; Dai, H.; Shukla, N.; Weber, R.; Thakur, J. S.; Freeman, D. C.; Pandya, A. K.; Auner, G. W.; Naik, R.; Miller, R. F.; Cao, A.; Klein, M. D.; Rabah, R.

    2006-03-01

    Raman spectra of normal mammary gland tissues, malignant mammary gland tumors, and lymph nodes have been recorded using fresh tissue from mice. Tumors were induced in mice by subcutaneously injecting 4T1 BALB/c mammary tumor (a highly malignant) cell line. The Raman spectra were collected using the same tissues that were examined by histopathology for determining the cancerous/normal state of the tissue. Differences in various peak intensities, peak shifts and peak ratios were analyzed to determine the Raman spectral features that differentiate mammary gland tumors from non-tumorous tissue. Tissues that were confirmed by pathology as cancerous (tumors) show several distinctive features in the Raman spectra compared to the spectra of the normal tissues. For example, the cancerous tissues show Raman peaks at 621, 642, 1004, 1032, 1175 and 1208 cm-1 that are assignable to amino acids containing aromatic side-chains such as phenylalanine, tryptophan and tyrosine. Further, the cancerous tissues show a greatly reduced level of phospholipids compared to the normal tissues. The Raman spectral regions that are sensitive to pathologic alteration in the tissue will be discussed.

  18. Physical, laboratory, and microbiological parameters of mammary gland secretions in postpartum does

    Directory of Open Access Journals (Sweden)

    Jefferson Filgueira Alcindo

    2016-04-01

    Full Text Available Mastitis is a multifactorial disease whose prevalence is affected by the type of pathogenic agent involved, the constitution of the animal, and environmental conditions. This study evaluated the physical and laboratory characteristics of colostrum from dairy goats in the postpartum period, and the physical characteristics of the mammary glands in the same period. Of the 71 mammary glands evaluated, 12 were positive for bacterial isolates and the most frequent pathogenic agents were coagulase-negative staphylococci (CNS (n = 11. Median somatic cell counts (SCC in animals positive for bacterial isolates were greater than in animals without bacterial isolates at parturition (696.0 vs. 256.0 x 103 mL –1 and 48 h postpartum (1,350 vs. 437.0 x 103 mL-1. In addition, 34 samples were positive for the California Mastitis Test (CMT; score >1+, indicating a positive relationship between this test and bacterial isolation. Coagulase-negative staphylococci (CNS were the most prevalent pathogenic agents, resulting in increase in SCC. Postpartum changes in mammary secretions were not good predictors of bacterial mastitis. Physical examination of mammary glands did not reveal significant changes for the diagnosis of mastitis in the postpartum period.

  19. Genotoxic exposure during juvenile growth of mammary gland depletes stem cell activity and inhibits Wnt signaling.

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    Kristine S Klos

    Full Text Available Various types of somatic stem cell have been tested for their response to genotoxic exposure, since these cells are likely to be important to regeneration, aging and cancer. In this study, we evaluated the response of mammary stem cells to genotoxic exposure during ductal growth in juveniles. Exposure to the polycyclic aromatic hydrocarbon (DMBA; 7,12 dimethylbenz[a]anthracene had no gross effect on outgrowth and morphogenesis of the ductal tree, or upon lobuloalveolar growth during pregnancy. However, by fat pad assay, we found that mammary stem cell activity was reduced by 80% in glands from adults that were exposed to genotoxins as juveniles. The associated basal cell lineage was depleted. Both basal and luminal cells showed a robust response to genotoxic exposure (including γH2AX phosphorylation, pS(15p53 and pT(68Chk2, with durable hyperproliferation, but little cytotoxicity. Since the phenotype of these glands (low basal cell fraction, low stem cell activity phenocopies mammary glands with loss of function for Wnt signaling, we measured Wnt signaling in genotoxin-exposed glands, and found a durable reduction in the activation of the canonical signaling Wnt receptors, Lrp5/6. Furthermore, when mammary epithelial cells were treated with Wnt3a, DMBA exposure reduced the basal cell population and Lrp activation was ablated. We conclude that during active ductal growth, Wnt-dependent mammary stem cells are sensitized to cell death by genotoxin exposure. Our conclusion may be important for other tissues, since all solid tumor stem cell activities have been shown to be Wnt-dependent to date.

  20. Low-dose effects of bisphenol A on mammary gland development in rats

    DEFF Research Database (Denmark)

    Egebjerg, Karen Mandrup; Boberg, Julie; Isling, Louise Krag

    2016-01-01

    of small number of animals or few doses investigated these data have not been used by EFSA as point of departure for the newly assessed tolerable daily intake (TDI). We performed a study with perinatal exposure to BPA (0, 0.025, 0.25, 5, and 50 mg/kg bw/day) in rats (n = 22 mated/group). One of the aims...... showing that perinatal exposure to BPA can induce increased mammary growth and proliferative lesions in rodents. Our results indicate that low-dose exposure to BPA can affect mammary gland development in male and female rats, although higher doses show a different pattern of effects. The observed...

  1. Unusual anogenital apocrine tumor resembling mammary-like gland adenoma in male perineum: a case report

    Directory of Open Access Journals (Sweden)

    Yoshioka Takako

    2010-06-01

    Full Text Available Abstract A rare case of an apocrine tumor in the male perineal region is reported. A dermal cystic lesion developed in the region between the anus and scrotum of a 74-year-old Japanese male. The cystic lesion, measuring 3.5 × 5.0 cm in size, was lined by columnar or flattened epithelium with occasional apocrine features and supported by a basal myoepithelium lining. A mural nodule, measuring 1 × 1.5 cm in size, protruded into the cystic space and consisted of a solid proliferation of tubular glands with prominent apocrine secretion and basal myoepithelial cells. Immunohistochemical examination showed that the luminal cells were partially positive for gross cystic disease fluid protein 15 and human milk fat globulin 1, and the basal myoepithelial cells were positive for alpha-smooth muscle actin and S-100 protein. Estrogen and progesterone hormone receptors were focally and weakly positive for luminal epithelium. Although no mammary-like glands were present in the dermis around the tumor, this unusual apocrine tumor has been suggested to be derived from male anogenital mammary-like glands and mimic a mammary-like gland adenoma in the male perineum.

  2. Unusual anogenital apocrine tumor resembling mammary-like gland adenoma in male perineum: a case report.

    Science.gov (United States)

    Hatanaka, Kazuhito; Tanimoto, Akihide; Umekita, Yoshihisa; Yoshioka, Takako; Kanekura, Takuro

    2010-06-25

    A rare case of an apocrine tumor in the male perineal region is reported. A dermal cystic lesion developed in the region between the anus and scrotum of a 74-year-old Japanese male. The cystic lesion, measuring 3.5 x 5.0 cm in size, was lined by columnar or flattened epithelium with occasional apocrine features and supported by a basal myoepithelium lining. A mural nodule, measuring 1 x 1.5 cm in size, protruded into the cystic space and consisted of a solid proliferation of tubular glands with prominent apocrine secretion and basal myoepithelial cells. Immunohistochemical examination showed that the luminal cells were partially positive for gross cystic disease fluid protein 15 and human milk fat globulin 1, and the basal myoepithelial cells were positive for alpha-smooth muscle actin and S-100 protein. Estrogen and progesterone hormone receptors were focally and weakly positive for luminal epithelium. Although no mammary-like glands were present in the dermis around the tumor, this unusual apocrine tumor has been suggested to be derived from male anogenital mammary-like glands and mimic a mammary-like gland adenoma in the male perineum.

  3. TBX3 over-expression causes mammary gland hyperplasia and increases mammary stem-like cells in an inducible transgenic mouse model

    Directory of Open Access Journals (Sweden)

    Gulsen Gultekin

    2011-10-01

    Full Text Available Abstract Background The T-box transcription factor TBX3 is necessary for early embryonic development and for the normal development of the mammary gland. Homozygous mutations, in mice, are embryonic lethal while heterozygous mutations result in perturbed mammary gland development. In humans, mutations that result in the haploinsufficiency of TBX3 causes Ulnar Mammary Syndrome (UMS characterized by mammary gland hypoplasia as well as other congenital defects. In addition to its role in mammary gland development, various studies have also supported a role for Tbx3 in breast cancer development. TBX3 is over-expressed in various breast cancer cell lines as well as cancer tissue and has been found to contribute to breast cancer cell migration. Previous studies have suggested that TBX3 contributes to cancer development by its ability to bypass senescence by repressing the expression of p14ARF-tumor suppressor. Although many studies have shown that a dysregulation of TBX3 expression may contribute to cancer progression, no direct evidence shows TBX3 causes breast cancer. Results In this study, we created doxycycline inducible double transgenic mice (MMTV-rtTA;tet-myc-TBX3-IRES-Luciferase to test whether TBX3 over-expression can induce tumor formation within the mammary gland. Although over-expression of TBX3, alone, did not induce tumor formation it did promote accelerated mammary gland development by increasing mammary epithelial cell proliferation. We also show that TBX3 directly binds to and represses NFκBIB, an inhibitor of the NF-κB pathway known to play a role in regulating cell proliferation. Lastly, we also show that the over-expression of TBX3 is associated with an increase in mammary stem-like cells. Conclusions Overall, our data suggests that over-expression of TBX3 may contribute to breast cancer development by promoting accelerated mammary gland development through the inhibition of the NF-κB pathway and stimulation of both mammary

  4. Redefining the expression and function of the inhibitor of differentiation 1 in mammary gland development.

    Directory of Open Access Journals (Sweden)

    Radhika Nair

    2010-08-01

    Full Text Available The accumulation of poorly differentiated cells is a hallmark of breast neoplasia and progression. Thus an understanding of the factors controlling mammary differentiation is critical to a proper understanding of breast tumourigenesis. The Inhibitor of Differentiation 1 (Id1 protein has well documented roles in the control of mammary epithelial differentiation and proliferation in vitro and breast cancer progression in vivo. However, it has not been determined whether Id1 expression is sufficient for the inhibition of mammary epithelial differentiation or the promotion of neoplastic transformation in vivo. We now show that Id1 is not commonly expressed by the luminal mammary epithelia, as previously reported. Generation and analysis of a transgenic mouse model of Id1 overexpression in the mammary gland reveals that Id1 is insufficient for neoplastic progression in virgin animals or to prevent terminal differentiation of the luminal epithelia during pregnancy and lactation. Together, these data demonstrate that there is no luminal cell-autonomous role for Id1 in mammary epithelial cell fate determination, ductal morphogenesis and terminal differentiation.

  5. Analysis of mammary gland according to results of CMT (California Mastitis Test and bacteriological findings in secretion

    Directory of Open Access Journals (Sweden)

    Varatanović Nazif

    2009-01-01

    Full Text Available Health control of the mammary gland was conducted comparing results of CMT (California Mastitis Test and bacteriological findings of milk samples during one year. A total of 3863 secretion samples of mammary glands were collected. There were 85.3% matches for CMT and bacteriological findings. The most frequently isolated causative agents were: staphylococci (52.4%, streptococcus bacteria (23.5%, mixed infections (13.1%, and enterobacteria (10.3%. Secretions disorder and inflammations of mammary gland are most common for the warm period of the year, and very rare for the winter period. With permanent use of these two methods it is possible to obtain satisfactory results in order to get better milk production and health condition of the mammary gland. .

  6. Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland

    Science.gov (United States)

    2014-09-01

    information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information...by daily checking of vaginal plugs, with noon of the day of the plug considered day 0.5. Embryonic stages were confirmed by determining the degree of...LacZ expression underlies a route for axillary cell migration and is an early marker of the mammary mesenchyme We utilized an Ltbp1Llz/+ reporter mouse

  7. Short communication: Differential loss of bovine mammary epithelial barrier integrity in response to lipopolysaccharide and lipoteichoic acid.

    Science.gov (United States)

    Wellnitz, Olga; Zbinden, Christina; Huang, Xiao; Bruckmaier, Rupert M

    2016-06-01

    In the mammary gland, the blood-milk barrier prevents an uncontrolled intermixture of blood and milk constituents and hence maintains the osmotic gradient to draw water into the mammary secretion. During mastitis, the permeability of the blood-milk barrier is increased, which is reflected by the transfer of blood constituents into milk and vice versa. In this study, we aimed to investigate changes in the barrier function of mammary epithelial cells in vitro as induced by cell wall components of different pathogens. Primary bovine mammary epithelial cells from 3 different cows were grown separately on Transwell (Corning Inc., Corning, NY) inserts. The formation of tight junctions between adjacent epithelial cells was shown by transmission electron microscopy and by immunofluorescence staining of the tight junction protein zona occludens-1. The integrity of the epithelial barrier was assayed by means of transepithelial electrical resistance, as well as by diffusion of the fluorophore Lucifer yellow across the cell layer. The release of lactate dehydrogenase (LDH) was used as an indicator for cytotoxic effects. In response to a 24-h challenge with bacterial endotoxin, barrier integrity was reduced after 3 or 7h, respectively, in response to 0.5mg/mL lipopolysaccharide (LPS) from Escherichia coli or 20mg/mL lipoteichoic acid (LTA) from Staphylococcus aureus. No paracellular leakage was observed in response to 0.2mg/mL LPS or 2mg/mL LTA. Although LPS and LTA affected barrier permeability, most likely by opening the tight junctions, only LPS caused cell damage, reflected by increased LDH concentrations in cell culture medium. These results prove a pathogen-specific loss of blood-milk barrier integrity during mastitis, which is characterized by tight junction opening by both LPS and LTA and by additional epithelial cell destruction through LPS. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. Functional analyse of GLUT1 and GLUT12 in glucose uptake in goat mammary gland epithelial cells.

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    Qinghua Yu

    Full Text Available Glucose transport, mediated by glucose transporters, is necessary for mammary gland development and lactation. GLUT1 and GLUT12 could both be expressed in the pregnant and lactating mammary gland to participate in the glucose uptake process. In this study, the goat GLUT1 and GLUT12 genes were cloned from Saanen dairy goats and transfected into goat mammary gland epithelial cells to assess their biological functions and distributions. The results showed that both goat GLUT1 and GLUT12 had 12 predicted membrane-spanning helices. Goat GLUT1 and GLUT12 each influenced the mRNA expression of the other transporter and increased the glucose consumption and lactose yield in GLUT1- and GLUT12-transfected goat mammary gland epithelial cells, respectively. The overexpression of GLUT1 or GLUT12 also increased the expression of amino acid transporters SLC1A5, SLC3A2 and SLC7A5 and affected genes expressions in GMGE cells. Using immunofluorescence staining, GLUT1 was detected throughout the cytoplasm and localized to the Golgi apparatus around the nuclear membrane, whereas GLUT12 was mainly distributed in the perinuclear region and cytoplasm. This study contributes to the understanding of how GLUT1 and GLUT12 cooperate in the incorporation of nutrient uptake into mammary gland epithelial cells and the promotion of milk synthesis in the goat mammary gland during lactation.

  9. Target Gene and Function Prediction of Differentially Expressed MicroRNAs in Lactating Mammary Glands of Dairy Goats

    Directory of Open Access Journals (Sweden)

    Fei Dong

    2013-01-01

    Full Text Available MicroRNAs are small noncoding RNAs that can regulate gene expression, and they can be involved in the regulation of mammary gland development. The differential expression of miRNAs during mammary gland development is expected to provide insight into their roles in regulating the homeostasis of mammary gland tissues. To screen out miRNAs that should have important regulatory function in the development of mammary gland from miRNA expression profiles and to predict their function, in this study, the target genes of differentially expressed miRNAs in the lactating mammary glands of Laoshan dairy goats are predicted, and then the functions of these miRNAs are analyzed via bioinformatics. First, we screen the expression patterns of 25 miRNAs that had shown significant differences during the different lactation stages in the mammary gland. Then, these miRNAs are clustered according to their expression patterns. Computational methods were used to obtain 215 target genes for 22 of these miRNAs. Combining gene ontology annotation, Fisher’s exact test, and KEGG analysis with the target prediction for these miRNAs, the regulatory functions of miRNAs belonging to different clusters are predicted.

  10. Immunohistochemical detection of Mdm2 and p53 in feline mammary gland tumors.

    Science.gov (United States)

    Nakano, Masatoshi; Wu, Haiyan; Taura, Yasuho; Inoue, Makoto

    2006-05-01

    The objective of this study was to evaluate nuclear reactivity of Mdm2 and p53 proteins by immunohistochemical means in feline mammary gland tumors; 12 adenomas which included 6 adenomatous lesions obtained from the tissue adjacent to adenocarcinomas, and 22 adenocarcinomas. Seven adenomas and 18 adenocarcinomas showed moderate or marked Mdm2 reactivity. Sixteen adenocarcinomas showed moderate to marked p53 reactivity, but 9 adenomas showed none. Discordant Mdm2 overexpression was found in 5 adenomas and 3 adenocarcinomas, although co-overexpression of Mdm2 and p53 was found in 15 adenocarcinomas. These results suggest that nuclear overexpression of Mdm2 is present in the tumors of early stage without p53 overexpression and related to feline mammary gland tumorigenesis. Nuclear overexpression of p53 is more frequent in adenocarcinomas, but not in adenomas.

  11. Estrogenic effect of soy isoflavones on mammary gland morphogenesis and gene expression profile

    DEFF Research Database (Denmark)

    Thomsen, Anni R.; Almstrup, Kristian; Nielsen, John E.

    2006-01-01

    We examined the effect of 17 beta-estradiol (E2) and soy isoflavones' exposure on morphogenesis and global gene expression in the murine mammary gland. Three exposure regimens were applied: isoflavones added to the diet throughout either the lactational period (via the dams) or the postweaning...... period and E2 administered orally during the lactational period. Whole mounts of mammary glands were evaluated both in juvenile and adult animals with respect to branching morphogenesis and terminal end bud (TEB) formation. At postnatal day (PND) 28, we observed a significant increase in branching...... morphogenesis in all treated groups with the most pronounced effect after E2 exposure. For the E2-treated animals there was also a significant increase in TEB formation. At PNDs 42-43 the postweaning isoflavone and the E2 groups showed a transient reduction in the number of TEBs. A similar response after...

  12. Macrophages: Regulators of the Inflammatory Microenvironment during Mammary Gland Development and Breast Cancer

    Science.gov (United States)

    Brady, Nicholas J.; Chuntova, Pavlina; Schwertfeger, Kathryn L.

    2016-01-01

    Macrophages are critical mediators of inflammation and important regulators of developmental processes. As a key phagocytic cell type, macrophages evolved as part of the innate immune system to engulf and process cell debris and pathogens. Macrophages produce factors that act directly on their microenvironment and also bridge innate immune responses to the adaptive immune system. Resident macrophages are important for acting as sensors for tissue damage and maintaining tissue homeostasis. It is now well-established that macrophages are an integral component of the breast tumor microenvironment, where they contribute to tumor growth and progression, likely through many of the mechanisms that are utilized during normal wound healing responses. Because macrophages contribute to normal mammary gland development and breast cancer growth and progression, this review will discuss both resident mammary gland macrophages and tumor-associated macrophages with an emphasis on describing how macrophages interact with their surrounding environment during normal development and in the context of cancer. PMID:26884646

  13. Differential expression of type XIV collagen/undulin by human mammary gland intralobular and interlobular fibroblasts.

    Science.gov (United States)

    Atherton, A J; Warburton, M J; O'Hare, M J; Monaghan, P; Schuppan, D; Gusterson, B A

    1998-03-01

    Immunolocalisation of type XIV collagen/undulin in the human mammary gland revealed greater deposition in the interlobular stroma than in the intralobular stroma. The interlobular stroma is located between the breast lobules and their associated intralobular stroma. Fibroblasts isolated from the interlobular stroma synthesised 3- to 5-fold more type XIV collagen/undulin than intralobular fibroblasts, but synthesised type I and type IV collagens in similar amounts. The differential expression of type XIV collagen/undulin was maintained with passage in culture. The results suggest a role for type XIV collagen/undulin in stabilising dense collagen fibrils. The maintenance of two types of structurally distinct stromas may be important during developmental processes in the mammary gland.

  14. PREVENTION OF NIPPLE CRACKS OF THE MAMMARY GLAND IN THE EARLY POSTNATAL PERIOD

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    Marina L. Travina

    2017-01-01

    Full Text Available Preservation and prolongation of the lactation period is not only a guarantee of the child's full physical and mental development but also one of the most important methods for reducing the risk of developing breast cancer. Problems with the mammary gland nipple in a woman in the early postnatal period lead to a refusal of lactation. We carried out a retrospective analysis (period from 2010 to 2016 of the causes of traumatizing mammary gland nipples in the early postnatal period in 172 women (mean age 29.1 ± 4.3 years. Methods of prevention and treatment of nipple injuries in the early postnatal period have been offered for the lactation period prolongation.

  15. Identification of prognostic collagen signatures and potential therapeutic stromal targets in canine mammary gland carcinoma.

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    Ashley Case

    Full Text Available Increasing evidence indicates that the tumor microenvironment plays a critical role in regulating the biologic behavior of breast cancer. In veterinary oncology, there is a need for improved prognostic markers to accurately identify dogs at risk for local and distant (metastatic recurrence of mammary gland carcinoma and therefore would benefit from adjuvant therapy. Collagen density and fiber organization have been shown to regulate tumor progression in both mouse and human mammary tumors, with certain collagen signatures predicting poor outcomes in women with breast cancer. We hypothesized that collagen signatures in canine mammary tumor biopsies can serve as prognostic biomarkers and potential targets for treatment. We used second harmonic generation imaging to evaluate fibrillar collagen density, the presence of a tumor-stromal boundary, tumor associated collagen signatures (TACS and individual collagen fiber characteristics (width, length and straightness in grade I/II and grade III canine mammary tumors. Collagen density, as well as fiber width, length and straightness, were inversely correlated with patient overall survival time. Notably, grade III cases were less likely to have a tumor-stromal boundary and the lack of a boundary predicted poor outcome. Importantly, a lack of a defined tumor-stromal boundary and an increased collagen fiber width were associated with decreased survival even when tumor grade, patient stage, ovariohysterectomy status at the time of mammary tumor excision, and histologic evidence of lymphovascular invasion were considered in a multivariable model, indicating that these parameters could augment current methods to identify patients at high risk for local or metastatic progression/recurrence. Furthermore, these data, which identify for the first time, prognostic collagen biomarkers in naturally occurring mammary gland neoplasia in the dog, support the use of the dog as a translational model for tumor

  16. Mammary Gland Cell Culture of Macaca fascicularis as a Reservoir for Stem Cells

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    Silmi Mariya

    2017-07-01

    Full Text Available The mammary gland contains adult stem cells that are capable of self-renewal and are likely target for neoplastic transformation leading to breast cancer. In this study, we developed a cell culture derived from the mammary glands of cynomolgus monkeys (Macaca fascicularis (MfMC and furthermore identified the expression of markers for stemness and estrogen receptor-associated activities. We found that the primary culture can be successfully subcultured to at least 3 passages, primarily epithelial-like in morphology, the cultured cells remained heterogenous in phenotype as they expressed epithelial cell markers CD24, CK18, and marker for fibroblast S1004A. Importantly, the cell population also consistently expressed the markers of mammary stem cells (ITGB1 or CD29 and ITGA6 or CD49f, mesenchymal stem cells (CD73 and CD105 and pluripotency (NANOG, OCT4, SOX2. In addition to this, the cells were also positive for Estrogen Receptor (ER, and ER-activated marker Trefoil Factor 1, suggesting an estrogen responsiveness of the culture model. These results indicate that our cell culture model is a reliable model for acquiring a population of cells with mammary stem cell properties and that these cultures may also serve as a reservoir from which more purified populations of stem cell populations can be isolated in the future.

  17. Stat5a is mandatory for adult mammary gland development and lactogenesis.

    Science.gov (United States)

    Liu, X; Robinson, G W; Wagner, K U; Garrett, L; Wynshaw-Boris, A; Hennighausen, L

    1997-01-15

    Prolactin (PRL) induces mammary gland development (defined as mammopoiesis) and lactogenesis. Binding of PRL to its receptor leads to the phosphorylation and activation of STAT (signal transducers and activators of transcription) proteins, which in turn promote the expression of specific genes. The activity pattern of two STAT proteins, Stat5a and Stat5b, in mammary tissue during pregnancy suggests an active role for these transcription factors in epithelial cell differentiation and milk protein gene expression. To investigate the function of Stat5a in mammopoiesis and lactogenesis we disrupted this gene in mice by gene targeting. Stat5a-deficient mice developed normally and were indistinguishable from hemizygous and wild-type littermates in size, weight, and fertility. However, mammary lobuloalveolar outgrowth during pregnancy was curtailed, and females failed to lactate after parturition because of a failure of terminal differentiation. Although Stat5b has a 96% similarity with Stat5a and a superimposable expression pattern during mammary gland development it failed to counterbalance for the absence of Stat5a. These results document that Stat5a is the principal and an obligate mediator of mammopoietic and lactogenic signaling.

  18. Relationship between growth of nursing pigs and composition of sow colostrum and milk from anterior and posterior mammary glands

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    Šamanc H.

    2013-01-01

    Full Text Available Piglets that nurse anterior mammary glands grow faster than those suckling posterior mammary glands. The underlying mechanisms are not known. The purpose of this study was to investigate if there is a difference in composition in colostrum and milk secreted by anterior and posterior mammary glands. Seven healthy sows were used. The first three pairs of mammary glands were defined as anterior mammary glands (AMG and the rest as posterior mammary glands (PMG. Additionally, the total of 87 born piglets from 7 litters derived from the sows involved in the experiment was analyzed. Piglets from each litter that nursed AMG were defined as AMG group while the rest of piglets from the litter were defined as PMG group. Colostrum and milk were collected at days 1, 2, 3 and 7 after parturition. Samples taken from anterior and posterior mammary glands were pooled, respectively. Results showed that total protein, IGF-I and insulin concentrations were significantly higher in the colostrum of anterior than posterior glands and IGF-I concentration remained significantly higher in milk of anterior compared to posterior glands. There were no significant differences in fat, dry matter and lactose among anterior and posterior glands during all examined periods. Additionally, blood samples from nursing sows were obtained at days 1 and 7 after parturition. Results showed that concentrations of Ca, glucose, total protein, albumin, globulin, total bilirubin and insulin significantly increased from day 1 to day 7 of parturition while concentrations of P, BUN, CK and IGF-I did not significantly change during this period. Initial body weight of pigs nursing the anterior gland was higher but not significantly that those suckling posterior glands. Pigs that nursed anterior glands gained weight faster then those which suckled posterior glands resulting with significantly higher body weigh of piglets nursing anterior compared to posterior glands at day 8 of neonatal life (p

  19. A tool for the quantitative spatial analysis of mammary gland epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Ortiz de Solorzano, Carlos; Fernandez-Gonzalez, Rodrigo

    2004-04-09

    In this paper we present a method for the spatial analysis of complex cellular systems based on a multiscale study of neighborhood relationships. A function to measure those relationships, M, is introduced. The refined Relative Neighborhood Graph is then presented as a method to establish vicinity relationships within layered cellular structures, and particularized to epithelial cell nuclei in the mammary gland. Finally, the method is illustrated with two examples that show interactions within one population of epithelial cells and between two different populations.

  20. The myoepithelial cell: its role in normal mammary glands and breast cancer.

    Science.gov (United States)

    Sopel, M

    2010-02-01

    Mammary gland epithelium is composed of an inner layer of secretory cells (luminal) and an outer layer of myoepithelial cells (MEC) bordering the basal lamina which separates the epithelial layer from the extracellular matrix. Mature MECs morphologically resemble smooth muscle cells; however, they exhibit features typical for epithelial cells, such as the presence of specific cytokeratin filaments. During lactation, secretory cells synthesize milk components, which are collected in alveoli and duct lumen, and transported to the nipple as a result of MEC contraction. Although the induction of MEC contraction results from oxytocin action, also other, still unknown auto/paracrine mechanisms participate in the regulation of this process. As well as milk ejection, MECs are involved in mammary gland morphogenesis in all developmental stages, modulating proliferation and differentiation of luminal cells. They take part in the formation of extracellular matrix, synthesizing its components and secreting proteinases and their inhibitors. In addition, MECs are regarded as natural cancer suppressors, stabilizing the normal structure of the mammary gland, they secrete suppressor proteins (e.g. maspin) limiting cancer growth, invasiveness, and neoangiogenesis. The majority of malignant breast cancers are derived from luminal cells, whereas neoplasms of MEC origin are the most seldom and usually benign form of breast tumours. MECs are markedly resistant to malignant transformation and they are able to suppress the transformation of neighboring luminal cells. Therefore, a deeper insight into the role of MECs in the physiology and pathology of mammary glands would allow a better understanding of cancerogenesis mechanisms and possible application of specific MEC markers in the diagnosis and therapy of breast cancer.

  1. Twisted Gastrulation as a BMP Modulator during Mammary Gland Development and Tumorigenesis

    Science.gov (United States)

    2014-05-01

    Humoral bone morphogenetic protein 2 is sufficient for inducing breast cancer microcalcification . Mol Imaging. 2008; 7:175–86. [PubMed: 19123988...Twsg1 is expressed in mammary glands from wild type (WT) mice at 3, 6 and 8 weeks of life, and is differentially expressed in breast cancer , yet its...role in MG development and breast cancer pathogenesis is unknown. This study is designed to determine how TWSG1 regulates the invasion of normal MG

  2. Milk ceruloplasmin and its expression by mammary gland and liver in pigs.

    Science.gov (United States)

    Cerveza, P J; Mehrbod, F; Cotton, S J; Lomeli, N; Linder, M C; Fonda, E G; Wickler, S J

    2000-01-15

    Concentrations of ceruloplasmin and copper in milk and blood plasma, the nature of milk ceruloplasmin, and the effects of lactation and gestation on these parameters, as well as the expression of ceruloplasmin mRNA by the mammary gland, were examined in pigs. As seen previously in humans, ceruloplasmin and copper concentrations in sow milk were much higher a few days after birth than 1 month later, averaging 26.5 and 6.6 mg ceruloplasmin/L (by immunoassay) and 1.67 and 0.34 mg total Cu/L, on days 3 and 33 postpartum, respectively. Values for ceruloplasmin oxidase activity (measured with p-phenylene diamine) were 7.8 and 1.3 nmol/min/L, respectively. Daily milk ceruloplasmin production went from 61 to 22 mg/day and daily copper output from 38 to 12 mg/day. In contrast, there was little or no variation in serum ceruloplasmin concentration during lactation or gestation, although total plasma copper was high at the end of gestation. Milk ceruloplasmin was of the same apparent size as serum ceruloplasmin, as determined by SDS-PAGE and immunoblotting, and ceruloplasmin mRNAs of liver and mammary gland were indistinguishable by Northern analysis and RT-PCR of the various exons. Expression of total RNA and ceruloplasmin mRNA, as detected in biopsies of mammary gland, increased markedly upon onset of lactation and then declined during the next month in conjunction with a drop in milk ceruloplasmin production. The results indicate that milk ceruloplasmin, while being the same protein as in plasma, is not derived from the plasma but is produced by the mammary gland. Copyright 2000 Academic Press.

  3. Microbial agents in macroscopically healthy mammary gland tissues of small ruminants

    OpenAIRE

    Liliana Spuria; Elena Biasibetti; Donal Bisanzio; Ilaria Biasato; Daniele De Meneghi; Patrizia Nebbia; Patrizia Robino; Paolo Bianco; Michele Lamberti; Claudio Caruso; Alessia Di Blasio; Simone Peletto; Loretta Masoero; Alessandro Dondo; Maria Teresa Capucchio

    2017-01-01

    Background Health of mammary glands is fundamental for milk and dairy products hygiene and quality, with huge impacts on consumers welfare. Methods This study aims to investigate the microbial agents (bacteria, fungi and lentiviruses) isolated from 89 macroscopically healthy udders of regularly slaughtered small ruminants (41 sheep, 48 goats), also correlating their presence with the histological findings. Multinomial logistic regression was applied to evaluate the association between lesions...

  4. Deciphering Transcriptome and Complex Alternative Splicing Transcripts in Mammary Gland Tissues from Cows Naturally Infected with Staphylococcus aureus Mastitis

    Science.gov (United States)

    Jiang, Qiang; Yang, Chun Hong; Zhang, Yan; Sun, Yan; Li, Rong Ling; Wang, Chang Fa; Zhong, Ji Feng; Huang, Jin Ming

    2016-01-01

    Alternative splicing (AS) contributes to the complexity of the mammalian proteome and plays an important role in diseases, including infectious diseases. The differential AS patterns of these transcript sequences between the healthy (HS3A) and mastitic (HS8A) cows naturally infected by Staphylococcus aureus were compared to understand the molecular mechanisms underlying mastitis resistance and susceptibility. In this study, using the Illumina paired-end RNA sequencing method, 1352 differentially expressed genes (DEGs) with higher than twofold changes were found in the HS3A and HS8A mammary gland tissues. Gene ontology and KEGG pathway analyses revealed that the cytokine–cytokine receptor interaction pathway is the most significantly enriched pathway. Approximately 16k annotated unigenes were respectively identified in two libraries, based on the bovine Bos taurus UMD3.1 sequence assembly and search. A total of 52.62% and 51.24% annotated unigenes were alternatively spliced in term of exon skipping, intron retention, alternative 5′ splicing and alternative 3ʹ splicing. Additionally, 1,317 AS unigenes were HS3A-specific, whereas 1,093 AS unigenes were HS8A-specific. Some immune-related genes, such as ITGB6, MYD88, ADA, ACKR1, and TNFRSF1B, and their potential relationships with mastitis were highlighted. From Chromosome 2, 4, 6, 7, 10, 13, 14, 17, and 20, 3.66% (HS3A) and 5.4% (HS8A) novel transcripts, which harbor known quantitative trait locus associated with clinical mastitis, were identified. Many DEGs in the healthy and mastitic mammary glands are involved in immune, defense, and inflammation responses. These DEGs, which exhibit diverse and specific splicing patterns and events, can endow dairy cattle with the potential complex genetic resistance against mastitis. PMID:27459697

  5. Two distinct phases of apoptosis in mammary gland involution: proteinase-independent and -dependent pathways

    Energy Technology Data Exchange (ETDEWEB)

    Lund, Leif R; Romer, John; Thomasset, Nicole; Solberg, Helene; Pyke, Charles; Bissell, Mina J; Dano, Keld; Werb, Zena

    1996-01-01

    Postlactational involution of the mammary gland is characterized by two distinct physiological events: apoptosis of the secretory, epithelial cells undergoing programmed cell death, and proteolytic degradation of the mammary gland basement membrane. We examined the spatial and temporal patterns of apoptotic cells in relation to those of proteinases during involution of the BALB/c mouse mammary gland. Apoptosis was almost absent during lactation but became evident at day 2 of involution, when {beta}-casein gene expression was still high. Apoptotic cells were then seen at least up to day 8 of involution, when {beta}-casein gene expression was being extinguished. Expression of sulfated glycoprotein-2 (SGP-2), interleukin-1{beta} converting enzyme (ICE) and tissue inhibitor of metalloproteinases-1 was upregulated at day 2, when apoptotic cells were seen initially. Expression of the matrix metalloproteinases gelatinase A and stromelysin-1 and the serine proteinase urokinase-type plasminogen activator, which was low during lactation, was strongly upregulated in parallel starting at day 4 after weaning, coinciding with start of the collapse of the lobulo-alveolar structures and the intensive tissue remodeling in involution. The major sites of mRNA synthesis for these proteinases were fibroblast-like cells in the periductal stroma and stromal cells surrounding the collapsed alveoli, suggesting that the degradative phase of involution is due to a specialized mesenchymal-epithelial interaction. To elucidate the functional role of these proteinases during involution, at the onset of weaning we treated mice systemically with the glucocorticoid hydrocortisone, which is known to inhibit mammary gland involution. Although the initial wave of apoptotic cells appeared in the lumina of the gland, the dramatic regression and tissue remodeling usually evident by day 5 was substantially inhibited by systemic treatment with hydrocortisone. mRNA and protein for gelatinase A, stromelysin

  6. Two distinct phases of apoptosis in mammary gland involution: proteinase-independent and -dependent pathways.

    Science.gov (United States)

    Lund, L R; Rømer, J; Thomasset, N; Solberg, H; Pyke, C; Bissell, M J; Danø, K; Werb, Z

    1996-01-01

    Postlactational involution of the mammary gland is characterized by two distinct physiological events: apoptosis of the secretory, epithelial cells undergoing programmed cell death, and proteolytic degradation of the mammary gland basement membrane. We examined the spatial and temporal patterns of apoptotic cells in relation to those of proteinases during involution of the BALB/c mouse mammary gland. Apoptosis was almost absent during lactation but became evident at day 2 of involution, when beta-casein gene expression was still high. Apoptotic cells were then seen at least up to day 8 of involution, when beta-casein gene expression was being extinguished. Expression of sulfated glycoprotein-2 (SGP-2), interleukin-1 beta converting enzyme (ICE) and tissue inhibitor of metalloproteinases-1 was upregulated at day 2, when apoptotic cells were seen initially. Expression of the matrix metalloproteinases gelatinase A and stromelysin-1 and the serine proteinase urokinase-type plasminogen activator, which was low during lactation, was strongly upregulated in parallel starting at day 4 after weaning, coinciding with start of the collapse of the lobulo-alveolar structures and the intensive tissue remodeling in involution. The major sites of mRNA synthesis for these proteinases were fibroblast-like cells in the periductal stroma and stromal cells surrounding the collapsed alveoli, suggesting that the degradative phase of involution is due to a specialized mesenchymal-epithelial interaction. To elucidate the functional role of these proteinases during involution, at the onset of weaning we treated mice systemically with the glucocorticoid hydrocortisone, which is known to inhibit mammary gland involution. Although the initial wave of apoptotic cells appeared in the lumina of the gland, the dramatic regression and tissue remodeling usually evident by day 5 was substantially inhibited by systemic treatment with hydrocortisone. mRNA and protein for gelatinase A, stromelysin-1 and

  7. Detection of expressional changes induced by intrauterine growth restriction in the developing rat mammary gland via exploratory pathways analysis.

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    Lea Beinder

    Full Text Available Intrauterine growth restriction (IUGR is thought to lead to fetal programming that in turn contributes to developmental changes of many organs postnatally. There is evidence that IUGR is a risk factor for the development of metabolic and cardiovascular disease later in life. A higher incidence of breast cancer was also observed after IUGR. This could be due to changes in mammary gland developmental pathways. We sought to characterise IUGR-induced alterations of the complex pathways of mammary development at the level of the transcriptome in a rat model of IUGR, using pathways analysis bioinformatics.We analysed the mammary glands of Wistar rats with IUGR induced by maternal low protein (LP diet at the beginning (d21 and the end (d28 of pubertal ductal morphogenesis. Mammary glands of the LP group were smaller in size at d28, however did not show morphologic changes. We identified multiple differentially expressed genes in the mammary gland using Agilent SurePrint arrays at d21 and d28. In silico analysis was carried out using Ingenuity Pathways Analysis. In mammary gland tissue of LP rats at d21 of life a prominent upregulation of WT1 and CDKN1A (p21 expression was observed. Differentially regulated genes were associated with the extracellular regulated kinase (ERK-1/-2 pathway. Western Blot analysis showed reduced levels of phosphorylated ERK-1/-2 in the mammary glands of the LP group at d21. To identify possible changes in circulating steroid levels, serum LC-Tandem mass-spectrometry was performed. LP rats showed higher serum progesterone levels and an increased corticosterone/dehydrocorticosterone-ratio at d28.Our data obtained from gene array analysis support the hypothesis that IUGR influences pubertal development of the rat mammary gland. We identified prominent differential regulation of genes and pathways for factors regulating cell cycle and growth. Moreover, we detected new pathways which appear to be programmed by IUGR.

  8. Non-Invasive Assessment of Sentinel Lymph Nodes That Drain the Tumoral Mammary Glands in Female Dog

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    Florin Gheorghe Stan

    2016-11-01

    Full Text Available Introduction: Mammary gland tumours occupy a significant place in the pathology of this species. Female dogs that are not spayed after their first heat cycle have a higher predisposition of developing mammary tumours. Most tumours metastasize at distance via the lymphatic system. In these conditions, the sentinel lymph nodes of the mammary glands must be assessed prior to surgical treatment. Aims: Considering the insufficient usage of non-invasive investigative methods of the sentinel lymph nodes, the aim of this study is to describe the sonographic anatomy of the lymph nodes that drain the mammary gland tumours in female dog. Materials and Methods: Twelve dog females presenting tumours of the cranial and caudal abdominal mammary glands (A1 and A2, inguinal mammary gland (I and cranial thoracic mammary gland (T1 were examined (group I. In addition, a control group composed of eight dog females was used (group II. The axillary and superficial inguinal lymph nodes were evaluated using an algorithm composed of gray-scale ultrasound, Doppler technique, contrast enhanced ultrasound (CEUS and real time elastography. Surgical excision of the sentinel lymph nodes was performed and samples for histopathological examination were taken. Results: The following ultrasonographic findings revealed on gray-scale examination were suspected for the metastatic infiltration: hypoechoic pattern, round shape, hillus absence and heterogenicity. Doppler technique showed an aberrant and mixed vascularisation of the lymph nodes, while the CEUS revealed incomplete enhancement of lymph nodes parenchyma. On real time elastography, the presence of blue areas in more than 50% from the lymph nodes parenchyma led us to conclude that the lymph node stiffness was caused by metastatic infiltration. Histopathological examination confirmed the presence of the metastatic infiltration in 97% of the examined lymph nodes. Conclusion: The algorithm composed of gray-scale ultrasound

  9. Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland.

    Science.gov (United States)

    Johnson, Michael D; Kenney, Nicholas; Stoica, Adriana; Hilakivi-Clarke, Leena; Singh, Baljit; Chepko, Gloria; Clarke, Robert; Sholler, Peter F; Lirio, Apolonio A; Foss, Colby; Reiter, Ronald; Trock, Bruce; Paik, Soonmyoung; Martin, Mary Beth

    2003-08-01

    It has been suggested that environmental contaminants that mimic the effects of estrogen contribute to disruption of the reproductive systems of animals in the wild, and to the high incidence of hormone-related cancers and diseases in Western populations. Previous studies have shown that functionally, cadmium acts like steroidal estrogens in breast cancer cells as a result of its ability to form a high-affinity complex with the hormone binding domain of the estrogen receptor. The results of the present study show that cadmium also has potent estrogen-like activity in vivo. Exposure to cadmium increased uterine wet weight, promoted growth and development of the mammary glands and induced hormone-regulated genes in ovariectomized animals. In the uterus, the increase in wet weight was accompanied by proliferation of the endometrium and induction of progesterone receptor (PgR) and complement component C3. In the mammary gland, cadmium promoted an increase in the formation of side branches and alveolar buds and the induction of casein, whey acidic protein, PgR and C3. In utero exposure to the metal also mimicked the effects of estrogens. Female offspring experienced an earlier onset of puberty and an increase in the epithelial area and the number of terminal end buds in the mammary gland.

  10. Staphylococcus aureus effect of different factors on mammary gland infection with staphylococcus aureus bacteria

    Directory of Open Access Journals (Sweden)

    Jurčevič Alen

    2004-01-01

    Full Text Available The objective of our investigation was to determine how certain factors (the environment, treatment, prevention, animal affect udder infection with Staphylococcus aureurs (S. aureus bacteria. A questionnaire investigated the effect of different factors on the frequency of infection with S. aureus bacteria. We established that prevention, treatment on the basis of results of bacteriological examinations and antibiograms, and the elimination of the negative influence of the environment, form a basis for reducing the frequency of udder infections. We verified the questionannire results with the variant analysis method and established that the effect of the environment significantly digresses from the other factors (prevention treatment and diagnosis, animal. Our results show that the breeder, with good prevention and good treatment of mastitis, often disregards the effects of the barn and the environment in which the cows are maintained. Poor barn conditions have a negative effect on cow resistance and at the same time enable the existence and multiplication of pathogenic species of bacteria. In addition to the maintenance conditions, one must not forget prevention and therapy of mammary gland inflammation, either. On the grounds of our previous investigations (Pengov et al., 2000, we recommend for the therapy of mammary gland inflammation the use of a combination of amoxicillin and clavulonic acid, and as prevention of mammary gland inflammation the use of an udder ointment.

  11. Cyclopedic protein expression analysis of cultured canine mammary gland adenocarcinoma cells from six tumours.

    Science.gov (United States)

    Nakagawa, T; Watanabe, M; Ohashi, E; Uyama, R; Takauji, S; Mochizuki, M; Nishimura, R; Ogawa, H; Sugano, S; Sasaki, N

    2006-06-01

    We characterised cultured canine mammary gland adenocarcinoma cells by exhaustive step protein expression analysis to identify factors associated with tumour progression or metastasis of canine mammary gland tumour. Cultured adenocarcinoma cells derived from a total of 3 primary and 3 metastatic lesions from 3 dogs (CHMp/m, CIPp/m and CNMp/m, where CHM, CIP, and CNM indicate the 3 animals) were used in this study. The expression of 24 proteins reported to be related to tumourigenesis or malignancy of human breast cancers were examined by Western blot analysis using 24 antibodies. The expression of sialyl Lewis X [sLe(x)] was only observed in CHMm cells, which were derived from pleural effusion. This expression was further confirmed by immunohistochemistry. The levels of some factors, such as 14-3-3sigma, cyclinD1 and Rb, differed among cells or between the primary and metastatic cells in the pair. Though the difference in their expression was not consistent within the cells from primary and metastatic origin, this characterisation should provide useful information for further molecular analysis of these cultured cells. Since some of the factors, such as sLe(x), 14-3-3sigma, cyclinD1 and Rb, showed different levels of expression in the pair, these cultured cells might be meaningful tools for clarification of distant metastasis in canine mammary gland tumours.

  12. Mammary gland lactose, plasma progesterone and lactogenesis in the marsupial Macropus eugenii.

    Science.gov (United States)

    Findlay, L; Ward, K L; Renfree, M B

    1983-06-01

    Mammary gland lactose concentrations in pregnant tammar wallabies remained low at 115 +/- 24 (S.E.M.) micrograms/g wet weight of tissue until immediately before parturition, then increased to 1274 +/- 262 micrograms/g after birth. Concentrations in non-pregnant cyclic animals were generally low (143 +/- 36 micrograms/g), but were raised in three animals around the time of oestrus. Removal of the corpus luteum on day 18 of pregnancy or the oestrous cycle caused an increase in lactose concentrations in both lutectomized and sham-operated animals. This occurred despite a significant lowering of peripheral plasma progesterone concentration in only the lutectomized group. Plasma cortisol concentrations were high in some of these animals, but showed no consistent relationships with the raised lactose concentrations. The increased peripartum lactose concentration normally coincides with a sharp fall in peripheral plasma progesterone concentration, but artificial maintenance of high progesterone levels had no effect on the increase of mammary gland lactose at parturition. Mammary gland lactose concentrations in tammar wallabies are therefore a useful indicator of biosynthetic activity and as an index of lactogenesis but the role, if any, of progesterone withdrawal in lactogenesis remains unclear.

  13. Clear Cell Sarcoma of the Neck Which Metastasized to the Mammary Gland

    Directory of Open Access Journals (Sweden)

    Ippei Fukada

    2013-01-01

    Full Text Available Malignant neoplasms very rarely metastasize to the mammary gland, the incidence of which is reported as 0.5–2%. Clear cell sarcoma is a rare neoplasm, accounting for approximately 1% of all soft tissue tumors, which commonly occurs in the distal extremities of young adults aged approximately 20 to 40 years. So it is also called malignant melanoma of soft parts because it frequently produces melanin. We report a case of a 26-year-old woman who presented with a neck mass. The mass was surgically removed, and pathological diagnosis was clear cell sarcoma of the neck, harboring the EWS-ATF1 chimeric gene. Computed tomography detected a right breast mass 11 months after operation. She was referred to our department, and the right breast tumor was resected. Histopathological examination revealed a 2.5-cm, well-defined mass composed of nests of small, spindle-shaped tumor cells with abundant, clear cytoplasm containing round nuclei and prominent nucleoli. The tumor cells were immunohistochemically positive for HMB45, S-100, and Melan-A. These findings led to a diagnosis of metastasis of clear cell sarcoma to the mammary gland. This is the first report of clear cell sarcoma of the neck which metastasized to the mammary gland.

  14. Regulation of fluid flow through the mammary gland of dairy cows and its effect on milk production: a systematic review.

    Science.gov (United States)

    Cai, Jie; Wang, Diming; Liu, Jianxin

    2017-07-31

    Dairy milk consists of more than 85% water. Therefore, understanding the regulation of fluid absorption in the mammary gland is relevant to improving milk production. In recent decades, studies using different approaches, including blood flow, transmembrane fluid flow, tight junction, fluid flow of the paracellular pathway and functional mammary epithelial cell state, have been conducted aiming to investigate how mammary gland fluid absorption is regulated. However, the relationship between regulation mechanisms of fluid flow and milk production has not been studied systematically. The present review summarizes a series of key milk yield regulatory factors mediated by whole-mammary fluid flow, including milk, mammary blood flow, blood/tissue fluid-cell fluid flow and cell-alveolus fluid flow. Whole-mammary fluid flow regulates milk production by altering transporter activity, ion channels, local microcirculation-related factors, driving force of fluid transport (osmotic pressure or electrochemical gradient), cellular connection state and a cell volume sensitive mechanism. In addition, whole-mammary fluid flow plays important roles in milk synthesis and secretion. Knowledge gained from fluid flow-mediated regulatory mechanisms of the dairy mammary gland will lead to a fundamental understanding of lactation biology and will be beneficial for the improvement of dairy productivity. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  15. Influence of prevastein (R), an isoflavone-rich soy product, on mammary gland development and Tumorigenesis in Tg.NK (MMTV/c-neu) mice

    DEFF Research Database (Denmark)

    Thomsen, Anni R.; Mortensen, Alicja; Breinholt, Vibeke

    2005-01-01

    We investigated spontaneous mammary tumor development and mammary gland morphogenesis in female Tg.NK mice postnatally exposed to dietary soy isoflavones (0, 11, 39, and 130 mg aglycones/kg diet) added to a Western-style diet. Instead of preventing mammary tumorigenesis, the highest dose of isofl......We investigated spontaneous mammary tumor development and mammary gland morphogenesis in female Tg.NK mice postnatally exposed to dietary soy isoflavones (0, 11, 39, and 130 mg aglycones/kg diet) added to a Western-style diet. Instead of preventing mammary tumorigenesis, the highest dose...

  16. CCL2-driven inflammation increases mammary gland stromal density and cancer susceptibility in a transgenic mouse model.

    Science.gov (United States)

    Sun, Xuan; Glynn, Danielle J; Hodson, Leigh J; Huo, Cecilia; Britt, Kara; Thompson, Erik W; Woolford, Lucy; Evdokiou, Andreas; Pollard, Jeffrey W; Robertson, Sarah A; Ingman, Wendy V

    2017-01-11

    Macrophages play diverse roles in mammary gland development and breast cancer. CC-chemokine ligand 2 (CCL2) is an inflammatory cytokine that recruits macrophages to sites of injury. Although CCL2 has been detected in human and mouse mammary epithelium, its role in regulating mammary gland development and cancer risk has not been explored. Transgenic mice were generated wherein CCL2 is driven by the mammary epithelial cell-specific mouse mammary tumour virus 206 (MMTV) promoter. Estrous cycles were tracked in adult transgenic and non-transgenic FVB mice, and mammary glands collected at the four different stages of the cycle. Dissected mammary glands were assessed for cyclical morphological changes, proliferation and apoptosis of epithelium, macrophage abundance and collagen deposition, and mRNA encoding matrix remodelling enzymes. Another cohort of control and transgenic mice received carcinogen 7,12-Dimethylbenz(a)anthracene (DMBA) and tumour development was monitored weekly. CCL2 protein was also quantified in paired samples of human breast tissue with high and low mammographic density. Overexpression of CCL2 in the mammary epithelium resulted in an increased number of macrophages, increased density of stroma and collagen and elevated mRNA encoding matrix remodelling enzymes lysyl oxidase (LOX) and tissue inhibitor of matrix metalloproteinases (TIMP)3 compared to non-transgenic controls. Transgenic mice also exhibited increased susceptibility to development of DMBA-induced mammary tumours. In a paired sample cohort of human breast tissue, abundance of epithelial-cell-associated CCL2 was higher in breast tissue of high mammographic density compared to tissue of low mammographic density. Constitutive expression of CCL2 by the mouse mammary epithelium induces a state of low level chronic inflammation that increases stromal density and elevates cancer risk. We propose that CCL2-driven inflammation contributes to the increased risk of breast cancer observed in women

  17. Mammary gland morphology in Sprague-Dawley rats following treatment with an organochlorine mixture in utero and neonatal genistein.

    Science.gov (United States)

    Foster, Warren G; Younglai, Edward V; Boutross-Tadross, Odette; Hughes, Claude L; Wade, Michael G

    2004-01-01

    In a related reproductive toxicology study designed to investigate the effects of in utero exposure to environmental toxicants and potential interaction with postnatal genistein, gross enlargement of thoracic mammary glands was observed in female offspring at 200 days of age. Therefore, the objective of this study was to analyze the effect of in utero exposure to a mixture of toxicants on mammary gland morphology. Time-mated Sprague-Dawley rats were treated on days 9-16 of gestation with vehicle or a mixture of environmental toxicants at 1x the acceptable daily intake. Furthermore, it is unclear whether postnatal exposure to phytoestrogens in soy formulas poses breast cancer benefit or risk, and potential interactions with environmental toxicants are unknown. Therefore, half the female pups from each treatment group received either subcutaneous vehicle or genistein (10 microg/g body weight [bw]/day) on postnatal days 2-8. Following necropsy at 200 days of age, a pathologist, blinded to treatment groups, examined mammary gland histopathology. Only mild histological changes were found in mammary glands of rats exposed to the mixture in utero while pronounced ductal hyperplasia, lactational changes, and fibrosis were observed in mammary glands from the genistein group and were more prominent in the mixture + genistein group. Mammary glands of the control group were histologically normal. Collectively, our results reveal that postnatal exposure to pharmacological levels of genistein induces profound morphological changes in the mammary glands of adult female rats, and that high levels of phytoestrogens possess the potential to modulate the toxicological effects of toxicant mixtures.

  18. Paracrine interactions between primary human macrophages and human fibroblasts enhance murine mammary gland humanization in vivo.

    Science.gov (United States)

    Fleming, Jodie M; Miller, Tyler C; Kidacki, Michal; Ginsburg, Erika; Stuelten, Christina H; Stewart, Delisha A; Troester, Melissa A; Vonderhaar, Barbara K

    2012-06-25

    Macrophages comprise an essential component of the mammary microenvironment necessary for normal gland development. However, there is no viable in vivo model to study their role in normal human breast function. We hypothesized that adding primary human macrophages to the murine mammary gland would enhance and provide a novel approach to examine immune-stromal cell interactions during the humanization process. Primary human macrophages, in the presence or absence of ectopic estrogen stimulation, were used to humanize mouse mammary glands. Mechanisms of enhanced humanization were identified by cytokine/chemokine ELISAs, zymography, western analysis, invasion and proliferation assays; results were confirmed with immunohistological analysis. The combined treatment of macrophages and estrogen stimulation significantly enhanced the percentage of the total gland humanized and the engraftment/outgrowth success rate. Timecourse analysis revealed the disappearance of the human macrophages by two weeks post-injection, suggesting that the improved overall growth and invasiveness of the fibroblasts provided a larger stromal bed for epithelial cell proliferation and structure formation. Confirming their promotion of fibroblasts humanization, estrogen-stimulated macrophages significantly enhanced fibroblast proliferation and invasion in vitro, as well as significantly increased proliferating cell nuclear antigen (PCNA) positive cells in humanized glands. Cytokine/chemokine ELISAs, zymography and western analyses identified TNFα and MMP9 as potential mechanisms by which estrogen-stimulated macrophages enhanced humanization. Specific inhibitors to TNFα and MMP9 validated the effects of these molecules on fibroblast behavior in vitro, as well as by immunohistochemical analysis of humanized glands for human-specific MMP9 expression. Lastly, glands humanized with macrophages had enhanced engraftment and tumor growth compared to glands humanized with fibroblasts alone. Herein, we

  19. Mammary Analogue Secretory Carcinoma (MASC) of salivary gland in four Mexican patients

    Science.gov (United States)

    Mosqueda-Taylor, Adalberto; Domínguez-Malagón, Hugo; Michal, Michal

    2015-01-01

    The Clinco-pathological, immunohistochemical and molecular findings of four cases of Mammary Analogue Secretory Carcinoma (MASC) of salivary glands found in Mexico are described. The cases were extracted from 253 salivary gland tumors from a single institution in Mexico City. The 85 candidates for initial selection were: low grade mucoepidermoid carcinoma (MEC) (N=70 ), acinic cell cancinoma (AciCC) (N=14), papillary cystadenocarcinoma (N=1), and adenocarcinoma NOS (N=0). Tumors with some histological features consistent with MASC (N= 17, 6.7%) were studied by immunohistochemistry for mammaglobin, STAT5, and S-100 protein and four cases were positive (1.5%), thus the diagnosis of MASC was established, and these were submitted for molecular studies for ETV6-NTRK3. Fusion gene was demonstrated in three cases, two had been erroneously diagnosed as poorly granulated AciCC, and one as low grade MEC with microcystic pattern. Female gender predominated (3:1); one occurred in the parotid, two in minor salivary glands and one in the submaxillary gland; infiltrating borders, atypical mitosis and lymph node metastases were seen in the parotideal tumor. Two patients with major salivary gland tumors are alive and well at 10 and 20 months respectively, the two patients with minor salivary gland tumors are lost. It can be concluded that is important to think in MASC in poorly granulated AciCC and low grade MEC with microcystic pattern. Immunohistochemisty studies confirm the diagnosis, preferentially supported by molecular studies. MASC may follow aggressive behavior or transform into a high grade neoplasm. Key words:Acinic cell carcinoma, ETV6-NTRK3, Mammary Analogue Secretory Carcinoma, secretory breast carcinoma. PMID:25481229

  20. Cholesteryl ester synthesis and hydrolysis in the rat mammary gland during pregnancy and lactation.

    Science.gov (United States)

    Botham, K M; Martínez, M J; Ochoa, B

    1993-09-01

    The activities of a lysosomal acid and two neutral cholesteryl ester hydrolases (microsomal and cytosolic) found in the mammary gland were studied in subcellular fractions prepared from tissue from rats at various stages of pregnancy, lactation, and after weaning the pups. The relationship between the activities of these enzymes and that of acyl coenzyme A: cholesterol acyl transferase (ACAT) was also investigated. Acid cholesteryl ester hydrolase activity was increased considerably in glands from lactating as compared to pregnant animals, and was sharply decreased 2 days after weaning. The microsomal neutral cholesteryl ester hydrolase activity followed a similar pattern, but took longer to return to pre-lactating values on weaning. In contrast, the activity of the cytosolic neutral cholesteryl ester hydrolase increased throughout pregnancy, then remained relatively constant in lactation and for 2 days after weaning. At 8 days post-weaning, however, activity was markedly decreased. No correlation between the changes in the activities of any the cholesteryl ester hydrolases and ACAT during mammary gland development was detected. The microsomal neutral cholesteryl ester hydrolase activity showed a strong positive linear correlation with the unesterified and esterified cholesterol content of the microsomal fraction. No relationship, however, was found between the cytosolic neutral cholesteryl ester hydrolase and the level of either form of cholesterol in the cytosol. In addition, there was no correlation between ACAT activity and microsomal cholesterol concentrations. These results provide evidence for an important role for the enzymes responsible for cholesteryl ester synthesis and hydrolysis in the mammary gland in the regulation of cholesterol metabolism and the provision of cholesterol for secretion into milk.

  1. Benign Bilateral Adenomyoepithelioma of the Mammary Gland in a Ring-tailed Lemur (Lemur catta).

    Science.gov (United States)

    Suárez-Bonnet, A; Grau-Bassas, E Rodríguez; Herráez, P; Quesada-Canales, O; Priestnall, S L; de Los Monteros, A Espinosa

    Naturally occurring mammary tumours are uncommon in prosimians. A 20-year-old female ring-tailed lemur (Lemur catta) developed bilateral enlargement of the mammary glands. Surgical removal revealed that both masses were comprised of multiple nodules and cystic areas that entirely replaced the normal glands. Histologically, a benign neoplastic biphasic cellular proliferation, composed of luminal-epithelial and basal-myoepithelial components, was identified. Immunohistochemical analysis for expression of cytokeratin (CK) AE1/AE3, CK7, CK5 + 8, CK14, vimentin, p63 and 14-3-3σ highlighted the biphasic nature of the neoplasm. A low mitotic count, low Ki67 labelling index, expression of oestrogen receptor-α, lack of expression of human epidermal growth factor receptor and a 3-year disease-free period without recurrence supported the benign nature of the tumour. Macroscopically, histologically and immunohistochemically this neoplasm resembled benign adenomyoepithelioma of the breast in women. This is the first complete report of a naturally occurring mammary tumour in a ring-tailed lemur. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Differential Mammary Gland Development in FVB and C57Bl/6 Mice: Implications for Breast Cancer Research

    Directory of Open Access Journals (Sweden)

    Breanne M. Anderson

    2011-10-01

    Full Text Available A growing body of research suggests a linkage between pubertal mammary gland development and environmental factors such as diet as modifiers of long term breast cancer risk. Much of this research is dependent upon mouse models, which may vary between studies. However, effects may be strain dependent and further modified by diet, which has not been previously examined. Therefore, the objective of the present study was to determine whether mammary gland development differs between FVB and C57Bl/6 strains on diets containing either n-6 or n-3 polyunsaturated fats. Developmental measures related to onset of puberty and mammary gland development differed between strains. Mice fed the n-3 polyunsaturated fatty acids (PUFA diet were shown to have lower numbers of terminal end buds, a marker of mammary gland development. This study helps to further clarify differences in development and dietary response between FVB and C57Bl/6 mice in order to more appropriately relate mammary gland research to human populations.

  3. Automated segmentation of mammary gland regions in non-contrast torso CT images based on probabilistic atlas

    Science.gov (United States)

    Zhou, X.; Kan, M.; Hara, T.; Fujita, H.; Sugisaki, K.; Yokoyama, R.; Lee, G.; Hoshi, H.

    2007-03-01

    The identification of mammary gland regions is a necessary processing step during the anatomical structure recognition of human body and can be expected to provide the useful information for breast tumor diagnosis. This paper proposes a fully-automated scheme for segmenting the mammary gland regions in non-contrast torso CT images. This scheme calculates the probability for each voxel belonging to the mammary gland or other regions (for example pectoralis major muscles) in CT images and decides the mammary gland regions automatically. The probability is estimated from the location of the mammary gland and pectoralis major muscles in CT images. The location (named as a probabilistic atlas) is investigated from the pre-segmentation results in a number of different CT scans and the CT number distribution is approximated using a Gaussian function. We applied this scheme to 66 patient cases (female, age: 40-80) and evaluated the accuracy by using the coincidence rate between the segmented result and gold standard that is generated manually by a radiologist for each CT case. The mean value of the coincidence rate was 0.82 with the standard deviation of 0.09 for 66 CT cases.

  4. Extracellular matrix control of mammary gland morphogenesis and tumorigenesis: insights from imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ghajar, Cyrus M; Bissell, Mina J

    2008-10-23

    The extracellular matrix (ECM), once thought to solely provide physical support to a tissue, is a key component of a cell's microenvironment responsible for directing cell fate and maintaining tissue specificity. It stands to reason, then, that changes in the ECM itself or in how signals from the ECM are presented to or interpreted by cells can disrupt tissue organization; the latter is a necessary step for malignant progression. In this review, we elaborate on this concept using the mammary gland as an example. We describe how the ECM directs mammary gland formation and function, and discuss how a cell's inability to interpret these signals - whether as a result of genetic insults or physicochemical alterations in the ECM - disorganizes the gland and promotes malignancy. By restoring context and forcing cells to properly interpret these native signals, aberrant behavior can be quelled and organization re-established. Traditional imaging approaches have been a key complement to the standard biochemical, molecular, and cell biology approaches used in these studies. Utilizing imaging modalities with enhanced spatial resolution in live tissues may uncover additional means by which the ECM regulates tissue structure, on different length scales, through its pericellular organization (short-scale) and by biasing morphogenic and morphostatic gradients (long-scale).

  5. Cell–Matrix Interactions in Mammary Gland Development and Breast Cancer

    Science.gov (United States)

    Muschler, John; Streuli, Charles H.

    2010-01-01

    The mammary gland is an organ that at once gives life to the young, but at the same time poses one of the greatest threats to the mother. Understanding how the tissue develops and functions is of pressing importance in determining how its control mechanisms break down in breast cancer. Here we argue that the interactions between mammary epithelial cells and their extracellular matrix (ECM) are crucial in the development and function of the tissue. Current strategies for treating breast cancer take advantage of our knowledge of the endocrine regulation of breast development, and the emerging role of stromal–epithelial interactions (Fig. 1). Focusing, in addition, on the microenvironmental influences that arise from cell–matrix interactions will open new opportunities for therapeutic intervention. We suggest that ultimately a three-pronged approach targeting endocrine, growth factor, and cell-matrix interactions will provide the best chance of curing the disease. PMID:20702598

  6. CHARACTERIZATION OF MAMMARY GLAND TISSUE USING JOINT ESTIMATORS OF MINKOWSKI FUNCTIONALS

    Directory of Open Access Journals (Sweden)

    Torsten Mattfeldt

    2011-05-01

    Full Text Available A theoretical approach to estimate the Minkowski functionals, i.e., area fraction, specifc boundary length and specifc Euler number in 2D, and their asymptotic covariance matrix proposed by Spodarev and Schmidt (2005 and Pantle et al. (2006a;b is applied to real image data. These two-dimensional images show mammary gland tissue and should be classifed automatically as tumor-free or mammary cancer, respectively. The estimation procedure is illustrated step-by-step and the calculations are described in detail. To reduce dependencies from chosen parameters, a least-squares approach is considered as recommended by Klenk et al. (2006. Emphasis is placed on the detailed description of the estimation procedure and the application of the theory to real image data.

  7. Bifunctional role of ephrin A1-Eph system in stimulating cell proliferation and protecting cells from cell death through the attenuation of ER stress and inflammatory responses in bovine mammary epithelial cells.

    Science.gov (United States)

    Kang, Minkyung; Jeong, Wooyoung; Bae, Hyocheol; Lim, Whasun; Bazer, Fuller W; Song, Gwonhwa

    2018-03-01

    Structural and functional development of the mammary gland is constant in the mammary gland life cycle. Eph receptors and their ligands, ephrins, control events through cell-to-cell interactions during embryonic development, and adult tissue homeostasis; however, little information on participation of ephrin A1, a representative ligand of the Eph receptor, in the development and function of normal mammary glands is known. In this study, we demonstrated functional effects of the ephrin A1-Eph system and mechanisms of its action on bovine mammary epithelial (MAC-T) cells. The in vitro cultured MAC-T cells expressed the ephrin A1 ligand and EphA1, A2, A4, A7, and A8 among the eight members of the Eph A family. Our results revealed that ephrin A1 induced MAC-T cell cycle progression and stimulated cell proliferation with abundant expression of nucleic PCNA and cyclin D1 proteins. Additionally, ephrin A1 induced activation of intracellular signaling molecules involved in PI3 K/AKT and MAPK signaling, and the proliferation-stimulating effect of ephrin A1 was mediated by activation of these pathways. Furthermore, ephrin A1 influenced expression and activation of various ER stress-related proteins and protected MAC-T cells from stress-induced cell death. Finally, ephrin A1 alleviated LPS-induced cell death through down-regulation of inflammatory cytokines. In conclusion, the results of this study suggest that the Eph A-ephrin A1 system is a positive factor in the increase and maintenance of epithelial cells in mammary glands of cows; the signaling system contributes to development, remodeling, and functionality of normal mammary glands and could overcome mastitis in cows and other mammals. © 2017 Wiley Periodicals, Inc.

  8. Presence of hyperplastic pectoral mammary glands in a white-footed mouse (Peromyscus leucopus) from a Superfund Site in Oklahoma, USA.

    Science.gov (United States)

    Hays, Kimberly A; Breshears, Melanie A

    2011-01-01

    Laboratory experiments have documented the effects of hormones and endocrine-disrupting compounds on mammary development in mammals. However, few observations of mammary hyperplasia have been presented for wild rodents. We describe hyperplastic mammary glands in a wild-caught white-footed mouse (Peromyscus leucopus) from an area contaminated with heavy metals.

  9. [Treatment of fibroepithelial hyperplasia (FEH) of the mammary gland in the cat with the progesterone antagonist Aglépristone (Alizine)].

    Science.gov (United States)

    Meisl, D; Hubler, M; Arnold, S

    2003-03-01

    Three cases of fibroepithelial hyperplasia (FEH) of the mammary gland in the cat are reported. A one year old female cat had a distinct enlargement of the middle mammary glands, one on each side, 5 days after the first estrus. One week later the cat was treated with medroxyprogesterone acetate (Depo-Promone). The affected glands, along with the remaining glands, increased further in size. A five year old female cat was treated with Proligeston (Covinan) for the suppression of estrus. Two weeks later fibroepithelial hyperplasia occurred in two glands, one with a well demarcated ulceration. A seven months old male cat was treated with delmadinon acetate (Tarden) because of urine spraying. Two months later he had enlargement of all mammary glands. All three cats were treated with the progesterone antagonist Aglépristone (Alizine). Within 5 to 11 weeks the mammary glands had regressed to normal.

  10. Rac1 Controls Both the Secretory Function of the Mammary Gland and Its Remodeling for Successive Gestations.

    OpenAIRE

    Akhtar, Nasreen; Li, Weiping; Mironov, Aleksander; Streuli, Charles H.

    2016-01-01

    Summary An important feature of the mammary gland is its ability to undergo repeated morphological changes during each reproductive cycle with profound tissue expansion in pregnancy and regression in involution. However, the mechanisms that determine the tissue's cyclic regenerative capacity remain elusive. We have now discovered that Cre-Lox ablation of Rac1 in mammary epithelia causes gross enlargement of the epithelial tree and defective alveolar regeneration in a second pregnancy. Archite...

  11. Retrospective evaluation of adjunctive doxorubicin for the treatment of feline mammary gland adenocarcinoma: 67 cases.

    Science.gov (United States)

    Novosad, C Andrew; Bergman, Philip J; O'Brien, Maura G; McKnight, Joanne A; Charney, Sarah C; Selting, Kim A; Graham, Joanne C; Correa, Stephanie S; Rosenberg, Mona P; Gieger, Tracy L

    2006-01-01

    Medical records for 67 cats with histologically confirmed mammary gland adenocarcinomas treated with adjunctive doxorubicin from June 1994 through December 2002 were reviewed. Data were examined to evaluate factors influencing disease-free interval (DFI) and survival time. The Kaplan-Meier median survival time of cats that received surgery and doxorubicin was 448 days. The Kaplan-Meier median DFI was 255 days. Significant univariate prognostic factors for DFI included histological subtype, completion of initial chemotherapy, development of metastatic disease, and location of metastatic disease. Significant univariate prognostic factors for survival included tumor volume, the development of metastatic disease, and location of metastatic disease.

  12. System of polarization phasometry of polycrystalline blood plasma networks in mammary gland pathology diagnostics

    Science.gov (United States)

    Zabolotna, Natalia I.; Oliinychenko, Bogdan P.; Radchenko, Kostiantyn O.; Krasnoshchoka, Anastasiia K.; Shcherba, Olga K.

    2015-09-01

    The polarizing phase meter system of polycrystalline networks of human blood plasma which is used for the mammary gland pathology diagnostics was proposed in this paper. Increasing the accuracy of the phase value determination was achieved using a combination of low coherent source of radiation and circularly polarized probing of biological object. Thus, high informativity of polarizing phase meter system for the diagnosis of breast pathology using the phase mapping of the human blood plasma films were determined, thereafter statistical, correlational, fractal structure analysis of the obtained phase maps was carried out and the quantitative criterias of the phase diagnostics and differentiation of the breast pathological conditions were determined too.

  13. Pleiotropic effects of polymorphism of the gene diacylglycerol-O-transferase 1 (DGAT1) in the mammary gland tissue of dairy cows

    NARCIS (Netherlands)

    Mach Casellas, N.; Blum, Y.; Bannink, A.; Causeur, D.; Houee-Bigot, M.; Lagarrigue, S.; Smits, M.A.

    2012-01-01

    Microarray analysis was used to identify genes whose expression in the mammary gland of Holstein-Friesian dairy cows was affected by the nonconservative Ala to Lys amino acid substitution at position 232 in exon VIII of the diacylglycerol-O-transferase 1 (DGAT1) gene. Mammary gland biopsies of 9

  14. Akt1 is essential for postnatal mammary gland development, function, and the expression of Btn1a1.

    Directory of Open Access Journals (Sweden)

    Jessica LaRocca

    Full Text Available Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays critical roles in the regulation of multiple cellular processes, and has previously been implicated in lactation and breast cancer development. In this study, we utilized Akt1+/+ and Akt1-/- C57/Bl6 female mice to assess the role that Akt1 plays in normal mammary gland postnatal development and function. We examined postnatal morphology at multiple time points, and analyzed gene and protein expression changes that persist into adulthood. Akt1 deficiency resulted in several mammary gland developmental defects, including ductal outgrowth and defective terminal end bud formation. Adult Akt1-/- mammary gland composition remained altered, exhibiting fewer alveolar buds coupled with increased epithelial cell apoptosis. Microarray analysis revealed that Akt1 deficiency altered expression of genes involved in numerous biological processes in the mammary gland, including organismal development, cell death, and tissue morphology. Of particular importance, a significant decrease in expression of Btn1a1, a gene involved in milk lipid secretion, was observed in Akt1-/- mammary glands. Additionally, pseudopregnant Akt1-/- females failed to induce Btn1a1 expression in response to hormonal stimulation compared to their wild-type counterparts. Retroviral-mediated shRNA knockdown of Akt1 and Btn1a1 in MCF-7 human breast epithelial further illustrated the importance of Akt1 in mammary epithelial cell proliferation, as well as in the regulation of Btn1a1 and subsequent expression of ß-casein, a gene that encodes for milk protein. Overall these findings provide mechanistic insight into the role of Akt1 in mammary morphogenesis and function.

  15. Low-dose BPA exposure alters the mesenchymal and epithelial transcriptomes of the mouse fetal mammary gland.

    Directory of Open Access Journals (Sweden)

    Perinaaz R Wadia

    Full Text Available Exposure of rodent fetuses to low doses of the endocrine disruptor bisphenol A (BPA causes subtle morphological changes in the prenatal mammary gland and results in pre-cancerous and cancerous lesions during adulthood. To examine whether the BPA-induced morphological alterations of the fetal mouse mammary glands are a associated with changes in mRNA expression reflecting estrogenic actions and/or b dependent on the estrogen receptor α (ERα, we compared the transcriptomal effects of BPA and the steroidal estrogen ethinylestradiol (EE2 on fetal mammary tissues of wild type and ERα knock-out mice. Mammary glands from fetuses of dams exposed to vehicle, 250 ng BPA/kg BW/d or 10 ng EE2/kg BW/d from embryonic day (E 8 were harvested at E19. Transcriptomal analyses on the ductal epithelium and periductal stroma revealed altered expression of genes involved in the focal adhesion and adipogenesis pathways in the BPA-exposed stroma while genes regulating the apoptosis pathway changed their expression in the BPA-exposed epithelium. These changes in gene expression correlated with previously reported histological changes in matrix organization, adipogenesis, and lumen formation resulting in enhanced maturation of the fat-pad and delayed lumen formation in the epithelium of BPA-exposed fetal mammary glands. Overall similarities in the transcriptomal effects of BPA and EE2 were more pronounced in the epithelium, than in the stroma. In addition, the effects of BPA and EE2 on the expression of various genes involved in mammary stromal-epithelial interactions were suppressed in the absence of ERα. These observations support a model whereby BPA and EE2 act directly on the stroma, which expresses ERα, ERβ and GPR30 in fetal mammary glands, and that the stroma, in turn, affects gene expression in the epithelium, where ERα and ERβ are below the level of detection at this stage of development.

  16. B-mode and Doppler sonography of the mammary glands in dairy goats for mastitis diagnosis.

    Science.gov (United States)

    Santos, V J C; Simplício, K; Sanchez, D; Coutinho, L; Teixeira, P; Barros, F; Almeida, V; Rodrigues, L; Bartlewski, P; Oliveira, M; Feliciano, M; Vicente, W

    2015-04-01

    This study aimed to evaluate the sonographic characteristics of the udder and teats and to determine the Doppler indexes of mammary artery in healthy and undergoing subclinical and clinical mastitis goats. Thirty animals among Saanen and Alpine Brown goats were arranged in three groups, healthy goats (HG), goats with subclinical mastitis (SMG) and goats with clinical mastitis (CMG). Using the B-mode, the sonographic characteristics (echotexture and echogenicity) and biometry (diameter and area of the udder cistern, diameter and area of the teat cistern and thickness of the teat wall) were evaluated. Using Doppler ultrasonography, the vascular indexes of the mammary artery were obtained. It was observed hyperechogenicity with solid component in the gland cistern when comparing animals with clinical mastitis and healthy mammary tissue. Regarding the echotexture of the breast tissue, there was heterogeneity in the mammary parenchyma on the three groups, for the milk, it was observed homogeneity for animals on HG and SMG and heterogeneity for animals on CMG. Grey-scale quantitative assessment revealed increase in echogenicity (mean value) for all the structures when comparing the three groups. Biometry did not reveal statistical difference between groups, for none of the evaluated structures. Doppler examination of the mammary artery showed the decrease of end diastolic velocity and raise of pulsatility index between groups. The association of B-mode and Doppler ultrasonography is useful for the evaluation of the udder of dairy goats with mastitis. It is a sensitive and specific method for the study of this disease. Doppler mode was unable to establish reliable criteria for diagnosis of subclinical mastitis. Moreover, the quantification of echogenicity is a useful technique for the evaluation of the milk in animals with mastitis; therefore, it is suggested that it can be used as complementary technique for the diagnosis of mastitis in goats. © 2015 Blackwell Verlag

  17. Retinoids, retinoid analogs, and lactoferrin interact and differentially affect cell viability of 2 bovine mammary cell types in vitro.

    Science.gov (United States)

    Wang, Y; Baumrucker, C R

    2010-07-01

    Two bovine mammary cell types (BME-UV1 and MeBo cells) were used to evaluate the effect of natural retinoids, retinoid analogs, and bovine lactoferrin (bLf) on cell viability in vitro. Experiments with Alamar Blue showed a linear relationship between fluorescence and cell viability index. The BME-UV1 cells exhibited twice the metabolic activity but required half the doubling time of the MeBo cells. The BME-UV1 cells were very sensitive to all-trans retinoic acid (atRA) inhibition of cell viability (Pretinoid-induced inhibition of cell viability, depending on the type of bovine mammary cell studied.

  18. Induction of a Pregnancy-Like Mammary Gland Differentiation by Docosapentaenoic Omega-3 Fatty Acid

    Science.gov (United States)

    2008-09-01

    Thirteen-and 17- week old vi rgin control mice and a ge-matched transgenic mice were sacrificed, inguinal mammar y glands were remo ved. Total protein...Cambrex, San Diego, CA, USA): bovine pituitary extract (52 lgÆmL)1), insulin (5 lgÆmL)1), epidermal growth factor (10 ngÆmL)1), and hydrocortisone (1

  19. Human breast cancer cells are redirected to mammary epithelial cells upon interaction with the regenerating mammary gland microenvironment in-vivo.

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    Karen M Bussard

    Full Text Available Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display 'normal' behavior when placed into 'normal' ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for 'normal' gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo.

  20. X-ray fluorescence microscopy reveals accumulation and secretion of discrete intracellular zinc pools in the lactating mouse mammary gland.

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    Nicholas McCormick

    2010-06-01

    Full Text Available The mammary gland is responsible for the transfer of a tremendous amount of zinc ( approximately 1-3 mg zinc/day from maternal circulation into milk during lactation to support the growth and development of the offspring. When this process is compromised, severe zinc deficiency compromises neuronal development and immune function and increases infant morbidity and/or mortality. It remains unclear as to how the lactating mammary gland dynamically integrates zinc import from maternal circulation with the enormous amount of zinc that is secreted into milk.Herein we utilized X-ray fluorescence microscopy (XFM which allowed for the visualization and quantification of the process of zinc transfer through the mammary gland of the lactating mouse. Our data illustrate that a large amount of zinc first accumulates in the mammary gland during lactation. Interestingly, this zinc is not cytosolic, but accumulated in large, discrete sub-cellular compartments. These zinc pools were then redistributed to small intracellular vesicles destined for secretion in a prolactin-responsive manner. Confocal microscopy identified mitochondria and the Golgi apparatus as the sub-cellular compartments which accumulate zinc; however, zinc pools in the Golgi apparatus, but not mitochondria are redistributed to vesicles destined for secretion during lactation.Our data directly implicate the Golgi apparatus in providing a large, mobilizable zinc storage pool to assist in providing for the tremendous amount of zinc that is secreted into milk. Interestingly, our study also provides compelling evidence that mitochondrial zinc pools expand in the mammary gland during lactation which we speculate may play a role in regulating mammary gland function.

  1. Comparative Transcriptome Profiling of Dairy Goat MicroRNAs from Dry Period and Peak Lactation Mammary Gland Tissues

    Science.gov (United States)

    Guo, Wenjiao; Sun, Jiajie; Huang, Yongzhen; Wang, Jing; Huang, Tinghua; Lei, Chuozhao; Fang, Xingtang; Chen, Hong

    2012-01-01

    Background MicroRNAs (miRNAs) are small noncoding RNA molecules that serve as important post-transcriptional gene expression regulators by targeting messenger RNAs for post-transcriptional endonucleolytic cleavage or translational inhibition. miRNAs play important roles in many biological processes. Extensive high-throughput sequencing studies of miRNAs have been performed in several animal models. However, little is known about the diversity of these regulatory RNAs in goat (Capra hircus), which is one of the most important agricultural animals and the oldest domesticated species raised worldwide. Goats have long been used for their milk, meat, hair (including cashmere), and skins throughout much of the world. Results In this study, two small RNA libraries were constructed based on dry period and peak lactation dairy goat mammary gland tissues and sequenced using the Illumina-Solexa high-throughput sequencing technology. A total of 346 conserved and 95 novel miRNAs were identified in the dairy goat. miRNAs expression was confirmed by qRT-PCR in nine tissues and in the mammary gland during different stages of lactation. In addition, several candidate miRNAs that may be involved in mammary gland development and lactation were found by comparing the miRNA expression profiles in different tissues and developmental stages of the mammary gland. Conclusions This study reveals the first miRNAs profile related to the biology of the mammary gland in the dairy goat. The characterization of these miRNAs could contribute to a better understanding of the molecular mechanisms of lactation physiology and mammary gland development in the dairy goat. PMID:23300659

  2. Mammary Analogue Secretory Carcinoma of Parotid Gland in a Teenage Boy.

    Science.gov (United States)

    Mahmood, Humera; Fatima, Hadia; Faheem, Mohammad

    2017-09-01

    Mammary analogue secretory carcinoma (MASC) is a rare salivary gland malignancy that exhibits resemblance with secretory carcinoma of the breast (SC) due to the presence of ETV6-NTRK3 gene fusion, formerly classified as acinic cell carcinoma. It is a slowly growing painless tumor that exhibits wide range of clinical behavior. This tumor typically affects middle aged people. Less than 100 such cases have been reported in the literature so far with only 8 case reports of patients less than 19 years of age. Very little is known about the clinical management of such cases. We hereby report a case of 15-year boy who had been managed for MASC of left parotid gland with exision.

  3. Mammary analogue secretory carcinoma of the salivary glands: a diagnostic dilemma.

    Science.gov (United States)

    Hindocha, N; Wilson, M H; Pring, M; Hughes, C W; Thomas, S J

    2017-04-01

    Mammary analogue secretory carcinoma (MASC) is a recently identified salivary gland neoplasm that can mimic other salivary gland tumours such as acinic cell carcinoma and cystadenocarcinoma. It is distinguished from these by differences in immunohistochemical profile and the identification of an ETV6-NTRK3 translocation (12;15)(p13;q25), which is also found in secretory carcinomas of the breast. Previous publications have suggested that MASC tumours have similar biological behaviour to acinic cell carcinoma. We report two cases of MASC that affected the upper lip, and showed an infiltrative and locally aggressive growth pattern that required several operations to ensure clearance of microscopic tumour cells. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  4. Microbial agents in macroscopically healthy mammary gland tissues of small ruminants.

    Science.gov (United States)

    Spuria, Liliana; Biasibetti, Elena; Bisanzio, Donal; Biasato, Ilaria; De Meneghi, Daniele; Nebbia, Patrizia; Robino, Patrizia; Bianco, Paolo; Lamberti, Michele; Caruso, Claudio; Di Blasio, Alessia; Peletto, Simone; Masoero, Loretta; Dondo, Alessandro; Capucchio, Maria Teresa

    2017-01-01

    Health of mammary glands is fundamental for milk and dairy products hygiene and quality, with huge impacts on consumers welfare. This study aims to investigate the microbial agents (bacteria, fungi and lentiviruses) isolated from 89 macroscopically healthy udders of regularly slaughtered small ruminants (41 sheep, 48 goats), also correlating their presence with the histological findings. Multinomial logistic regression was applied to evaluate the association between lesions and positivity for different microbial isolates, animal age and bacteria. Twenty-five samples were microbiologically negative; 138 different bacteria were isolated in 64 positive udders. Coagulase-negative staphylococci were the most prevalent bacteria isolated (46.42%), followed by environmental opportunists (34.76%), others (10.14%) and pathogens (8.68%). Most mammary glands showed coinfections (75%). Lentiviruses were detected in 39.3% of samples. Histologically, chronic non-suppurative mastitis was observed in 45/89 glands, followed by chronic mixed mastitis (12/89) and acute suppurative mastitis (4/89). Only 28 udders were normal. Histological lesions were significantly associated with the animal species and lentiviruses and coagulase-negative staphylococci infections. Goats had significantly higher risk to show chronic mixed mastitis compared to sheep. Goats showed a significantly lower risk (OR = 0.26; 95% CI [0.06-0.71]) of being infected by environmental opportunists compared to sheep, but higher risk (OR = 10.87; 95% CI [3.69-37.77]) of being infected with lentiviruses. The results of the present study suggest that macroscopically healthy glands of small ruminants could act as a reservoir of microbial agents for susceptible animals, representing a potential risk factor for the widespread of acute or chronic infection in the flock.

  5. Microbial agents in macroscopically healthy mammary gland tissues of small ruminants

    Directory of Open Access Journals (Sweden)

    Liliana Spuria

    2017-11-01

    Full Text Available Background Health of mammary glands is fundamental for milk and dairy products hygiene and quality, with huge impacts on consumers welfare. Methods This study aims to investigate the microbial agents (bacteria, fungi and lentiviruses isolated from 89 macroscopically healthy udders of regularly slaughtered small ruminants (41 sheep, 48 goats, also correlating their presence with the histological findings. Multinomial logistic regression was applied to evaluate the association between lesions and positivity for different microbial isolates, animal age and bacteria. Results Twenty-five samples were microbiologically negative; 138 different bacteria were isolated in 64 positive udders. Coagulase-negative staphylococci were the most prevalent bacteria isolated (46.42%, followed by environmental opportunists (34.76%, others (10.14% and pathogens (8.68%. Most mammary glands showed coinfections (75%. Lentiviruses were detected in 39.3% of samples. Histologically, chronic non-suppurative mastitis was observed in 45/89 glands, followed by chronic mixed mastitis (12/89 and acute suppurative mastitis (4/89. Only 28 udders were normal. Histological lesions were significantly associated with the animal species and lentiviruses and coagulase-negative staphylococci infections. Goats had significantly higher risk to show chronic mixed mastitis compared to sheep. Goats showed a significantly lower risk (OR = 0.26; 95% CI [0.06–0.71] of being infected by environmental opportunists compared to sheep, but higher risk (OR = 10.87; 95% CI [3.69–37.77] of being infected with lentiviruses. Discussion The results of the present study suggest that macroscopically healthy glands of small ruminants could act as a reservoir of microbial agents for susceptible animals, representing a potential risk factor for the widespread of acute or chronic infection in the flock.

  6. The plasticizer butyl benzyl phthalate induces genomic changes in rat mammary gland after neonatal/prepubertal exposure

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    Lamartiniere Coral A

    2007-12-01

    Full Text Available Abstract Background Phthalate esters like n-butyl benzyl phthalate (BBP are widely used plasticizers. BBP has shown endocrine-disrupting properties, thus having a potential effect on hormone-sensitive tissues. The aim of this study is to determine the effect of neonatal/prepubertal exposure (post-natal days 2–20 to BBP on maturation parameters and on the morphology, proliferative index and genomic signature of the rat mammary gland at different ages of development (21, 35, 50 and 100 days. Results Here we show that exposure to BBP increased the uterine weight/body weight ratio at 21 days and decreased the body weight at time of vaginal opening. BBP did not induce significant changes on the morphology of the mammary gland, but increased proliferative index in terminal end buds at 35 days and in lobules 1 at several ages. Moreover, BBP had an effect on the genomic profile of the mammary gland mainly at the end of the exposure (21 days, becoming less prominent thereafter. By this age a significant number of genes related to proliferation and differentiation, communication and signal transduction were up-regulated in the glands of the exposed animals. Conclusion These results suggest that BBP has an effect in the gene expression profile of the mammary gland.

  7. Proteolytic maturation of protein C upon engineering the mouse mammary gland to express furin.

    Science.gov (United States)

    Drews, R; Paleyanda, R K; Lee, T K; Chang, R R; Rehemtulla, A; Kaufman, R J; Drohan, W N; Luboń, H

    1995-11-07

    Endoproteolytic processing of the human protein C (HPC) precursor to its mature form involves cleavage of the propeptide after amino acids Lys-2-Arg-1 and removal of a Lys156-Arg157 dipeptide connecting the light and heavy chains. This processing was inefficient in the mammary gland of transgenic mice and pigs. We hypothesized that the protein processing capacity of specific animal organs may be improved by the coexpression of selected processing enzymes. We tested this by targeting expression of the human proprotein processing enzyme, named paired basic amino acid cleaving enzyme (PACE)/furin, or an enzymatically inactive mutant, PACEM, to the mouse mammary gland. In contrast to mice expressing HPC alone, or to HPC/PACEM bigenic mice, coexpression of PACE with HPC resulted in efficient conversion of the precursor to mature protein, with cleavage at the appropriate sites. These results suggest the involvement of PACE in the processing of HPC in vivo and represent an example of the engineering of animal organs into bioreactors with enhanced protein processing capacity.

  8. Clinical Classification of Diseases and Conditions of Mammary Glands in Children and Adolescents

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    Marina L. Travina

    2016-01-01

    Full Text Available The article describes the proposed current clinical classification of breast diseases and pathology in childhood and adolescence. The classification is based on the analysis of data obtained from the examination and follow-up monitoring of 6,126 children for up to 8 years. The clinical classification is recommended for widespread use in the work of primary care physicians who conduct follow-up monitoring. The use of this classification creates groups for referral to specialists for further examination and further treatment and follow-up monitoring. The classification is based on the separation of physiological (normal conditions and pathological processes, as well as on temporary deviations from normal development (temporary conditions not leading to pathological processes and anomalies in development of mammary glands and nipple-areolar complex. If any abnormalities are suspected, a patient shall be sent to a mammologist for further examination and US scanning. Control of growth and development of mammary glands in childhood and adolescence ensures early detection of abnormalities and allows necessary remedial measures to protect reproductive health.

  9. Investigation of hFVIII production in mammary glands of transgenic mice.

    Science.gov (United States)

    Mohammadian, Tahar; Rassi, Hossein

    2014-10-01

    Hemophilia A is an X-linked disorder affecting 1 in 10,000 males. The disease is caused by a defect or mutation of factor 8 or 9. Human factor 8 gene (hFVIII) is a relatively large gene consisting of 26 exons and approximately 2,351 amino acids with a length of 9 Kb mRNA. Expression of hFVIII in mammalian milk is becoming a widespread strategy for high-level production of hFVIII because of the most complex post-translational modifications. The aim of this study was the cloning and expression of hFVIII in mammary glands of two transgenic mice. To obtain a recombinant plasmid, first a plasmid carrying an FVIII gene fragment (pCMV6-hFVIII) was digested by EcoRI-SalI restriction enzymes and then the fragment was purified from agarose gel and inserted into a pUCWAP7 vector carrying a tissue-specific promoter (mWAP 4.1 kbp). After that, it was isolated by agarose gel and transferred into the murine zygotes by standard microinjection methods. Methods for expression of recombinant FVIII RT-PCR and ELISA were studied. The results show the successful expression of factor FVIII gene and its product in the mouse mammary glands.

  10. Nutritional and hormonal regulation of malic enzyme synthesis in rat mammary gland.

    Science.gov (United States)

    Lobato, M F; Ros, M; Moreno, F J; García-Ruíz, J P

    1986-06-01

    Cytosolic malic enzyme was purified from rat mammary gland by L-malate affinity chromatography. The pure enzyme obtained was used to produce a specific antiserum in a rabbit. Relative synthesis of malic enzyme in the mammary gland of mid-lactating rats was 0.097%, measured by labelling the enzyme in isolated acini. When food was removed, malic enzyme synthesis decreased to 35% and 20% of the control value at 4 and 6 h respectively. Incorporation of [3H]leucine into soluble proteins was constant during the first 6 h of starvation. When lactating rats (maintained with their pups) were starved for 24 h and then re-fed, the relative rate of enzyme synthesis increased 2.5-, 4-, and 4.5-fold at 3 h, 6 h and 18 h respectively after initiation of re-feeding. The relative rate of malic enzyme synthesis was about 50% of normal at 15 h after weaning, whereas the rate of synthesis of soluble proteins did not change. Administration of bromocriptine or adrenalectomy of lactating rats decreased the relative rate of synthesis of malic enzyme by 40% or 30% respectively; these effects were counteracted by hormone supplementation. Hormone therapy also caused an increase in the rate of incorporation of [3H]leucine into soluble proteins and in malic enzyme activity.

  11. Transgenesis of Tol2-mediated seamlessly constructed BAC mammary gland expression vectors in Mus musculus.

    Science.gov (United States)

    Yang, Yaohui; Wang, Wenyuan; Huang, Tian; Ruan, Weimin; Cao, Gengsheng

    2016-01-20

    Bacterial artificial chromosomes (BACs) are vectors that are capable of carrying gene fragments of up to 300 kb in size, and in theory, harbor cis-regulatory elements that are necessary for the expression of specific genes. Therefore, BACs can effectively alleviate or even eliminate the position effect induced by gene-integration, rendering these as ideal expression vectors of exogenous genes. However, the number of relevant studies involving BACs as vectors of exogenous genes are limited. In the present study, we converted the BAC regulatory region of the Mus musculus Wap gene into a mammary gland-specific expression vector. Using the galK-based positive-negative selection method, we seamlessly replaced the Wap gene in a BAC with Homo sapiens GPX3, MT2, and Luc genes while keeping the original mammary gland-specific regulatory sequence intact, without introducing any extra sequences (Loxp/Frt). To improve the efficiency of creating BAC transgenic mice, we used a Tol2 transposon system optimized for mammalian codons and eliminated 100 kb of sequence from the BAC 5' end (173 kb), which resulted in an 8.5% rate of successful gene transmission via pronuclear injection. The results of the present study indicate that seamlessly constructed BAC expression vectors can be used for the transmission of the GPX3 gene. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Unraveling the microenvironmental influences on the normal mammary gland and induction and progression of breast cancer

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    Weigelt, Britta; Bissell, Mina J.

    2008-06-26

    The normal mammary gland and invasive breast cancer are both complex 'organs' composed of multiple cell types as well as extracellular matrix (ECM) in three-dimensional (3D) space. Conventionally, both normal and malignant breast cells are studied in vitro as two-dimensional (2D) monolayers of epithelial cells, which results in the loss of structure and tissue function. Many laboratories are now investigating regulation of signaling function in normal mammary gland using 3D cultures. However, it is important also to assay malignant breast cells ex vivo in a physiologically relevant environment to more closely mimic tumor architecture, signal transduction regulation and tumor behavior in vivo. Here we present the potential of these 3D models for drug testing, target validation and guidance of patient selection for clinical trials. We argue also that in order to get full insight into the biology of the normal and malignant breast, and to create in vivo-like models for therapeutic approaches in humans, we need to continue to create more complex heterotypic models to approach the full context the cells encounter in the human body.

  13. Mammary analogue secretory carcinoma (MASC) of salivary gland in four Mexican patients.

    Science.gov (United States)

    Serrano-Arévalo, Mónica L; Mosqueda-Taylor, Adalberto; Domínguez-Malagón, Hugo; Michal, Michal

    2015-01-01

    The Clinco-pathological, immunohistochemical and molecular findings of four cases of Mammary Analogue Secretory Carcinoma (MASC) of salivary glands found in Mexico are described. The cases were extracted from 253 salivary gland tumors from a single institution in Mexico City. The 85 Candidates for initial selection were: low grade mucoepidermoid carcinoma (MEC) (N=70 ), Acinic cell cancinoma (AciCC) (N=14), papillary cystadenocarcinoma (N=1), and adenocarcinoma NOS (N=0). Tumors with some histological features consistent with MASC (N= 17, 6.7%) were studied by immunohistochemistry for mammaglobin, STAT5, and S-100 protein and four cases were positive (1.5%), thus the diagnosis of MASC was established, and these were submitted for molecular studies for ETV6-NTRK3. Fusion gene was demonstrated in three cases, two had been erroneously diagnosed as poorly granulated AciCC, and one as low grade MEC with microcystic pattern. Female gender predominated (3:1); one occurred in the parotid, two in minor salivary glands and one in the submaxillary gland; infiltrating borders, atypical mitosis and lymph node metastases were seen in the parotideal tumor. Two patients with major salivary gland tumors are alive and well at 10 and 20 months respectively, the two patients with minor salivary gland tumors are lost. It can be concluded that is important to think in MASC in poorly granulated AciCC and low grade MEC with microcystic pattern. Immunohistochemisty studies confirm the diagnosis, preferentially supported by molecular studies. MASC may follow aggressive behavior or transform into a high grade neoplasm.

  14. Effect of heat stress during the dry period on mammary gland development.

    Science.gov (United States)

    Tao, S; Bubolz, J W; do Amaral, B C; Thompson, I M; Hayen, M J; Johnson, S E; Dahl, G E

    2011-12-01

    Heat stress during the dry period negatively affects hepatic metabolism and cellular immune function during the transition period, and milk production in the subsequent lactation. However, the cellular mechanisms involved in the depressed mammary gland function remain unknown. The objective of the present study was to determine the effect of heat stress during the dry period on various indices of mammary gland development of multiparous cows. Cows were dried off approximately 46 d before expected calving and randomly assigned to 2 treatments, heat stress (HT, n=15) or cooling (CL, n=14), based on mature equivalent milk production. Cows in the CL treatment were provided with sprinklers and fans that came on when ambient temperatures reached 21.1°C, whereas HT cows were housed in the same barn without fans and sprinklers. After parturition, all cows were housed in a freestall barn with cooling. Rectal temperatures were measured twice daily (0730 and 1430 h) and respiration rates recorded at 1500 h on a Monday-Wednesday-Friday schedule from dry off to calving. Milk yield and composition were recorded daily up to 280 d in milk. Daily dry matter intake was measured from dry off to 42 d relative to calving. Mammary biopsies were collected at dry off, -20, 2, and 20 d relative to calving from a subset of cows (HT, n=7; CL, n=7). Labeling with Ki67 antigen and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling were used to evaluate mammary cell proliferation and apoptosis, respectively. The average temperature-humidity index during the dry period was 76.6 and not different between treatments. Heat-stressed cows had higher rectal temperatures in the morning (38.8 vs. 38.6°C) and afternoon (39.4 vs. 39.0°C), greater respiration rates (78.4 vs. 45.6 breath/min), and decreased dry matter intake (8.9 vs. 10.6 kg/d) when dry compared with CL cows. Relative to HT cows, CL cows had greater milk production (28.9 vs. 33.9 kg/d), lower milk protein

  15. Isoform-specific degradation of PR-B by E6-AP is critical for normal mammary gland development.

    Science.gov (United States)

    Ramamoorthy, Sivapriya; Dhananjayan, Sarath C; Demayo, Francesco J; Nawaz, Zafar

    2010-11-01

    E6-associated protein (E6-AP), which was originally identified as an ubiquitin-protein ligase, also functions as a coactivator of estrogen (ER-α) and progesterone (PR) receptors. To investigate the in vivo role of E6-AP in mammary gland development, we generated transgenic mouse lines that either overexpress wild-type (WT) human E6-AP (E6-AP(WT)) or ubiquitin-protein ligase-defective E6-AP (E6-AP(C833S)) in the mammary gland. Here we show that overexpression of E6-AP(WT) results in impaired mammary gland development. In contrast, overexpression of E6-AP(C833S) or loss of E6-AP (E6-AP(KO)) increases lateral branching and alveolus-like protuberances in the mammary gland. We also show that the mammary phenotypes observed in the E6-AP transgenic and knockout mice are due, in large part, to the alteration of PR-B protein levels. We also observed alteration in ER-α protein level, which might contribute to the observed mammary phenotype by regulating PR expression. Furthermore, E6-AP regulates PR-B protein levels via the ubiquitin-proteasome pathway. Additionally, we also show that E6-AP impairs progesterone-induced Wnt-4 expression by decreasing the steady state level of PR-B in both mice and in human breast cancer cells. In conclusion, we present the novel observation that E6-AP controls mammary gland development by regulating PR-B protein turnover via the ubiquitin proteasome pathway. For the first time, we show that the E3-ligase activity rather than the coactivation function of E6-AP plays an important role in the mammary gland development, and the ubiquitin-dependent PR-B degradation is not required for its transactivation functions. This mechanism appears to regulate normal mammogenesis, and dysregulation of this process may be an important contributor to mammary cancer development and progression.

  16. Differential expression of serotonin, tryptophan hydroxylase and monoamine oxidase A in the mammary gland of the Myotis velifer bat.

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    Cristián Vela Hinojosa

    Full Text Available The mammary gland has long drawn the attention of the scientific community due to the limited knowledge of some fundamental aspects involved in the control of its function. Myotis velifer, a microchiropteran species, provides an interesting model to study some of the regulatory factors involved in the control of the mammary gland cycle. Having an asynchronous, monoestrous reproductive pattern, female M. velifer bats undergo drastic morphological changes of the breast during the reproductive cycle. Current research on non-chiropteran mammals indicates that serotonin (5-HT plays a major role in the intraluminal volume homeostasis of the mammary gland during lactation; however, an analysis of both the expression and localization of the main components of the serotonergic system in the bat mammary gland is lacking. Thus, the objectives of the present study were: to describe the gross and histological anatomy of the mammary gland of M. velifer to establish the lactation period for this species; to analyze the distribution and expression of the main serotonergic components in the mammary tissues of these bats under the physiological conditions of lactation, involution and the resting phase; and to provide information on the involvement of 5-HT in the regulation of the physiological function of this organ. To assess the expression and localization of serotonergic components, multiple immunofluorescence, Western blot and HPLC methods were used. 5-HT and the enzyme that catalyzes its synthesis (TPH were located in both myoepithelial and luminal epithelial cells, while the enzyme responsible for the catabolism of this neurohormone (MAO A was found in luminal epithelial cells as well as in secreted products. We also found an increased expression of serotonergic components during lactation, indicating that elements of the serotonergic system may play an important role in lactation in this species of bat in a way similar to that of other mammal species.

  17. Estrogen and estrogen plus progestin act directly on the mammary gland to increase proliferation in a postmenopausal mouse model.

    Science.gov (United States)

    Raafat, A M; Li, S; Bennett, J M; Hofseth, L J; Haslam, S Z

    2001-04-01

    Hormone replacement therapy (HRT) with ovarian hormones is an important therapeutic modality for postmenopausal women. However, a negative side effect of HRT is an increased risk of breast cancer. Surgical induction of menopause by ovariectomy (OVX) in mice is an experimental model that may provide insights into the effects of hormone replacement therapy on the human breast. We have developed a mouse model of early and late postmenopausal states to investigate the effects of HRT on the normal mammary gland. The purpose of this study was to determine if HRT-induced proliferation was due to the direct action of the hormones on the mammary gland, or mediated systemically by hormones or growth factors produced elsewhere in the body. Estrogen (E) or E plus the synthetic progestin, R5020, were implanted directly into the mammary glands of early (1 week post OVX) and late (5 week post OVX) postmenopausal mice instead of administration by injection. We report that responses of early and late postmenopausal mice to implanted hormones were the same as those observed previously with systemically administered hormones. Implanted E conferred an enhanced proliferative response in the late postmenopausal gland characterized morphologically by enlarged duct ends. E+R5020 implants induced similar degrees of cell proliferation in both postmenopausal states but the morphological responses differed. Ductal sidebranching was observed in early postmenopausal mice, whereas duct end enlargement was observed in late postmenopausal mice. The differences in morphological response to E+R5020 in 5 week post OVX were associated with an inability of E to induce progesterone receptors (PR) in the late postmenopausal gland. The responses of the late postmenopausal glands to E and E+P were very similar to that observed previously in immature pubertal glands in ovary-intact mice. In pubertal mice, PR cannot be induced by E unless the mammary gland is pre-treated with EGF-containing implants

  18. Hypothyroidism decreases JAK/STAT signaling pathway in lactating rat mammary gland.

    Science.gov (United States)

    Campo Verde Arboccó, Fiorella; Persia, Fabio Andres; Hapon, María Belén; Jahn, Graciela A

    2017-07-15

    Thyroid pathologies have deleterious effects on lactation. Especially hypothyroidism (HypoT) induces premature mammary involution at the end of lactation and decreases milk production and quality in mid lactation. Milk synthesis is controlled by JAK2/STAT5 signaling pathway and prolactin (PRL), which activates the pathway. In this work we analyzed the effect of chronic 6-propyl-2-thiouracil (PTU)-induced HypoT on PRL signaling pathway on mammary glands from rats on lactation (L) days 2, 7 and 14. HypoT decreased prolactin receptor expression, and expression and activation of Stat5a/b protein. Expression of members of the SOCS-CIS family, inhibitors of the JAK-STAT pathway, decreased in L2 and L7, possibly as a compensatory response of the mammary cells to maintain PRL responsiveness. However, on L14, the level of these inhibitors was normal and the transcription of α-lactoalbumin (lalba), a target gene of the PRL pathway, decreased by half. HypoT altered the transcriptional capacity of the cell and decreased mRNA levels of Prlr and Stat5b on L14. Stat5b gene has functional thyroid hormone response elements in the regulatory regions, that bind thyroid hormone receptor β (TRβ) differentially and in a thyroid hormone dependent manner. The overall decrease in the PRL signaling pathway and consequently in target gene (lalba) mRNA transcription explain the profound negative impact of HypoT on mammary function through lactation. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Expression of Autoactivated Stromelysin-1 in Mammary Glands of Transgenic Mice Leads to a Reactive Stroma During Early Development

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    Thomasset, N.; Lochter, A.; Sympson, C.J.; Lund, L.R.; Williams, D.R.; Behrendtsen, O.; Werb, Z.; Bissell, M.J.

    1998-04-24

    Extracellular matrix and extracellular matrix-degrading matrix metalloproteinases play a key role in interactions between the epithelium and the mesenchyme during mammary gland development and disease. In patients with breast cancer, the mammary mesenchyme undergoes a stromal reaction, the etiology of which is unknown. We previously showed that targeting of an autoactivating mutant of the matrix metalloproteinase stromelysin-1 to mammary epithelia of transgenic mice resulted in reduced mammary function during pregnancy and development of preneoplastic and neoplastic lesions. Here we examine the cascade of alterations before breast tumor formation in the mammary gland stroma once the expression of the stromelysin-1 transgene commences. Beginning in postpubertal virgin animals, low levels of transgene expression in mammary epithelia led to increased expression of endogenous stromelysin-1 in stromal fibroblasts and up-regulation of other matrix metalloproteinases, without basement membrane disruption. These changes were accompanied by the progressive development of a compensatory reactive stroma, characterized by increased collagen content and vascularization in glands from virgin mice. This remodeling of the gland affected epithelial-mesenchymal communication as indicated by inappropriate expression of tenascin-C starting by day 6 of pregnancy. This, together with increased transgene expression, led to basement membrane disruption starting by day 15 of pregnancy. We propose that the highly reactive stroma provides a prelude to breast epithelial tumors observed in these animals. Epithelial development depends on an exquisite series of inductive and instructive interactions between the differentiating epithelium and the mesenchymal (stromal) compartment. The epithelium, which consists of luminal and myoepithelial cells, is separated from the stroma by a basement membrane (BM), which plays a central role in mammary gland homeostasis and gene expression. In vivo, stromal

  20. Bee Venom Decreases LPS-Induced Inflammatory Responses in Bovine Mammary Epithelial Cells.

    Science.gov (United States)

    Jeong, Chang Hee; Cheng, Wei Nee; Bae, Hyojin; Lee, Kyung Woo; Han, Sang Mi; Petriello, Michael C; Lee, Hong Gu; Seo, Han Geuk; Han, Sung Gu

    2017-10-28

    The world dairy industry has long been challenged by bovine mastitis, an inflammatory disease, which causes economic loss due to decreased milk production and quality. Attempts have been made to prevent or treat this disease with multiple approaches, primarily through increased abuse of antibiotics, but effective natural solutions remain elusive. Bee venom (BV) contains a variety of peptides (e.g., melittin) and shows multiple bioactivities, including prevention of inflammation. Thus, in the current study, it was hypothesized that BV can reduce inflammation in bovine mammary epithelial cells (MAC-T). To examine the hypothesis, cells were treated with LPS (1 μg/ml) to induce an inflammatory response and the anti-inflammatory effects of BV (2.5 and 5 μg/ml) were investigated. The cellular mechanisms of BV against LPS-induced inflammation were also investigated. Results showed that BV can attenuate expression of an inflammatory protein, COX2, and pro-inflammatory cytokines such as IL-6 and TNF-α. Activation of NF-κB, an inflammatory transcription factor, was significantly downregulated by BV in cells treated with LPS, through dephosphorylation of ERK1/2. Moreover, pretreatment of cells with BV attenuated LPS-induced production of intracellular reactive oxygen species (e.g., superoxide anion). These results support our hypothesis that BV can decrease LPS-induced inflammatory responses in bovine mammary epithelial cells through inhibition of oxidative stress, NF-κB, ERK1/2, and COX-2 signaling.

  1. c-Myc affects mRNA translation, cell proliferation and progenitor cell function in the mammary gland

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    Trumpp Andreas

    2009-09-01

    Full Text Available Abstract Background The oncoprotein c-Myc has been intensely studied in breast cancer and mouse mammary tumor models, but relatively little is known about the normal physiological role of c-Myc in the mammary gland. Here we investigated functions of c-Myc during mouse mammary gland development using a conditional knockout approach. Results Generation of c-mycfl/fl mice carrying the mammary gland-specific WAPiCre transgene resulted in c-Myc loss in alveolar epithelial cells starting in mid-pregnancy. Three major phenotypes were observed in glands of mutant mice. First, c-Myc-deficient alveolar cells had a slower proliferative response at the start of pregnancy, causing a delay but not a block of alveolar development. Second, while milk composition was comparable between wild type and mutant animals, milk production was reduced in mutant glands, leading to slower pup weight-gain. Electron microscopy and polysome fractionation revealed a general decrease in translational efficiency. Furthermore, analysis of mRNA distribution along the polysome gradient demonstrated that this effect was specific for mRNAs whose protein products are involved in milk synthesis. Moreover, quantitative reverse transcription-polymerase chain reaction analysis revealed decreased levels of ribosomal RNAs and ribosomal protein-encoding mRNAs in mutant glands. Third, using the mammary transplantation technique to functionally identify alveolar progenitor cells, we observed that the mutant epithelium has a reduced ability to repopulate the gland when transplanted into NOD/SCID recipients. Conclusion We have demonstrated that c-Myc plays multiple roles in the mouse mammary gland during pregnancy and lactation. c-Myc loss delayed, but did not block proliferation and differentiation in pregnancy. During lactation, lower levels of ribosomal RNAs and proteins were present and translation was generally decreased in mutant glands. Finally, the transplantation studies suggest a role

  2. Old and new stories: revelations from functional analysis of the bovine mammary transcriptome during the lactation cycle.

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    Massimo Bionaz

    Full Text Available The cow mammary transcriptome was explored at -30, -15, 1, 15, 30, 60, 120, 240, and 300 d relative to parturition. A total of 6,382 differentially expressed genes (DEG at a false discovery rate ≤ 0.001 were found throughout lactation. The greatest number of DEG (>3,500 DEG was observed at 60 and 120 d vs. -30 d with the largest change between consecutive time points observed at -15 vs. 1 d and 120 vs. 240 d. Functional analysis of microarray data was performed using the Dynamic Impact Approach (DIA. The DIA analysis of KEGG pathways uncovered as the most impacted and induced 'Galactose metabolism', 'Glycosylphosphatidylinositol (GPI-anchor biosynthesis', and 'PPAR signaling'; whereas, 'Antigen processing and presentation' was among the most inhibited. The integrated interpretation of the results suggested an overall increase in metabolism during lactation, particularly synthesis of carbohydrates and lipid. A marked degree of utilization of amino acids as energy source, an increase of protein export, and a decrease of the protein synthesis machinery as well cell cycle also were suggested by the DIA analysis. The DIA analysis of Gene Ontology and other databases uncovered an induction of Golgi apparatus and angiogenesis, and the inhibition of both immune cell activity/migration and chromosome modifications during lactation. All of the highly-impacted and activated functions during lactation were evidently activated at the onset of lactation and inhibited when milk production declined. The overall analysis indicated that the bovine mammary gland relies heavily on a coordinated transcriptional regulation to begin and end lactation. The functional analysis using DIA underscored the importance of genes associated with lactose synthesis, lipid metabolism, protein synthesis, Golgi, transport, cell cycle/death, epigenetic regulation, angiogenesis, and immune function during lactation.

  3. Comparison between conjugated linoleic acid and essential fatty acids in preventing oxidative stress in bovine mammary epithelial cells.

    Science.gov (United States)

    Basiricò, L; Morera, P; Dipasquale, D; Tröscher, A; Bernabucci, U

    2017-03-01

    Some in vitro and in vivo studies have demonstrated protective effects of conjugated linoleic acid (CLA) isomers against oxidative stress and lipid peroxidation. However, only a few and conflicting studies have been conducted showing the antioxidant potential of essential fatty acids. The objectives of the study were to compare the effects of CLA to other essential fatty acids on the thiol redox status of bovine mammary epithelia cells (BME-UV1) and their protective role against oxidative damage on the mammary gland by an in vitro study. The BME-UV1 cells were treated with complete medium containing 50 μM of cis-9,trans-11 CLA, trans-10,cis-12 CLA, α-linolenic acid, γ-linolenic acid, and linoleic acid. To assess the cellular antioxidant response, glutathione, NADPH, and γ-glutamyl-cysteine ligase activity were measured 48 h after addition of fatty acids (FA). Intracellular reactive oxygen species and malondialdehyde production were also assessed in cells supplemented with FA. Reactive oxygen species production after 3 h of H2O2 exposure was assessed to evaluate and to compare the potential protection of different FA against H2O2-induced oxidative stress. All FA treatments induced an intracellular GSH increase, matched by high concentrations of NADPH and an increase of γ-glutamyl-cysteine ligase activity. Cells supplemented with FA showed a reduction in intracellular malondialdehyde levels. In particular, CLA isomers and linoleic acid supplementation showed a better antioxidant cellular response against oxidative damage induced by H2O2 compared with other FA. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

  4. Old and New Stories: Revelations from Functional Analysis of the Bovine Mammary Transcriptome during the Lactation Cycle

    Science.gov (United States)

    Bionaz, Massimo; Periasamy, Kathiravan; Rodriguez-Zas, Sandra L.; Everts, Robin E.; Lewin, Harris A.; Hurley, Walter L.; Loor, Juan J.

    2012-01-01

    The cow mammary transcriptome was explored at −30, −15, 1, 15, 30, 60, 120, 240, and 300 d relative to parturition. A total of 6,382 differentially expressed genes (DEG) at a false discovery rate ≤0.001 were found throughout lactation. The greatest number of DEG (>3,500 DEG) was observed at 60 and 120 d vs. −30 d with the largest change between consecutive time points observed at −15 vs. 1 d and 120 vs. 240 d. Functional analysis of microarray data was performed using the Dynamic Impact Approach (DIA). The DIA analysis of KEGG pathways uncovered as the most impacted and induced ‘Galactose metabolism’, ‘Glycosylphosphatidylinositol (GPI)-anchor biosynthesis’, and ‘PPAR signaling’; whereas, ‘Antigen processing and presentation’ was among the most inhibited. The integrated interpretation of the results suggested an overall increase in metabolism during lactation, particularly synthesis of carbohydrates and lipid. A marked degree of utilization of amino acids as energy source, an increase of protein export, and a decrease of the protein synthesis machinery as well cell cycle also were suggested by the DIA analysis. The DIA analysis of Gene Ontology and other databases uncovered an induction of Golgi apparatus and angiogenesis, and the inhibition of both immune cell activity/migration and chromosome modifications during lactation. All of the highly-impacted and activated functions during lactation were evidently activated at the onset of lactation and inhibited when milk production declined. The overall analysis indicated that the bovine mammary gland relies heavily on a coordinated transcriptional regulation to begin and end lactation. The functional analysis using DIA underscored the importance of genes associated with lactose synthesis, lipid metabolism, protein synthesis, Golgi, transport, cell cycle/death, epigenetic regulation, angiogenesis, and immune function during lactation. PMID:22428004

  5. A mouse mammary gland involution mRNA signature identifies biological pathways potentially associated with breast cancer metastasis

    NARCIS (Netherlands)

    Stein, Torsten; Salomonis, Nathan; Nuyten, Dimitry S. A.; van de Vijver, Marc J.; Gusterson, Barry A.

    2009-01-01

    Mouse mammary gland involution resembles a wound healing response with suppressed inflammation. Wound healing and inflammation are also associated with tumour development, and a 'wound-healing' gene expression signature can predict metastasis formation and survival. Recent studies have shown that an

  6. Mammary analogue secretory carcinoma of salivary glands: a new entity associated with ETV6 gene rearrangement.

    Science.gov (United States)

    Majewska, Hanna; Skálová, Alena; Stodulski, Dominik; Klimková, Adéla; Steiner, Petr; Stankiewicz, Czesław; Biernat, Wojciech

    2015-03-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumour that harbours the recurrent ETV6-NTRK3 translocation. This is the first series of MASC cases identified in the historic cohort of carcinomas of salivary glands with clinical/pathological correlation and follow-up data. We reviewed 183 primary carcinomas of major and minor salivary glands resected at the Medical University of Gdańsk, Poland, between 1992 and 2012. Based on morphology and immunohistochemistry, cases suspicious for MASC were selected, and the diagnosis was confirmed by fluorescence in situ hybridization (FISH) for ETV6 rearrangement and by RT-PCR for the ETV6-NTRK3 fusion transcript. Seven carcinomas met the criteria of MASC, as they exhibited a typical appearance with solid/microcystic and papillary architecture and intraluminal secretions, and cells completely devoid of basophilic cytoplasmic zymogen granules indicative of true acinar differentiation. The only paediatric case was an unencapsulated tumour composed of macrocystic structures covered by a mostly single but, focally, double layer of cells with apocrine morphology. In all cases, the neoplastic cells revealed immunoreactivity for S100, mammaglobin, cytokeratin CK7, CK8, STAT5a and vimentin. FISH for ETV6 gene rearrangement was positive in six out of seven cases, and RT-PCR was positive in three cases. MASC is a new entity of malignant epithelial salivary gland tumours not included in the 2005 WHO Classification of Head and Neck Tumours. There is a growing body of evidence that it is not as rare as was assumed, as is also indicated by our series (3.8 %). In most cases, MASC shares some microscopic features with AciCC, adenocarcinoma/cystadenocarcinoma NOS and low-grade MEC. In rare cases, MASC with high-grade transformation may mimic the morphological appearances of high-grade salivary gland malignancies, such as salivary duct carcinoma.

  7. Mammary Analog Secretory Carcinoma (MASC) Involving the Thyroid Gland: A Report of the First 3 Cases.

    Science.gov (United States)

    Dettloff, Jennifer; Seethala, Raja R; Stevens, Todd M; Brandwein-Gensler, Margaret; Centeno, Barbara A; Otto, Kristen; Bridge, Julia A; Bishop, Justin A; Leon, Marino E

    2017-06-01

    Salivary gland-type tumors have been rarely described in the thyroid gland. Mammary Analog Secretory Carcinoma (MASC) is a recently defined type of salivary gland carcinoma characterized by a t(12;15)(p13;q25) resulting in an ETV6-NTRK3 fusion gene. We report 3 cases of MASC involving the thyroid gland without clinical evidence of a salivary gland or breast primary; the clinico-pathologic characteristics are reviewed. Assessment for rearrangement of the ETV6 (12p13) locus was conducted by fluorescence in situ hybridization (FISH) on representative FFPE sections using an ETV6 break apart probe (Abbott Molecular, Des Plaines, IL, USA). The patients were two females (52 and 55 years-old) and 1 male (74 years-old). The tumors were poorly circumscribed solid white tan nodules involving the thyroid. Histologically, they were invasive and showed solid, microcystic, cribriform, and tubular growth patterns composed of variably bland polygonal eosinophilic cells with vesicular nuclear chromatin and conspicuous nucleoli. All three cases showed metastasis to lymph nodes; one case showed lateral neck involvement. The tumor cells were positive for S100 and mammaglobin. GATA-3 and PAX-8 were positive in 2 cases, one of which only focally so. All three cases were negative for TTF-1 and thyroglobulin. Rearrangement of the ETV6 locus was confirmed in all cases and a diagnosis of MASC rendered for each case. A site of origin distinct from the thyroid gland was not identified, with a median follow up of 24 months. MASC may rarely involve the thyroid gland. The origin of these lesions is unknown; while an origin from ectopic salivary gland-type cells is entertained, a metastatic origin from an occult primary cannot be definitively excluded at this time. Given the histologic (follicular-like microcystic pattern with colloid-like secretions and papillary pattern), immunophenotypic (PAX-8), and even molecular overlap, MASC can be mistaken for papillary thyroid carcinoma and should be

  8. Inhibition of Staphylococcus aureus Invasion into Bovine Mammary Epithelial Cells by Contact with Live Lactobacillus casei

    Science.gov (United States)

    Bouchard, Damien S.; Rault, Lucie; Berkova, Nadia; Le Loir, Yves

    2013-01-01

    Staphylococcus aureus is a major pathogen that is responsible for mastitis in dairy herds. S. aureus mastitis is difficult to treat and prone to recurrence despite antibiotic treatment. The ability of S. aureus to invade bovine mammary epithelial cells (bMEC) is evoked to explain this chronicity. One sustainable alternative to treat or prevent mastitis is the use of lactic acid bacteria (LAB) as mammary probiotics. In this study, we tested the ability of Lactobacillus casei strains to prevent invasion of bMEC by two S. aureus bovine strains, RF122 and Newbould305, which reproducibly induce acute and moderate mastitis, respectively. L. casei strains affected adhesion and/or internalization of S. aureus in a strain-dependent manner. Interestingly, L. casei CIRM-BIA 667 reduced S. aureus Newbould305 and RF122 internalization by 60 to 80%, and this inhibition was confirmed for two other L. casei strains, including one isolated from bovine teat canal. The protective effect occurred without affecting bMEC morphology and viability. Once internalized, the fate of S. aureus was not affected by L. casei. It should be noted that L. casei was internalized at a low rate but survived in bMEC cells with a better efficiency than that of S. aureus RF122. Inhibition of S. aureus adhesion was maintained with heat-killed L. casei, whereas contact between live L. casei and S. aureus or bMEC was required to prevent S. aureus internalization. This first study of the antagonism of LAB toward S. aureus in a mammary context opens avenues for the development of novel control strategies against this major pathogen. PMID:23183972

  9. Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rat offspring.

    Science.gov (United States)

    Guido, Luiza N; Fontelles, Camile C; Rosim, Mariana P; Pires, Vanessa C; Cozzolino, Silvia M F; Castro, Inar A; Bolaños-Jiménez, Francisco; Barbisan, Luis F; Ong, Thomas P

    2016-10-15

    Breast cancer is a global public health problem and accumulating evidence indicates early-life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility. Male Sprague-Dawley rats were fed AIN93-G diet containing 0.15 ppm (control diet), 0.05 ppm (deficient diet) or 1 ppm (supplemented diet) of selenium for 9 weeks and mated with control female rats. Mammary carcinogenesis was induced with 7,12-dimethylbenz[a]anthracene (DMBA) in their female offspring. Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA-induced mammary tumors (increased incidence and higher grade tumors). On the other hand, paternal selenium supplementation did not influence any of these parameters. These results highlight the importance of father's nutrition including selenium status as a relevant factor affecting daughter's breast cancer risk and paternal preconception as a potential developmental stage to start disease preventive strategies. © 2016 UICC.

  10. Mammary gland immunology and neonate protection in pigs. Homing of lymphocytes into the MG.

    Science.gov (United States)

    Salmon, H

    2000-01-01

    Since placenta of pregnant sows are impermeable to immunoglobulin passage, the neonates are born agammaglobulinemic; although immunocompetent, they are unable to develop rapidly an immune response which will protect their systemic and mucosal compartments; thus their survival depend upon the passive acquisition of maternal immunity including at least 3 components: i) a systemic humoral immunity, transmitted through colostrum conveying mainly by IgG; these IgG are transferred from maternal serum via Fc gamma receptors on the epithelial cells of mammary gland (MG). ii) a local humoral immunity, especially secretory IgA (IgAs), transmitted mainly by milk (lactogenic immunity) until weaning. IgAs are secreted by MG recruited plasma cells and are excreted in milk via secretory component of epithelial cells: these IgA exhibit a specificity for the antigens present in the maternal digestive tract, the so-called "entero-mammary link"; this link is due to the migration of lymphocytes from the gut to the mammary gland; they are recruited from the blood via the interaction of their homing receptor (alpha 4 beta 7) with the developmentally regulated mucosal vascular addresin MadCAM-1. In the MG, MadCAM-1 increased in pregnancy (probably under oestrogenic stimulation) but regressed in lactation; its density is closely related to the T cell numbers in MG; in contrast the increase in plasma cell numbers is not related to MadCAM-1 density. Thus IgA precursor cells (alpha 4 beta 7 B cells) seem to be recruited by a milk B cell chemoattractant. On the other hand, presence of T and B lymphocytes in MG (some of them originating from the systemic compartment), sustains the attempts of MG immunization and the results sustain the view of a true local immune response. iii) possibly but not formally proved, a cellular immunity transmitted via maternal immunocompetent cells present in mammary secretions; the exported lymphocytes may represent a selected population of lymphocytes after their

  11. Extended immunologic and genetic lineage of mammary analogue secretory carcinoma of salivary glands.

    Science.gov (United States)

    Ni, Hao; Zhang, Xue-Ping; Wang, Xiao-Tong; Xia, Qiu-Yuan; Lv, Jing-Huan; Wang, Xuan; Shi, Shan-Shan; Li, Rui; Zhou, Xiao-Jun; Rao, Qiu

    2016-12-01

    Mammary analogue secretory carcinoma (MASC) of salivary glands is a newly recognized tumor entity. To explore a more practical and convenient immunohistochemical approach to distinguish MASC from other tumors arising from salivary glands as well as to expand the immunologic and genetic lineage of MASC, we examined 17 MASCs using clinicopathologic, immunohistochemical, and molecular analyses. Eighteen cases of acinic cell carcinoma, 18 cases of adenoid cystic carcinoma, 22 cases of mucoepidermoid carcinoma, and 14 cases of basal cell adenocarcinoma were brought in for comparison. Seventeen MASCs shared similar architectures with not only intraluminal or intracellular secretion but also low-grade vesicular nuclei. In addition, they were all immunoreactive for S-100 and SOX-10, whereas only 3 of 17 demonstrated reactivity for GATA-3 and P63, and 4 of 17 were focally positive for CD117. ETV6 translocation was detected in 10 cases by fluorescence in situ hybridization, whereas intact ETV6 was noted in 2 cases. Our data proposed a combined immunohistochemical panel to distinguish MASC from other tumors arising from salivary glands and expanded the immunologic and genetic lineage of MASC. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Aspiration cytology of mammary analogue secretory carcinoma of the salivary gland.

    Science.gov (United States)

    Jung, Min Jung; Kim, Sang Yoon; Nam, Soon Yuhl; Roh, Jong-Lyel; Choi, Seung-Ho; Lee, Jeong Hyun; Baek, Jung Hwan; Cho, Kyung-Ja

    2015-04-01

    Aspiration cytologic findings of mammary analogue secretory carcinoma (MASC), a newly established salivary gland neoplasm defined by a t(12;15)(p13;q25) ETV6-NTRK3 translocation, are not fully characterized to date. We report cytologic descriptions of nine cases of molecularly confirmed MASC, including two with unusual findings. Aspiration smears from nine MASCs of the salivary glands were retrospectively reviewed and analyzed according to the cellular and structural features of the corresponding surgical specimens. Aspiration smears of MASC generally reflected the histologic diversity of the tumors. Among usual histologic findings, a micropapillary pattern was associated with a predominance of vacuolated individual cells on aspiration smears, a papillary-cystic pattern with a predominance of thin branching papillary structures, and a microcystic pattern with a predominance of irregular sheets of eosinophilic cells. There were two unusual cases, one with three-dimensional groups of high-grade atypical cells, and one with epithelial clusters floating in a notably mucinous background. These cases represented MASC with high-grade transformation and MASC with cystadenocarcinoma-like features, respectively. The secretory activity of MASC was not prominent in the aspiration specimens. Although unusual cases were present, most MASC cases showed characteristic cytologic findings, which could aid the cytologic diagnosis of MASC. And knowledge of the histologic spectrum of MASC, including high-grade transformation, could be valuable for cytological differential diagnoses of salivary gland tumors, and the management of patients with MASC. © 2014 Wiley Periodicals, Inc.

  13. Finding and characterizing mammary analogue secretory carcinoma of the salivary gland.

    Science.gov (United States)

    Jung, Min Jung; Song, Joon Seon; Kim, Sang Yoon; Nam, Soon Yuhl; Roh, Jong-Lyel; Choi, Seung-Ho; Kim, Sung-Bae; Cho, Kyung-Ja

    2013-02-01

    A new tumor entity of the salivary glands, mammary analogue secretory carcinoma (MASC) with ETV6-NTRK3 translocation, has recently been proposed. MASC was originally diagnosed as adenocarcinoma, not otherwise specified (ANOS), or acinic cell carcinoma (AciCC) by the current World Health Organization classification. We aimed to identify MASC cases by molecular tests, and to characterize their clinical, histological, and immunohistochemical features. Thirty cases of MASC candidates were selected after review of 196 salivary gland tumors, and subjected to break-apart ETV6 fluorescence in situ hybridization (FISH), and immunohistochemical study for S100 protein, gross cystic disease fluid protein 15, DOG1, estrogen receptor, and progesterone receptor. Valid FISH results were obtained in 23 cases, and 13 positive cases were retrieved. MASCs were histologically varied, and the most frequent features observed in 10 cases were low-grade papillary/cystic/glandular patterns, intraluminal secretory materials, ovoid/wrinkled nuclei, and relatively abundant granular eosinophilic cytoplasms, corresponding to papillary-cystic or follicular types of AciCC. All cases showed diffuse immunopositivity for S100 protein. Three cases developed recurrences, but all patients remained alive. MASC could be a molecularly well-defined salivary gland neoplasm, encompassing some portions of AciCC and ANOS, but its histological spectrum and clinical implication require further investigation.

  14. Effect of stage of lactation on the immune competence of goat mammary gland.

    Science.gov (United States)

    Albenzio, M; Santillo, A; Caroprese, M; Ciliberti, M G; Marino, R; Sevi, A

    2016-05-01

    The present research was undertaken to evaluate the effect of stage of lactation on immune competence of the goat mammary gland. The prevalence and etiology of intramammary infections and cytokine pattern were studied in individual caprine milk during lactation. A total of 1,200 caprine milk samples were collected during early, mid, and late lactation (less than 40 d, from 110 to 130 d, and more than 200 d in lactation, respectively) and analyzed for milk quality, bacterial cell load, and cytokine pattern. Contagious and environmental pathogens associated with intramammary infection were isolated from caprine milk. Nutritional components of caprine milk were affected by stage of lactation; fat, protein, casein, and whey protein increased along with lactation due to the lowest milk yield. Lactose content showed an opposite trend, with a reduced percentage passing from early to late lactation. The impaired rheological properties detected in early and late lactation milk were associated with a modification of milk quality. An impairment of microbial quality was detected at the end of lactation as a consequence of a major susceptibility of mammary gland to infections. The percentage of bacteriologically positive caprine milk samples was 44% throughout lactation. The incidence of bacteria associated with intramammary infection was different according to the stage of lactation with a major prevalence of Staphylococcus aureus, Enterobacteriaceae, Staphylococcus hyicus, and Streptococcus uberis in early lactation milk, Staphylococcus chromogenes, Streptococcus bovis, and Staphylococcus epidermidis in mid lactation, and Pseudomonas aeruginosa and Staphylococcus caprae in late lactation milk. The higher values of IL-1β, tumor necrosis factor-α, and IL-6 were ascribed to the major prevalence of Staphylococcus aureus at the beginning of lactation, whereas a higher level of IL-10 was detected in mid-lactation caprine milk and correlated with Staphylococcus chromogenes

  15. Identification of novel and differentially expressed MicroRNAs of dairy goat mammary gland tissues using solexa sequencing and bioinformatics.

    Directory of Open Access Journals (Sweden)

    Zhibin Ji

    Full Text Available MicroRNAs are small, noncoding RNA molecules that regulate gene expression at the post-transcriptional level and play an important role in various biological processes. Although most microRNAs expression profiles studies have been performed in humans or rodents, relatively limited knowledge also exists in other mammalian species. The identification of the full repertoire of microRNAs expressed in the lactating mammary gland of Capra hircus would significantly increase our understanding of the physiology of lactating mammary glands. In this study, two libraries were constructed using the lactating mammary gland tissues of Laoshan dairy goats (Capra hircus during peak and late lactation. Solexa high-throughput sequencing technique and bioinformatics were used to determine the abundance and differential expression of the microRNAs between peak and late lactation. As a result, 19,044,002 and 7,385,833 clean reads were obtained, respectively, and 1,113 conserved known microRNAs and 31 potential novel microRNA candidates were identified. A total of 697 conserved microRNAs were significantly differentially expressed with a P-value<0.01, 272 microRNAs were up-regulated and 425 microRNAs were down-regulated during peak lactation. The results were validated using real-time quantitative RT-PCR. 762,557 annotated mRNA transcripts were predicted as putative target gene candidates. The GO annotation and KEGG pathway analysis suggested that differentially expressed microRNAs were involved in mammary gland physiology, including signal transduction, and cell-cell and cell-extracellular communications. This study provided the first global of the microRNA in Capra hircus and expanded the repertoire of microRNAs. Our results have great significance and value for the elucidation of complex regulatory networks between microRNAs and mRNAs and for the study of mammary gland physiology and lactation.

  16. Genetic control of ductal morphology, estrogen-induced ductal growth, and gene expression in female mouse mammary gland.

    Science.gov (United States)

    Wall, Emma H; Case, Laure K; Hewitt, Sylvia C; Nguyen-Vu, Trang; Candelaria, Nicholes R; Teuscher, Cory; Lin, Chin-Yo

    2014-08-01

    The uterotropic response of the uterus to 17β-estradiol (E2) is genetically controlled, with marked variation observed depending on the mouse strain studied. Previous genetic studies from our laboratory using inbred mice that are high (C57BL6/J; B6) or low (C3H/HeJ; C3H) responders to E2 led to the identification of quantitative trait loci (QTL) associated with phenotypic variation in uterine growth and leukocyte infiltration. Like the uterus, phenotypic variation in the responsiveness of the mammary gland to E2 during both normal and pathologic conditions has been reported. In the current experiment, we utilized an E2-specific model of mammary ductal growth combined with a microarray approach to determine the degree to which genotype influences the responsiveness of the mammary gland to E2, including the associated transcriptional programs, in B6 and C3H mice. Our results reveal that E2-induced mammary ductal growth and ductal morphology are genetically controlled. In addition, we observed a paradoxical effect of mammary ductal growth in response to E2 compared with what has been reported for the uterus; B6 is a high responder for the uterus and was a low responder for mammary ductal growth, whereas the reverse was observed for C3H. In contrast, B6 was a high responder for mammary ductal side branching. The B6 phenotype was associated with increased mammary epithelial cell proliferation and apoptosis, and a distinct E2-induced transcriptional program. These findings lay the groundwork for future experiments designed to investigate the genes and mechanisms underlying phenotypic variation in tissue-specific sensitivity to systemic and environmental estrogens during various physiological and disease states.

  17. The ABCG2 Efflux Transporter in the Mammary Gland Mediates Veterinary Drug Secretion across the Blood-Milk Barrier into Milk of Dairy Cows.

    Science.gov (United States)

    Mahnke, Hanna; Ballent, Mariana; Baumann, Sven; Imperiale, Fernanda; von Bergen, Martin; Lanusse, Carlos; Lifschitz, Adrian L; Honscha, Walther; Halwachs, Sandra

    2016-05-01

    In human and mice ATP-binding cassette efflux transporter ABCG2 represents the main route for active drug transport into milk. However, there is no detailed information on the role of ABCG2 in drug secretion and accumulation in milk of dairy animals. We therefore examined ABCG2-mediated drug transport in the bovine mammary gland by parallel pharmacokinetic studies in lactating Jersey cows and in vitro flux studies using the anthelmintic drug monepantel (MNP) as representative bovine ABCG2 (bABCG2) drug substrate. Animals received MNP (Zolvix, Novartis Animal Health Inc.) once (2.5 mg/kg per os) and the concentrations of MNP and the active MNP metabolite MNPSO2 were assessed by high-performance liquid chromatography. Compared with the parent drug MNP, we detected higher MNPSO2 plasma concentrations (expressed as area under the concentration-versus-time curve). Moreover, we observed MNPSO2 excretion into milk of dairy cows with a high milk-to-plasma ratio of 6.75. In mechanistic flux assays, we determined a preferential time-dependent basolateral-to-apical (B > A) MNPSO2 transport across polarized Madin-Darby canine kidney II cells-bABCG2 monolayers using liquid chromatography coupled with tandem mass spectrometry analysis. The B > A MNPSO2 transport was significantly inhibited by the ABCG2 inhibitor fumitremorgin C in bABCG2- but not in mock-transduced MDCKII cells. Additionally, the antibiotic drug enrofloxacin, the benzimidazole anthelmintic oxfendazole and the macrocyclic lactone anthelmintic moxidectin caused a reduction in the MNPSO2(B > A) net efflux. Altogether, this study indicated that therapeutically relevant drugs like the anthelmintic MNP represent substrates of the bovine mammary ABCG2 transporter and may thereby be actively concentrated in dairy milk. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  18. The role of mast cell in tissue morphogenesis. Thymus, duodenum, and mammary gland as examples.

    Science.gov (United States)

    Ribatti, Domenico; Crivellato, Enrico

    2016-02-01

    Mast cells (MCs) are strategically located at host/environment interfaces like skin, airways, and gastro-intestinal and uro-genital tracts. MCs also populate connective tissues in association with blood and lymphatic vessels and nerves. MCs are absent in avascular tissues, such as mineralized bone, cartilage, and cornea. MCs have various functions and different functional subsets of MCs are encountered in different tissues. However, we do not' know exactly what is the physiological function of MC. Most of these functions are not essential for life, as various MC-deficient strains of mice and rats seems to have normal life spans. In this review article, we have reported and discussed the literature data concerning the role of MCs in tissue morphogenesis, and in particular their role in the development of thymus, duodenum, and mammary gland. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Aluminium chloride promotes tumorigenesis and metastasis in normal murine mammary gland epithelial cells.

    Science.gov (United States)

    Mandriota, Stefano J; Tenan, Mirna; Ferrari, Paolo; Sappino, André-Pascal

    2016-12-15

    Aluminium salts, present in many industrial products of frequent use like antiperspirants, anti-acid drugs, food additives and vaccines, have been incriminated in contributing to the rise in breast cancer incidence in Western societies. However, current experimental evidence supporting this hypothesis is limited. For example, no experimental evidence that aluminium promotes tumorigenesis in cultured mammary epithelial cells exists. We report here that long-term exposure to concentrations of aluminium-in the form of aluminium chloride (AlCl3 )-in the range of those measured in the human breast, transform normal murine mammary gland (NMuMG) epithelial cells in vitro as revealed by the soft agar assay. Subcutaneous injections into three different mouse strains with decreasing immunodeficiency, namely, NOD SCID gamma (NSG), NOD SCID or nude mice, revealed that untreated NMuMG cells form tumors and metastasize, to a limited extent, in the highly immunodeficient and natural killer (NK) cell deficient NSG strain, but not in the less permissive and NK cell competent NOD SCID or nude strains. In contrast, NMuMG cells transformed in vitro by AlCl3 form large tumors and metastasize in all three mouse models. These effects correlate with a mutagenic activity of AlCl3 . Our findings demonstrate for the first time that concentrations of aluminium in the range of those measured in the human breast fully transform cultured mammary epithelial cells, thus enabling them to form tumors and metastasize in well-established mouse cancer models. Our observations provide experimental evidence that aluminium salts could be environmental breast carcinogens. © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

  20. Mammary extracellular matrix directs differentiation of testicular and embryonic stem cells to form functional mammary glands in vivo.

    Science.gov (United States)

    Bruno, Robert D; Fleming, Jodie M; George, Andrea L; Boulanger, Corinne A; Schedin, Pepper; Smith, Gilbert H

    2017-01-10

    Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived cells to produce normal mammary epithelial trees within epithelial divested mouse mammary fat-pads. Conversely, ECMs isolated from omental fat and lung did not redirect testicular cells to a MEC fate, indicating the necessity of tissue specific components of the mECM. mECM preparations also completely inhibited teratoma formation from ESC inoculations. Further, a phenotypically normal ductal outgrowth resulted from a single inoculation of ESCs and mECM. To the best of our knowledge, this is the first demonstration of a tissue specific ECM driving differentiation of cells to form a functional tissue in vivo.

  1. Modeling the effect of energy status on mammary gland growth and lactation.

    Science.gov (United States)

    Vetharaniam, I; Davis, S R; Upsdell, M; Kolver, E S; Pleasants, A B

    2003-10-01

    The impact of nutrition on lactation can be separated into acute effects, affecting day-to-day yield, and chronic effects, which govern the persistency of lactation and rate of decline of the lactation curve. A mathematical model of the mammary gland was constructed to investigate both acute and chronic effects. Mammary growth is expressed in terms of the dynamics of populations of active (secreting) and quiescent (engorged) alveoli. The secretion rate of active alveoli is expressed in terms of the energy status of the dam. The model was fitted to data from a 2 x 2 factorial trial in which lactation curves were measured for heifers of two different genotypes (North American and New Zealand Holstein-Friesians) fed two different diets [grass and total mixed rations (TMR)]. Total formation of alveoli during pregnancy and lactation was statistically the same across all groups despite differences between diets, in the rate of formation of alveoli at parturition. The senescence rate of alveoli was significantly higher for heifers fed grass compared with heifers fed TMR, which corresponds to better persistency for heifers fed TMR. Heifers fed TMR had a higher rate of reactivation of quiescent alveoli than heifers fed grass, which also contributes to increased persistence for heifers fed TMR. There was a genotype x diet interaction in the rate of quiescence of active alveoli: the North American-Grass group had a higher rate of quiescence than the other three groups, perhaps reflecting differences in selection pressures between the New Zealand and North American genotypes.

  2. HISTOLOGICAL STUDY OF HUMAN MAMMARY GLAND IN WOMEN OF NORTH EASTERN REGION OF INDIA

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    Santona

    2015-09-01

    Full Text Available INTRODUCTION: The “mamma” or “breast” is a modified, ectodermal, glandular structure located in the superficial fascia of the anterior chest wall. In female they are evolved to secrete milk for the nourishment of their offspring. They are also present in a rudimentary form in males. MATERIALS AND METHODS: After obtaining institutional ethical clearance t he specimens of human mammary gland were divided into two groups i.e. reproductive (14 to 49 and post - menopausal (50 and above age. The specimens of both the age group were collected from fresh unembalmed human cadaver. The slides were prepared using the standard laboratory procedure. Stained slides were studied for different structures of the mammary gland such as the glandular structures, ducts and myoepithelial cells. Diameters of the ducts were measured in both age groups. The data were analyzed to ca lculate the mean and ‘t’ test was applied to find out the significant difference between mean values. RESULTS: The average diameter of the lactiferous duct as measured by micrometer scale was 2.0 mm and 0.83 mm in reproductive and post - menopausal age group respectively. Calculated value of t’= 4.68. d. f. (degree of freedom =18, P <0.01. Therefore the diameter of lactiferous duct between reproductive and postmenopausal age group differs significantly. DISCUSSION: The results obtained in this study are comp ared with the available established findings of other workers to draw a definite conclusion in the histomorphological aspect of reproductive and postmenopausal age group. CONCLUSION: Though different generations of sophisticated investigations such as mole cular level studies have evolved for the early detection of breast carcinoma, the knowledge of the normal developmental histological changes is most important which will help to detect early abnormal changes of the breast if any

  3. Immunohistochemical evidence of rapid extracellular matrix remodeling after iron-particle irradiation of mouse mammary gland

    Science.gov (United States)

    Ehrhart, E. J.; Gillette, E. L.; Barcellos-Hoff, M. H.; Chaterjee, A. (Principal Investigator)

    1996-01-01

    High-LET radiation has unique physical and biological properties compared to sparsely ionizing radiation. Recent studies demonstrate that sparsely ionizing radiation rapidly alters the pattern of extracellular matrix expression in several tissues, but little is known about the effect of heavy-ion radiation. This study investigates densely ionizing radiation-induced changes in extracellular matrix localization in the mammary glands of adult female BALB/c mice after whole-body irradiation with 0.8 Gy 600 MeV iron particles. The basement membrane and interstitial extracellular matrix proteins of the mammary gland stroma were mapped with respect to time postirradiation using immunofluorescence. Collagen III was induced in the adipose stroma within 1 day, continued to increase through day 9 and was resolved by day 14. Immunoreactive tenascin was induced in the epithelium by day 1, was evident at the epithelial-stromal interface by day 5-9 and persisted as a condensed layer beneath the basement membrane through day 14. These findings parallel similar changes induced by gamma irradiation but demonstrate different onset and chronicity. In contrast, the integrity of epithelial basement membrane, which was unaffected by sparsely ionizing radiation, was disrupted by iron-particle irradiation. Laminin immunoreactivity was mildly irregular at 1 h postirradiation and showed discontinuities and thickening from days 1 to 9. Continuity was restored by day 14. Thus high-LET radiation, like sparsely ionizing radiation, induces rapid-remodeling of the stromal extracellular matrix but also appears to alter the integrity of the epithelial basement membrane, which is an important regulator of epithelial cell proliferation and differentiation.

  4. Dissecting the dynamics of dysregulation of cellular processes in mouse mammary gland tumor

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    de la Fuente Alberto

    2009-12-01

    Full Text Available Abstract Background Elucidating the sequence of molecular events underlying breast cancer formation is of enormous value for understanding this disease and for design of an effective treatment. Gene expression measurements have enabled the study of transcriptome-wide changes involved in tumorigenesis. This usually occurs through identification of differentially expressed genes or pathways. Results We propose a novel approach that is able to delineate new cancer-related cellular processes and the nature of their involvement in tumorigenesis. First, we define modules as densely interconnected and functionally enriched areas of a Protein Interaction Network. Second, 'differential expression' and 'differential co-expression' analyses are applied to the genes in these network modules, allowing for identification of processes that are up- or down-regulated, as well as processes disrupted (low co-expression or invoked (high co-expression in different tumor stages. Finally, we propose a strategy to identify regulatory miRNAs potentially responsible for the observed changes in module activities. We demonstrate the potential of this analysis on expression data from a mouse model of mammary gland tumor, monitored over three stages of tumorigenesis. Network modules enriched in adhesion and metabolic processes were found to be inactivated in tumor cells through the combination of dysregulation and down-regulation, whereas the activation of the integrin complex and immune system response modules is achieved through increased co-regulation and up-regulation. Additionally, we confirmed a known miRNA involved in mammary gland tumorigenesis, and present several new candidates for this function. Conclusions Understanding complex diseases requires studying them by integrative approaches that combine data sources and different analysis methods. The integration of methods and data sources proposed here yields a sensitive tool, able to pinpoint new processes with a

  5. Antibody-Guided In Vivo Imaging for Early Detection of Mammary Gland Tumors

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    Laura Jeffords Moore

    2016-08-01

    Full Text Available BACKGROUND: Earlier detection of transformed cells using target-specific imaging techniques holds great promise. We have developed TAB 004, a monoclonal antibody highly specific to a protein sequence accessible in the tumor form of MUC1 (tMUC1. We present data assessing both the specificity and sensitivity of TAB 004 in vitro and in genetically engineered mice in vivo. METHODS: Polyoma Middle T Antigen mice were crossed to the human MUC1.Tg mice to generate MMT mice. In MMT mice, mammary gland hyperplasia is observed between 6 and 10 weeks of age that progresses to ductal carcinoma in situ by 12 to 14 weeks and adenocarcinoma by 18 to 24 weeks. Approximately 40% of these mice develop metastasis to the lung and other organs with a tumor evolution that closely mimics human breast cancer progression. Tumor progression was monitored in MMT mice (from ages 8 to 22 weeks by in vivo imaging following retro-orbital injections of the TAB 004 conjugated to indocyanine green (TAB-ICG. At euthanasia, mammary gland tumors and normal epithelial tissues were collected for further analyses. RESULTS: In vivo imaging following TAB-ICG injection permitted significantly earlier detection of tumors compared with physical examination. Furthermore, TAB-ICG administration in MMT mice enabled the detection of lung metastases while sparing recognition of normal epithelia. CONCLUSIONS: The data highlight the specificity and the sensitivity of the TAB 004 antibody in differentiating normal versus tumor form of MUC1 and its utility as a targeted imaging agent for early detection, tumor monitoring response, as well as potential clinical use for targeted drug delivery.

  6. Pathology of Staphylococcus aureus mastitis during lactogenesis: relationships with bovine mammary structure and function.

    Science.gov (United States)

    Sordillo, L M; Nickerson, S C; Akers, R M

    1989-01-01

    Pathological alterations of mammary parenchymal tissue from 5 dairy cows with Staphylococcus aureus mastitis were studied. Tissue from infected quarters exhibited less synthetic and secretory ability during lactogenesis, as indicated by lower percentages of luminal area, but higher percentages of stromal area compared with control tissue. Ultrastructural analysis of alveolar epithelium demonstrated decreased numbers of organelles associated with milk synthesis and secretion. Mammary secretion from 12 additional cows confirmed the loss of secretory potential in infected quarters as concentrations of alpha-lactalbumin were lower during the first 14 d of lactation compared with concentrations from controls. Higher concentrations of serum alpha-lactalbumin from cows with Staphylococcus aureus mastitis suggest leakage of mammary secretion through gaps left by damaged or sloughed alveolar epithelium. Macrophages and lymphocytes were observed frequently in large gaps between basal plasma membrane of secretory cells and the basal lamina which may contribute to epithelial damage. Ability of neutrophils and macrophages to phagocytize staphylococci may have been compromised in the prelactating gland due to the indiscriminate ingestion of accumulated fat and casein.

  7. Overexpression of aromatase in transgenic male mice results in the induction of gynecomastia and other biochemical changes in mammary glands.

    Science.gov (United States)

    Gill, K; Kirma, N; Tekmal, R R

    2001-04-01

    Our previous studies have shown that overexpression of aromatase in mammary glands results in the induction of hyperplastic and dysplastic changes in female transgenic mice. In this study we show that overexpression of aromatase in male transgenic mice results in increased mammary growth and histopathological changes similar to gynecomastia. Increased estrogenic activity also results in an increase in estrogen and progesterone receptor expression in the mammary glands of transgenic males as compared to the nontransgenic males, as well as an increase in the expression of various genes involved in cell cycle and cell proliferation. We have also observed an increase in certain growth factors, such as bFGF and TGFbeta, as a result of aromatase overexpression in the male transgenic mammary glands. In order to obtain a better understanding of the biological significance of gynecomastia, a reliable model is necessary to explain the mechanisms and correlations associated with human cancers. This model, can potentially serve as a predictable and useful tool for studying gynecomastia, hormonal carcinogenesis and action of other carcinogens on hormone induced cancers.

  8. Methionine Induces LAT1 Expression in Dairy Cow Mammary Gland by Activating the mTORC1 Signaling Pathway.

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    Duan, Xiaoyu; Lin, Ye; Lv, He; Yang, Yang; Jiao, Hongtao; Hou, Xiaoming

    2017-12-01

    Methionine is the limiting amino acid for milk protein synthesis in dairy cows. The effect of methionine availability on milk protein synthesis is dependent on its active transport into cells through amino acid transporters. L-type amino acid transporter 1 (LAT1), which induces the transport of neutral amino acids, is highly expressed in lactating mammary gland. However, the effect of methionine on LAT1 expression and the mechanism governing this process in dairy cow mammary gland are poorly understood. In this study, we show that treatment of dairy cow mammary epithelial cells with increasing concentrations of methionine for 24 h resulted in increased expression of LAT1 and its associated protein 4F2 heavy chain (4F2hc). Maximal expression levels occurred after treatment with 0.6 mM methionine. Methionine treatment also increased cell viability and β-casein synthesis. Western blots showed that methionine induced LAT1 and 4F2hc expression by activating mammalian target of rapamycin complex 1 (mTORC1) signaling. Inhibition of mTORC1 signaling by rapamycin or raptor siRNA prevented the upregulation of LAT1 and 4F2hc. These results indicate that methionine may activate the mTORC1 signaling pathway and further increase LAT1 and 4F2hc expression in dairy cow mammary gland, thus affecting milk protein synthesis.

  9. Adeno-associated-virus-mediated transduction of the mammary gland enables sustained production of recombinant proteins in milk.

    Science.gov (United States)

    Wagner, Stefan; Thresher, Rosemary; Bland, Ross; Laible, Götz

    2015-10-14

    Biopharming for the production of recombinant pharmaceutical proteins in the mammary gland of transgenic animals is an attractive but laborious alternative compared to mammalian cell fermentation. The disadvantage of the lengthy process of genetically modifying an entire animal could be circumvented with somatic transduction of only the mammary epithelium with recombinant, replication-defective viruses. While other viral vectors offer very limited scope for this approach, vectors based on adeno-associated virus (AAV) appear to be ideal candidates because AAV is helper-dependent, does not induce a strong immune response and has no association with disease. Here, we sought to test the suitability of recombinant AAV (rAAV) for biopharming. Using reporter genes, we showed that injected rAAV efficiently transduced mouse mammary cells. When rAAV encoding human myelin basic protein (hMBP) was injected into the mammary glands of mice and rabbits, this resulted in the expression of readily detectable protein levels of up to 0.5 g/L in the milk. Furthermore we demonstrated that production of hMBP persisted over extended periods and that protein expression could be renewed in a subsequent lactation by re-injection of rAAV into a previously injected mouse gland.

  10. Chemerin is a novel regulator of lactogenesis in bovine mammary epithelial cells.

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    Suzuki, Yutaka; Haga, Satoshi; Katoh, Daiki; So, Kyoung-ha; Choi, Ki-choon; Jung, U-suk; Lee, Hong-gu; Katoh, Kazuo; Roh, Sang-gun

    2015-10-23

    Chemerin is a chemoattractant cytokine (chemokine) produced by adipocytes and hepatocytes; it regulates insulin sensitivity and adipocyte differentiation. The objective of this study was to investigate the effect of chemerin on the expression of genes related to lactogenesis and the regulators of chemerin signaling in a bovine mammary epithelial cell line (MAC-T). Two types of chemerin receptors, chemokine like-receptor 1 (CMKLR1) and chemokine (C-C motif) receptor-like 2 (CCRL2), were detected in cultured MAC-T cells, whereas chemerin was not detected. G protein-coupled receptor 1 (GPR1), another receptor of chemerin, was undetectable in MAC-T cells. Chemerin upregulated transcript expression of CMKLR1, CCRL2, and genes associated with fatty acid synthesis, glucose uptake, insulin signaling, and casein synthesis in MAC-T cells. Lactogenic hormones (insulin, growth hormone, and prolactin) downregulated the expression of CMKLR1 in MAC-T cells. Adiponectin suppressed CMKLR1 expression. TNF-α suppressed CMKLR1, but induced CCRL2 expression. These data suggest chemerin is a novel regulator of lactogenesis via its own receptor in bovine mammary epithelial cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Expression of NGF, BDNF and their high-affinity receptors in ovine mammary glands during development and lactation.

    Science.gov (United States)

    Colitti, Monica

    2015-12-01

    The distribution of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and their high-affinity tyrosine kinase receptors TrkA and TrkB was investigated by immunohistochemical method in the mammary gland of ewes from prepubertal stage to involution. NGF and BDNF protein expressions were strong during development of glands at prepubertal stage and during pregnancy and decreased during lactation and involution. The expressions localized in both stromal and parenchymal cells of developing gland were mainly arranged in the apical side of secretory cells during lactation. These observations were also confirmed at transcriptional level by RT-PCR analyses. The highest expression of all genes significantly occurred at prepubertal stage. NGF was then down-regulated from pregnancy to involution, and no statistical differences were observed among these stages. The receptor TrkA was also under-expressed from pregnancy to involution, and its expression significantly differed between pregnancy and 30 days of lactation and also between 30 and 60 days of lactation. BDNF was significantly down-regulated at 60 days of lactation in comparison with prepubertal stage and again between pregnancy and 30 days of lactation. The relative abundance of its receptor, TrkB, showed also a significant down-regulation at 60 days of lactation in comparison with pregnancy and involution. Among the myriad of other molecular signals involved in the mammary gland cycle, the local production of neuropeptides and their receptors could be of interest in understanding their potential role in mammary biology.

  12. Miz1 Deficiency in the Mammary Gland Causes a Lactation Defect by Attenuated Stat5 Expression and Phosphorylation

    Science.gov (United States)

    Sanz-Moreno, Adrián; Fuhrmann, David; Wolf, Elmar; von Eyss, Björn; Eilers, Martin; Elsässer, Hans-Peter

    2014-01-01

    Miz1 is a zinc finger transcription factor with an N-terminal POZ domain. Complexes with Myc, Bcl-6 or Gfi-1 repress expression of genes like Cdkn2b (p15Ink4) or Cdkn1a (p21Cip1). The role of Miz1 in normal mammary gland development has not been addressed so far. Conditional knockout of the Miz1 POZ domain in luminal cells during pregnancy caused a lactation defect with a transient reduction of glandular tissue, reduced proliferation and attenuated differentiation. This was recapitulated in vitro using mouse mammary gland derived HC11 cells. Further analysis revealed decreased Stat5 activity in Miz1ΔPOZ mammary glands and an attenuated expression of Stat5 targets. Gene expression of the Prolactin receptor (PrlR) and ErbB4, both critical for Stat5 phosphorylation (pStat5) or pStat5 nuclear translocation, was decreased in Miz1ΔPOZ females. Microarray, ChIP-Seq and gene set enrichment analysis revealed a down-regulation of Miz1 target genes being involved in vesicular transport processes. Our data suggest that deranged intracellular transport and localization of PrlR and ErbB4 disrupt the Stat5 signalling pathway in mutant glands and cause the observed lactation phenotype. PMID:24586582

  13. Mammary analogue secretory carcinoma of salivary glands: diagnostic pitfall with distinct immunohistochemical profile and molecular features.

    Science.gov (United States)

    Bissinger, Oliver; Götz, Carolin; Kolk, Andreas; Bier, Henning A; Agaimy, Abbas; Frenzel, Henning; Perner, Sven; Ribbat-Idel, Julika; Wolff, Klaus Dietrich; Weichert, Wilko; Mogler, Caroline

    2017-10-03

    Mammary analogue secretory carcinoma (MASC) is a newly defined entity among salivary gland malignancies which has just been established in the 4(th) edition of the WHO classification of head and neck tumors. MASC (synonym: secretory carcinoma) are characterized by a specific rearangement of the ETV6 gene locus. Here, we present a series of 3 MASC cases including clinical data with follow-up for up to 26 months. All tumours immunhistochemically displayed strong positivity for cytokeratin 7, and mammaglobin, focal positivity for S100, cytokeratin 5/6 and muc-4. In contrast, immunhistochemical stainings against cytokeratin 14, hormon receptors, Her2/neu, androgen receptor and prostate-specific antigen were consistently negative. FISH analysis showed translocation of the ETV6 gene locus in the majority of tumour cell nuclei. During clinical follow-up, no local relapse or metastasis was detected. As these carcinomas are clinically and radiologically indistinguishable from other salivary gland tumours and as therapeutic approaches and prognosis might differ, we need to be able to diagnose MASC correctly.

  14. Mammary analog secretory carcinoma of the parotid gland: A case report and literature review.

    Science.gov (United States)

    Balanzá, Ricardo; Arrangoiz, Rodrigo; Cordera, Fernando; Muñoz, Manuel; Luque-de-León, Enrique; Moreno, Eduardo; Toledo, Carlos; González, Edgar

    2015-01-01

    Background Mammary analog secretory carcinoma (MASC) was first described in 2010 by Skálová et al. This entity shares morphologic and immunohistochemical features with the secretory carcinoma (SC) of the breast. MASC usually presents as an asymptomatic mass in the parotid gland and predominantly affects men. This tumor is considered a low-grade carcinoma but has the potential for high-grade transformation. We report one MASC case and a review of world literature. Case report A 66-year-old male patient presented because he noticed a mass of approximately 3 × 3 cm on the right pre-auricular region. Physical examination demonstrated a 3 × 3.5 cm, firm, fixed, non-tender mass in the right pre-auricular region. An MRI of the head and neck showed an ovoid heterogeneous lesion, dependent of the right parotid gland of 27 × 28 mm. We performed a superficial parotidectomy with identification and preservation of the facial nerve. The immunophenotype was positive for epithelial membrane antigen (EMA), CK8/18, vimentin, S-100 protein, and mammoglobin. No further surgical interventions or adjuvant therapies were needed. The patient will have a close follow up. Conclusion The presence of t(12;15) (p13;q25) translocation which results in the ETV6-NTRK3 gene fusion or positive immunochemical studies for STAT5, mammoglobin and S100 protein, are necessary to confirm the diagnosis of MASC. MASC treatment should mimic the management of other low-grade malignant salivary gland neoplasms. The inhibition of ETV6-NTRK3 gene fusion could be used as treatment in the future. PMID:26496413

  15. Intramammary Immunization of Pregnant Mice with Staphylococcal Protein A Reduces the Post-Challenge Mammary Gland Bacterial Load but Not Pathology.

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    Jully Gogoi-Tiwari

    Full Text Available Protein A, encoded by the spa gene, is one of the major immune evading MSCRAMM of S. aureus, demonstrated to be prevalent in a significant percentage of clinical bovine mastitis isolates in Australia. Given its' reported significance in biofilm formation and the superior performance of S. aureus biofilm versus planktonic vaccine in the mouse mastitis model, it was of interest to determine the immunogenicity and protective potential of Protein A as a potential vaccine candidate against bovine mastitis using the mouse mastitis model. Pregnant Balb/c mice were immunised with Protein A emulsified in an alum-based adjuvant by subcutaneous (s/c or intramammary (i/mam routes. While humoral immune response of mice post-immunization were determined using indirect ELISA, cell-mediated immune response was assessed by estimation of interferon-gamma (IFN-γ produced by protein A-stimulated splenocyte supernatants. Protective potential of Protein A against experimental mastitis was determined by challenge of immunized versus sham-vaccinated mice by i/mam route, based upon manifestation of clinical symptoms, total bacterial load and histopathological damage to mammary glands. Significantly (p<0.05 higher levels of IgG1 isotype were produced in mice immunized by the s/c route. In contrast, significantly higher levels of the antibody isotype IgG2a were produced in mice immunized by the i/mam route (p<0.05. There was significant reduction (p<0.05 in bacterial loads of the mammary glands of mice immunized by Protein A regardless of the route of immunization, with medium level of clinical symptoms observed up to day 3 post-challenge. However, Protein A vaccine failed to protect immunized mice post-challenge with biofilm producing encapsulated S. aureus via i/mam route, regardless of the route of immunization, as measured by the level of mammary tissue damage. It was concluded that, Protein A in its' native state was apparently not a suitable candidate for inclusion

  16. DNA adducts from nitroreduction of 2,7-dinitrofluorene, a mammary gland carcinogen, catalyzed by rat liver or mammary gland cytosol.

    Science.gov (United States)

    Ritter, Clare L; Culp, Sandra J; Freeman, James P; Marques, M Matilde; Beland, Frederick A; Malejka-Giganti, Danuta

    2002-04-01

    cytosol with acetyl CoA yielded two adducts (>2/10(6) nucleotides). Differences in the TLC migration of these adducts, compared to those from 2,7-diNF, and the lack of 2,7-diNF formation in the incubations suggested retention of the C9-oxidized groups. The relative ratios of the amine to amide from nitroreductions of 9-oxo-2,7-diNF and 2,7-diNF catalyzed by liver cytosol suggested that the 9-oxo group decreased reactivity with acyltransferase and, thus, the amount of N-acetoxy arylamine that binds to DNA. The mammary gland tumorigenicity of 2,7-diNF and the extent of its activation by the tumor target tissue shown herein suggest relevance of this environmental pollutant for breast cancer.

  17. Involvement of Different networks in mammary gland involution after the pregnancy/lactation cycle: Implications in breast cancer.

    Science.gov (United States)

    Zaragozá, Rosa; García-Trevijano, Elena R; Lluch, Ana; Ribas, Gloria; Viña, Juan R

    2015-04-01

    Early pregnancy is associated with a reduction in a woman's lifetime risk for breast cancer. However, different studies have demonstrated an increase in breast cancer risk in the years immediately following pregnancy. Early and long-term risk is even higher if the mother age is above 35 years at the time of first parity. The proinflammatory microenvironment within the mammary gland after pregnancy renders an "ideal niche" for oncogenic events. Signaling pathways involved in programmed cell death and tissue remodeling during involution are also activated in breast cancer. Herein, the major signaling pathways involved in mammary gland involution, signal transducer and activator of transcription (STAT3), nuclear factor-kappa B (NF-κB), transforming growth factor beta (TGFβ), and retinoid acid receptors (RARs)/retinoid X receptors (RXRs), are reviewed as part of the complex network of signaling pathways that crosstalk in a contextual-dependent manner. These factors, also involved in breast cancer development, are important regulatory nodes for signaling amplification after weaning. Indeed, during involution, p65/p300 target genes such as MMP9, Capn1, and Capn2 are upregulated. Elevated expression and activities of these proteases in breast cancer have been extensively documented. The role of these proteases during mammary gland involution is further discussed. MMPs, calpains, and cathepsins exert their effect by modification of the extracellular matrix and intracellular proteins. Calpains, activated in the mammary gland during involution, cleave several proteins located in cell membrane, lysosomes, mitochondria, and nuclei favoring cell death. Besides, during this period, Capn1 is most probably involved in the modulation of preadipocyte differentiation through chromatin remodeling. Calpains can be implicated in cell anchoring loss, providing a proper microenvironment for tumor growth. A better understanding of the role of any of these proteases in tumorigenesis may

  18. Escherichia coli infection induces distinct local and systemic transcriptome responses in the mammary gland

    Directory of Open Access Journals (Sweden)

    Wolf Eckhard

    2010-02-01

    Full Text Available Abstract Background Coliform bacteria are the most common etiologic agents in severe mastitis of cows. Escherichia coli infections are mostly restricted to a single udder quarter whereas neighboring quarters stay clinically inapparent, implicating the presence of a systemic defense reaction. To address its underlying mechanism, we performed a transcriptome study of mammary tissue from udder quarters inoculated with E. coli (6 h and 24 h post infection, from neighboring quarters of the same animals, and from untreated control animals. Results After 6 h 13 probe sets of differentially expressed genes (DEG were detected in infected quarters versus control animals. Eighteen hours later 2154 and 476 DEG were found in infected and in neighboring quarters vs. control animals. Cluster analysis revealed DEG found only in infected quarters (local response and DEG detected in both infected and neighboring quarters (systemic response. The first group includes genes mainly involved in immune response and inflammation, while the systemic reaction comprises antigen processing and presentation, cytokines, protein degradation and apoptosis. Enhanced expression of antimicrobial genes (S100A8, S100A9, S100A12, CXCL2, GNLY, acute phase genes (LBP, SAA3, CP, BF, C6, C4BPA, IF, and indicators of oxidative stress (GPX3, MT1A, MT2A, SOD2 point to an active defense reaction in infected and neighboring healthy quarters. Its early onset is indicated by increased transcription of NFIL3 at 6 h. NFIL3 is a predicted regulator of many genes of the systemic response at 24 h. The significance of our transcriptome study was evidenced by some recent findings with candidate gene based approaches. Conclusions The discovery and holistic analysis of an extensive systemic reaction in the mammary gland significantly expands the knowledge of host-pathogen interactions in mastitis which may be relevant for the development of novel therapies and for genetic selection towards mastitis

  19. The Biology of Progesterone Receptor in the Normal Mammary gland and in Breast Cancer

    Science.gov (United States)

    Obr, Alison; Edwards, Dean P.

    2011-01-01

    This paper reviews work on progesterone and the progesterone receptor (PR) in the mouse mammary gland that has been used extensively as an experimental model. Studies have led to the concept that progesterone controls proliferation and morphogenesis of the luminal epithelium in a tightly orchestrated manner at distinct stages of development by paracrine signaling pathways, including receptor of activated nuclear factor κ ligand (RANKL) as a major paracrine factor. Progesterone also drives expansion of stem cells by paracrine signals to generate progenitors required for alveologenesis. During mid-to-late pregnancy, progesterone has another role to suppress secretory activation until parturition mediated in part by crosstalk between PR and prolactin/Stat5 signaling to inhibit induction of milk protein gene expression, and by inhibiting tight junction closure. In models of hormone-dependent mouse mammary tumors, the progesterone/PR signaling axis enhances pre-neoplastic progression by a switch from a paracrine to an autocrine mode of proliferation and dysregulation of the RANKL signaling pathway. Limited experiments with normal human breast show that progesterone/PR signaling also stimulates epithelial cell proliferation by a paracrine mechanism; however, the signaling pathways and whether RANKL is a major mediator remains unknown. Work with human breast cancer cell lines, patient tumor samples and clinical studies indicates that progesterone is a risk factor for breast cancer and that alteration in progesterone/PR signaling pathways contributes to early stage human breast cancer progression. However, loss of PR expression in primary tumors is associated with a less differentiated more invasive phenotype and worse prognosis, suggesting that PR may limit later stages of tumor progression. PMID:22193050

  20. Identification of new sialic acids derived from glycoproteins of bovine submandibular gland

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Reuter, G.; Pfeil, R.; Stoll, S.; Schauer, R.; Kamerling, J.P.; Versluis, C.

    1983-01-01

    Improvements in the isolation procedure and the analytical equipment enabled the detection of seven novel sialic acids in bovine submandibular gland glycoprotein: N-acetyl-8-O-acetylneuraminic acid, N-acetyl-8,9-di-O-acetylneuraminic acid, N-acetyl-7,8,9-tri-O-acetylneuraminic acid,

  1. Collision of Ductal Carcinoma In Situ of Anogenital Mammary-like Glands and Vulvar Sarcomatoid Squamous Cell Carcinoma.

    Science.gov (United States)

    Tran, Tien A N; Deavers, Michael T; Carlson, J Andrew; Malpica, Anais

    2015-09-01

    A spectrum of invasive adenocarcinomas presumably arising from the anogenital mammary-like glands of the vulva has been reported. Even rarer are the cases of pure ductal carcinoma in situ that originated from these unique glandular structures. Herein, we report an 81-yr-old woman presented with an invasive well-differentiated squamous cell carcinoma of the vulva. Unexpectedly, the underlying dermis demonstrated a cystically dilated structure that displayed a layer of malignant squamous cells in the periphery, and a second centrally located population of neoplastic cells exhibiting glandular differentiation. In addition, a spindle and pleomorphic malignant cell population consistent with a sarcomatoid carcinoma was identified around the cystic structure. Scattered benign anogenital mammary-like glands were present in the adjacent dermis. The histologic and immunohistochemical findings were consistent with those of vulvar squamous cell carcinoma that has undergone sarcomatoid transformation after spreading in a pagetoid fashion into an underlying focus of ductal carcinoma in situ of anogenital mammary-like gland origin.

  2. Reproductive disturbances, pituitary lactotrope adenomas, and mammary gland tumors in transgenic female mice producing high levels of human chorionic gonadotropin.

    Science.gov (United States)

    Rulli, Susana B; Kuorelahti, Aino; Karaer, Oznur; Pelliniemi, Lauri J; Poutanen, Matti; Huhtaniemi, Ilpo

    2002-10-01

    To assess the consequences of prolonged exposure to elevated levels of LH/human chorionic gonadotropin (hCG) in the female, we developed a transgenic (TG) mouse model (hCGbeta+) that overexpresses the hCGbeta-subunit cDNA. Because of the promoter used, ubiquitin C, the transgene is expressed in multiple tissues, including the pituitary gland, in which coupling with the endogenous common alpha-subunit results in synthesis of high levels of bioactive hCG. The TG females presented with precocious puberty, infertility, enhanced ovarian steroidogenesis, and abnormal uterine structure. Pituitary enlargement was evident from the age of 2 months, which progressed to adenomas by the age of 10-12 months. Immunohistochemical studies and electron microscopy demonstrated lactotrope origin for the adenomas, associated with severe hyperprolactinemia. The mammary glands of TG females showed marked lobuloalveolar development followed by mammary tumors with characteristics of adenocarcinoma at the age of 9-12 months. More than 90% of penetrance and high frequency of metastasis (47%) was observed. Formation of the pituitary and mammary gland tumors was totally abolished by ovariectomy despite persistently elevated hCG levels. Taken together, these findings suggest that the hCG-induced aberrations of ovarian function are clearly responsible for the extragonadal tumors observed in these TG mice.

  3. Description of the prevalence, histologic characteristics, concomitant abnormalities, and outcomes of mammary gland tumors in companion rats (Rattus norvegicus): 100 cases (1990-2015).

    Science.gov (United States)

    Vergneau-Grosset, Claire; Keel, M Kevin; Goldsmith, Dayna; Kass, Philip H; Paul-Murphy, Joanne; Hawkins, Michelle G

    2016-11-15

    OBJECTIVE To describe the prevalence, histologic characteristics, concomitant abnormalities, and outcomes for various types of mammary gland tumors in companion rats (Rattus norvegicus). DESIGN Retrospective case series. ANIMALS 100 client-owned rats. PROCEDURES Medical records of companion rats that had an SC mass and were examined at a veterinary teaching hospital between 1990 and 2015 were reviewed. Information regarding the signalment, age at mass detection, reproductive sterilization status, histologic diagnosis of the SC mass, location of the initial and all subsequent SC masses, treatments administered, and clinical outcomes was extracted from each record and summarized. RESULTS 105 SC masses were initially detected in 100 rats. The most prevalent SC mass identified was mammary gland fibroadenoma (56/105 [53%]), followed by mammary gland carcinoma (13/105 [12%]). Overall, 26 of 105 (25%) masses were malignant. Sexually intact males were more likely to have nonmammary SC tumors than sexually intact females. In rats receiving no adjunctive treatment after excision of a mammary gland fibroadenoma (n = 16), a second fibroadenoma was detected 1 to 8 months after initial excision, at a median of 4.5 months after surgery. A concomitant pituitary gland tumor was identified in most rats with mammary gland fibroadenoma (21/28 [75%]) and other types of mammary gland tumors (10/17 [59%]). Fourteen of 35 (40%) rats with mammary gland fibroadenoma had concomitant reproductive tract abnormalities. CONCLUSION AND CLINICAL RELEVANCE Results suggested that, like other species, companion rats with SC masses should undergo a thorough diagnostic workup that includes histologic examination of the excised mass.

  4. Expression of acute phase proteins and inflammatory cytokines in mouse mammary gland following Staphylococcus aureus challenge and in response to milk accumulation

    DEFF Research Database (Denmark)

    Nazemi, Sasan; Aalbæk, Bent; Kjelgaard-Hansen, Mads

    2014-01-01

    We used a mouse model of pathogenic (Staphylococcus aureus) and non-pathogenic (teat sealing) mammary inflammation to investigate mRNA expression of several inflammatory cytokines and acute phase proteins (APP) in mammary tissue and liver, and the appearance of some of these factors in plasma...... and milk. The expression levels of IL1β and TNFα were markedly up-regulated in Staph. aureus-inoculated mammary tissue at 72 h, whilst IL6 was up-regulated to a lesser extent in a way which was not confined to the inoculated glands. APP expression was up-regulated at 48 and 72 h in both Staph. aureus......-inoculated and teat-sealed mammary glands. These differences between cytokine and APP expression provide additional support for the contention that APPs are produced within the mammary tissue itself during inflammation, rather than in associated immune cells. We propose that measurement of cytokines and APP...

  5. Mammaglobin and S-100 immunoreactivity in salivary gland carcinomas other than mammary analogue secretory carcinoma.

    Science.gov (United States)

    Patel, Kalyani R; Solomon, Isaac H; El-Mofty, Samir K; Lewis, James S; Chernock, Rebecca D

    2013-11-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that has morphologic features similar to secretory carcinoma of the breast and that also harbors the same ETV6 translocation. Diffuse mammaglobin and S-100 immunoreactivity are used to differentiate MASC from its morphologic mimics, especially acinic cell carcinoma and adenocarcinoma, not otherwise specified. However, the combination of mammaglobin and S-100 immunoreactivity has not been well studied in other types of salivary gland carcinomas that may have focal areas reminiscent of MASC. Here we evaluated mammaglobin and S-100 immunoreactivity in 15 cases each of polymorphous low-grade adenocarcinoma, adenoid cystic carcinoma and mucoepidermoid carcinoma, and also in 2 cases of adenocarcinoma, not otherwise specified, and 1 mucinous adenocarcinoma. Cases with significant co-expression of mammaglobin and S-100 (moderate or strong immunoreactivity in >25% of tumor cells) were further analyzed by fluorescence in situ hybridization using the ETV6 (12p13) break-apart probe. Nine cases (60%) of polymorphous low-grade adenocarcinoma and two (13.3%) of adenoid cystic carcinoma met the criteria for significant co-expression of mammaglobin and S-100. All were negative for the ETV6 translocation by fluorescence in situ hybridization. Although mammaglobin and S-100 positivity was seen in the majority of polymorphous low-grade adenocarcinomas and a minority of adenoid cystic carcinomas, none were positive for the ETV6 translocation characteristic of MASC. This indicates a need for caution in the use of immunohistochemistry for diagnosing MASC, especially in the absence of cytogenetic confirmation. © 2013.

  6. Clinicopathologic and molecular characterization of mammary analogue secretory carcinoma of salivary gland origin.

    Science.gov (United States)

    Baghai, F; Yazdani, F; Etebarian, A; Garajei, A; Skalova, A

    2017-09-01

    Mammary analogue secretory carcinoma (MASC) is a newly recognized salivary gland tumor that harbors a characteristic balanced chromosomal translocation t (12; 15) (p13; q25) resulting in an ETV6-NTRK3 fusion gene. Retrospective study of 111 salivary gland carcinomas revealed 37 cases with secretory features and growth patterns resembling secretory carcinoma of breast. These 37 cases were originally diagnosed as acinic cell carcinoma, adenocarcinoma not otherwise specified and cystadenocarcinoma. Positive immunostaining for S-100 protein and mammaglobin, followed by detection of ETV6 gene rearrangement by FISH and/or ETV6-NTRK3 fusion transcript by RT-PCR were used to identify MASCs. In the cohort of 37 salivary carcinomas with secretory features we have identified 10 cases of MASC. All 10 MASCs were positive for mammaglobin, S-100 protein and SOX10, while staining for DOG1 and p63 protein were mostly absent. In 7/10 cases, both FISH and RT-PCR were positive while three remaining cases showed break of ETV6 gene by FISH analysis and the RT-PCR was negative. Clinical follow-up data were obtained in 6 out of 10 patients with MASC. In 3 patients cervical lymph node metastases developed, one patient with high grade transformed MASC died with multiple distant bone metastases, and local recurrence was observed in three patients. Our clinicopathological data are in keeping with previous studies; in most cases, MASC is a low-grade malignancy with overall favorable prognosis. In rare cases, however, MASC with high-grade transformation may behave aggressively, and these patients could benefit from targeted biological treatment using tyrosine kinase inhibitors. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. Production and processing of milk from transgenic goats expressing human lysozyme in the mammary gland.

    Science.gov (United States)

    Maga, E A; Shoemaker, C F; Rowe, J D; Bondurant, R H; Anderson, G B; Murray, J D

    2006-02-01

    The potential for applying biotechnology to benefit animal agriculture and food production has long been speculated. The addition of human milk components with intrinsic antimicrobial activity and positive charge to livestock milk by genetic engineering has the potential to benefit animal health, as well as food safety and production. We generated one line of transgenic goats as a model for the dairy cow designed to express human lysozyme in the mammary gland. Here we report the characterization of the milk from 5 transgenic females of this line expressing human lysozyme in their milk at 270 microg/mL or 68% of the level found in human milk. Milk from transgenic animals had a lower somatic cell count, but the overall component composition of the milk and milk production were not different from controls. Milk from transgenic animals had a shorter rennet clotting time and increased curd strength. Milk of such nature may be of benefit to the producer by influencing udder health and milk processing.

  8. The Infrared Radiation Temperature Characteristic of Acupoints of Mammary Gland Hyperplasia Patients

    Directory of Open Access Journals (Sweden)

    Juanjuan Zheng

    2013-01-01

    Full Text Available Objective. To ascertain pathological information on hyperplasia of mammary glands (HMG of patients via the infrared radiation temperature of acupoints. Method. Patients with HMG and healthy controls were tested using an infrared thermal imager. Results. In controls, no significant difference in temperature was observed between points with the same name (P>0.05. The temperature of all tested points was found to be higher in the group with HMG than in that of the healthy controls, except for the left and right Zusanli (ST36. The temperature of the right Rugen (ST18, Guanyuan (CV4, Qihai (CV6, and Hegu (LI4 reached a statistically significant heightened level (P=0.046~P<0.001. The temperature of the Zusanli (ST36 and Hegu (LI4 present on the right side was significantly higher than that of the left (P=0.001 and P=0.004, resp., while the temperature of the left Youmen (KI21 was significantly higher than that of the right (P=0.008. Conclusion. The temperature of the bilateral acupoints in healthy controls was symmetrical, and the raised temperatures observed of the Rugen (ST18, Guanyuan (CV4, Qihai (CV6, and Hegu (LI4 acupoints of HMG patients and the imbalance of the temperature of the bilateral acupoints Zusanli (ST36, Youmen (KI21, and Hegu (LI4 carried special pathological information about HMG disease.

  9. CSF-1R signaling in health and disease: a focus on the mammary gland.

    Science.gov (United States)

    Sullivan, Amy Renee; Pixley, Fiona Jane

    2014-07-01

    Colony-stimulating factor-1 (CSF-1), also known as macrophage-colony stimulating factor (M-CSF), is the primary growth factor regulating survival, proliferation and differentiation of macrophages. It is also a potent chemokine for macrophages and monocytes. Signaling via the CSF-1 receptor (CSF-1R) is necessary for the production of almost all tissue resident macrophage populations and these macrophages participate, via trophic mechanisms, in the normal development and homeostasis of tissues and organs in which they reside, including the mammary gland. The drawback of this close interaction between macrophages and parenchymal cells is that dysregulation of macrophage trophic functions assists in the development and progression of many cancers, including breast cancer. Furthermore, tumour cells secrete CSF-1 to attract more macrophages to the tumour microenvironment where CSF-1R signaling frequently drives the behaviour of these tumour-associated macrophages (TAMs) to promote tumour progression and metastasis. Evidence is mounting that treated tumours secrete more CSF-1 and the increased recruitment of TAMs limits treatment efficacy. Thus, therapeutic targeting of the CSF-1R to inhibit TAM function is likely to enhance tumour response and improve patient outcomes in the treatment of cancer, including breast cancer.

  10. microRNAs and the mammary gland: a new understanding of gene expression

    Directory of Open Access Journals (Sweden)

    Isabel Gigli

    2013-01-01

    Full Text Available MicroRNAs (miRNAs have been identified in cells as well as in exosomes in biological fluids such as milk. In mammary gland, most of the miRNAs studied have functions related to immunity and show alterations in their pattern of expression during lactation. In mastitis, the inflammatory response caused by Streptococcus uberis alters the expression of miRNAs that may regulate the innate immune system. These small RNAs are stable at room temperature and are resistant to repeated freeze/thaw cycles, acidic conditions and degradation by RNAse, making them resistant to industrial procedures. These properties mean that miRNAs could have multiple applications in veterinary medicine and biotechnology. Indeed, lactoglobulin-free milk has been produced in transgenic cows expressing specific miRNAs. Although plant and animal miRNAs have undergone independent evolutionary adaptation recent studies have demonstrated a cross-kingdom passage in which rice miRNA was isolated from human serum. This finding raises questions about the possible effect that miRNAs present in foods consumed by humans could have on human gene regulation. Further studies are needed before applying miRNA biotechnology to the milk industry. New discoveries and a greater knowledge of gene expression will lead to a better understanding of the role of miRNAs in physiology, nutrition and evolution.

  11. Automatic segmentation of histological structures in normal and neoplastic mammary gland tissue sections

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Gonzalez, Rodrigo; Deschamps, Thomas; Idica, Adam K.; Malladi, Ravi; Ortiz de Solorzano, Carlos

    2003-01-18

    In this paper we present a scheme for real time segmentation of histological structures in microscopic images of normal and neoplastic mammary gland sections. Paraffin embedded or frozen tissue blocks are sliced, and sections are stained with hematoxylin and eosin (H&E). The sections are then imaged using conventional bright field microscopy. The background of the images is corrected by arithmetic manipulation using a ''phantom.'' Then we use the fast marching method with a speed function that depends on the brightness gradient of the image to obtain a preliminary approximation to the boundaries of the structures of interest within a region of interest (ROI) of the entire section manually selected by the user. We use the result of the fast marching method as the initial condition for the level set motion equation. We run this last method for a few steps and obtain the final result of the segmentation. These results can be connected from section to section to build a three-dimensional reconstruction of the entire tissue block that we are studying.

  12. Ceruloplasmin gene expression profile changes in the rat mammary gland during pregnancy, lactation and involution.

    Science.gov (United States)

    Platonova, Natalia A; Orlov, Iurii A; Klotchenko, Sergey A; Babich, Victor S; Ilyechova, Ekaterina Y; Babich, Polina S; Garmai, Yuri P; Vasin, Andrey V; Tsymbalenko, Nadezhda V; Puchkova, Liudmila V

    2017-09-01

    Copper metabolism disturbances in mammary gland (MG) cells have severe consequences in newborns. The mechanism that controls the balance of copper in the MG has not been thoroughly characterized. Four primary copper homeostasis genes in mammals: (1) ceruloplasmin (Cp) encoding multifunction multicopper blue (ferr)oxidase; (2) CTR1 encoding high affinity copper importer 1; and (3 and 4) two similar genes encoding Cu(I)/Cu(II)-ATPases P1 type (ATP7A and ATP7B) responsible for copper efflux from the cells and metallation of cuproenzymes formed in the Golgi complex are expressed in MG. This study aimed to characterize expression of these genes during pregnancy, lactation and forced involution in the rat MG. We found that Cp anchored to the plasma membrane and ATP7A were expressed during pregnancy and lactation. Soluble Cp and ATP7B were highly expressed in lactating MG decreasing to its ending. CTR1 activity increased during MG growth and reached its maximum at postpartum and then it decreased until the end of lactation. During early forced MG involution, Cp gene expression persisted; while a form of Cp that lacked exon 18 appeared. We suggest that Cp gene expressional changes at the transcriptional and posttranscriptional level reflect various physiological functions of Cp proteins during MG remodeling. Copyright © 2017 Elsevier GmbH. All rights reserved.

  13. Keeping Abreast with long non-coding RNAs in mammary gland development and breast cancer

    Directory of Open Access Journals (Sweden)

    Herah eHansji

    2014-10-01

    Full Text Available The majority of the human genome is transcribed, even though only 2% of transcripts encode proteins. Non-coding transcripts were originally dismissed as evolutionary junk or transcriptional noise, but with the development of whole genome technologies, these ncRNAs are emerging as molecules with vital roles in regulating gene expression. While shorter ncRNAs have been extensively studied, the functional roles of long non-coding RNAs are still being elucidated. Studies over the last decade show that lncRNAs are emerging as new players in a number of diseases including cancer. Potential roles in both oncogenic and tumour suppressive pathways in cancer have been elucidated, but the biological functions of the majority of lncRNAs remain to be identified. Accumulated data are identifying the molecular mechanisms by which lncRNA mediates both structural and functional roles. LncRNA can regulate gene expression at both transcriptional and post-transcriptional levels, including splicing and regulating mRNA processing, transport and translation. Much current research is aimed at elucidating the function of lncRNAs in breast cancer and mammary gland development, and at identifying the cellular processes influenced by lncRNAs. In this paper we review current knowledge of lncRNAs contributing to these processes and present lncRNA as a new paradigm in breast cancer development.

  14. LPA receptor activity is basal specific and coincident with early pregnancy and involution during mammary gland postnatal development

    Science.gov (United States)

    Acosta, Deanna; Bagchi, Susmita; Broin, Pilib Ó; Hollern, Daniel; Racedo, Silvia E.; Morrow, Bernice; Sellers, Rani S.; Greally, John M.; Golden, Aaron; Andrechek, Eran; Wood, Teresa; Montagna, Cristina

    2016-01-01

    During pregnancy, luminal and basal epithelial cells of the adult mammary gland proliferate and differentiate resulting in remodeling of the adult gland. While pathways that control this process have been characterized in the gland as a whole, the contribution of specific cell subtypes, in particular the basal compartment, remains largely unknown. Basal cells provide structural and contractile support, however they also orchestrate the communication between the stroma and the luminal compartment at all developmental stages. Using RNA-seq, we show that basal cells are extraordinarily transcriptionally dynamic throughout pregnancy when compared to luminal cells. We identified gene expression changes that define specific basal functions acquired during development that led to the identification of novel markers. Enrichment analysis of gene sets from 24 mouse models for breast cancer pinpoint to a potential new function for insulin-like growth factor 1 (Igf1r) in the basal epithelium during lactogenesis. We establish that β-catenin signaling is activated in basal cells during early pregnancy, and demonstrate that this activity is mediated by lysophosphatidic acid receptor 3 (Lpar3). These findings identify novel pathways active during functional maturation of the adult mammary gland. PMID:27808166

  15. Viral infections and bovine mastitis: a review.

    Science.gov (United States)

    Wellenberg, G J; van der Poel, W H M; Van Oirschot, J T

    2002-08-02

    This review deals with the role of viruses in the aetiology of bovine mastitis. Bovine herpesvirus 1, bovine herpesvirus 4, foot-and-mouth disease virus, and parainfluenza 3 virus have been isolated from milk from cows with clinical mastitis. Intramammary inoculations of bovine herpesvirus 1 or parainfluenza 3 virus-induced clinical mastitis, while an intramammary inoculation of foot-and-mouth disease virus resulted in necrosis of the mammary gland. Subclinical mastitis has been induced after a simultaneous intramammary and intranasal inoculation of lactating cows with bovine herpesvirus 4. Bovine leukaemia virus has been detected in mammary tissue of cows with subclinical mastitis, but whether this virus was able to induce bovine mastitis has not been reported. Bovine herpesvirus 2, vaccinia, cowpox, pseudocowpox, vesicular stomatitis, foot-and-mouth disease viruses, and bovine papillomaviruses can play an indirect role in the aetiology of bovine mastitis. These viruses can induce teat lesions, for instance in the ductus papillaris, which result in a reduction of the natural defence mechanisms of the udder and indirectly in bovine mastitis due to bacterial pathogens. Bovine herpesvirus 1, bovine viral diarrhoea virus, bovine immunodeficiency virus, and bovine leukaemia virus infections may play an indirect role in bovine mastitis, due to their immunosuppressive properties. But, more research is warranted to underline their indirect role in bovine mastitis. We conclude that viral infections can play a direct or indirect role in the aetiology of bovine mastitis; therefore, their importance in the aetiology of bovine mastitis and their economical impact needs further attention.

  16. Effects of short- and long-chain fatty acids on the expression of stearoyl-CoA desaturase and other lipogenic genes in bovine mammary epithelial cells.

    Science.gov (United States)

    Jacobs, A A A; Dijkstra, J; Liesman, J S; Vandehaar, M J; Lock, A L; van Vuuren, A M; Hendriks, W H; van Baal, J

    2013-09-01

    Stearoyl-CoA desaturase (SCD) in the bovine mammary gland introduces a cis-double bond at the Δ9 position in a wide range of fatty acids (FA). Several long-chain polyunsaturated fatty acids (PUFA) inhibit expression of SCD, but information on the effect of short-chain fatty acids on mammary SCD expression is scarce. We used a bovine mammary cell line (MAC-T) to assess the effect of acetic acid (Ac) and β-hydroxybutyric acid (BHBA) in comparison with the effect of various long-chain fatty acids on the mRNA expression of the lipogenic enzymes SCD, acetyl-CoA carboxylase (ACACA), fatty acid synthase (FASN) and their associated gene regulatory proteins sterol regulatory element binding transcription factor 1 (SREBF1), insulin-induced gene 1 protein (INSIG1) and peroxisome proliferator-activated receptor alpha (PPARA)and peroxisome proliferator-activated receptor delta (PPARD) by quantitative real-time PCR. MAC-T cells were treated for 12 h without FA additions (CON) or with either 5 mM Ac, 5 mM BHBA, a combination of 5 mM Ac + 5 mM BHBA, 100 μM C16:0, 100 μM C18:0, 100 μM C18:1 cis-9, 100 μM C18:1 trans-11, 100 μM C18:2 cis-9,12 or 100 μM C18:3 cis-9,12,15. Compared with control, mRNA expression of SCD1 was increased by Ac (+61%) and reduced by C18:1 cis-9 (-61%), C18:2 cis-9,12 (-84%) and C18:3 cis-9,12,15 (-88%). In contrast to native bovine mammary gland tissue, MAC-T cells did not express SCD5. Expression of ACACA was increased by Ac (+44%) and reduced by C18:2 cis-9,12 (-48%) and C18:3 cis-9,12,15 (-49%). Compared with control, FASN expression was not significantly affected by the treatments. The mRNA level of SREBF1 was not affected by Ac or BHBA, but was reduced by C18:1 cis-9 (-44%), C18:1 trans-11 (-42%), C18:2 cis-9,12 (-62%) and C18:3 cis-9,12,15 (-68%) compared with control. Expression of INSIG1 was downregulated by C18:0 (-37%), C18:1 cis-9 (-63%), C18:1 trans-11 (-53%), C18:2 cis-9,12 (-81%) and C18:3 cis-9,12,15 (-91%). Both PPARA and PPARD

  17. Mammary gland-specific ablation of focal adhesion kinase reduces the incidence of p53-mediated mammary tumour formation.

    NARCIS (Netherlands)

    Miltenburg, van M.H.; Nimwegen, van M.J.; Tijdens, R.B.; Lalai, R.A.; Kuiper, R.; Klarenbeek, S.; Schouten, P.C.; Vries, de A.; Jonkers, J.M.M.; Water, van de B.

    2014-01-01

    BACKGROUND Elevated expression of focal adhesion kinase (FAK) occurs in numerous human cancers including colon-, cervix- and breast cancer. Although several studies have implicated FAK in mammary tumour formation induced by ectopic oncogene expression, evidence supporting a role for FAK in

  18. Proliferative effects of combination estrogen and progesterone replacement therapy on the normal postmenopausal mammary gland in a murine model.

    Science.gov (United States)

    Raafat, A M; Hofseth, L J; Haslam, S Z

    2001-02-01

    The aim of the study was to analyze the proliferative response of the normal mammary gland to combination hormone replacement therapy with estrogen and progesterone in a murine model of early versus late postmenopausal states. Ovariectomized mice were injected daily for up to 56 days with estrogen plus progesterone, starting at either 1 or 5 weeks after ovariectomy to simulate early and late menopausal periods, respectively. At various times after treatment, proliferation was analyzed by deoxyribonucleic acid histoautoradiography and whole-mount preparations. The induction of progesterone receptor by estrogen was also analyzed. To distinguish between estrogen- and progesterone-specific responses, we tested the effects of the antiprogesterone mifepristone (RU 486) and the antiestrogen ICI 182,780. The acute response to estrogen-progesterone therapy in the early postmenopausal period resulted in duct-end enlargement, ductal side branching, alveolar bud formation, and a 100-fold increase in epithelial cell proliferation. This was caused by the dominant effect of progesterone acting through the progesterone receptor. In the late postmenopausal period the acute response produced only duct-end enlargement; the 100-fold increase in epithelial cell proliferation resulted from the dominant effect of estrogen. After long-term treatment, both early and late postmenopausal glands exhibited similar morphologic features and a 9-fold higher steady-state proliferation rate than was found in control-treated groups. Starting combined estrogen and progesterone hormone replacement therapy in either early or late postmenopause produced a persistent, steady-state 9-fold increase in epithelial cell proliferation, which could be a contributing factor to increased breast cancer risk. The acute response in the late postmenopausal period mimics the hormonal response of the pubertal mammary gland, which in rodents is the stage most susceptible to carcinogen-induced mammary tumorigenesis

  19. High resolution 3D MRI of mouse mammary glands with intra-ductal injection of contrast media.

    Science.gov (United States)

    Markiewicz, Erica; Fan, Xiaobing; Mustafi, Devkumar; Zamora, Marta; Roman, Brian B; Jansen, Sanaz A; Macleod, Kay; Conzen, Suzanne D; Karczmar, Gregory S

    2015-01-01

    The purpose of this study was to use high resolution three-dimensional (3D) magnetic resonance imaging (MRI) to study mouse mammary gland ductal architecture based on intra-ductal injection of contrast agents. Female FVB/N mice age 12-20 weeks (n=12), were used in this study. A 34G, 45° tip Hamilton needle with a 25μL Hamilton syringe was inserted into the tip of the nipple. Approximately 20-25μL of a Gadodiamide/Trypan blue/saline solution was injected slowly over one minute into the nipple and duct. To prevent washout of contrast media from ducts due to perfusion, and maximize the conspicuity of ducts on MRI, mice were sacrificed one minute after injection. High resolution 3D T1-weighted images were acquired on a 9.4T Bruker scanner after sacrifice to eliminate motion artifacts and reduce contrast media leakage from ducts. Trypan blue staining was well distributed throughout the ductal tree. MRI showed the mammary gland ductal structure clearly. In spoiled gradient echo T1-weighted images, the signal-to-noise ratio of regions identified as enhancing mammary ducts following contrast injection was significantly higher than that of muscle (pcontrast media (pcontrast agents to measure metabolism or target receptors in normal ducts and ducts with in situ cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Genetic suppression reveals DNA repair-independent antagonism between BRCA1 and COBRA1 in mammary gland development

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    Nair, Sreejith J.; Zhang, Xiaowen; Chiang, Huai-Chin; Jahid, Md Jamiul; Wang, Yao; Garza, Paula; April, Craig; Salathia, Neeraj; Banerjee, Tapahsama; Alenazi, Fahad S.; Ruan, Jianhua; Fan, Jian-Bing; Parvin, Jeffrey D.; Jin, Victor X.; Hu, Yanfen; Li, Rong

    2016-01-01

    The breast cancer susceptibility gene BRCA1 is well known for its function in double-strand break (DSB) DNA repair. While BRCA1 is also implicated in transcriptional regulation, the physiological significance remains unclear. COBRA1 (also known as NELF-B) is a BRCA1-binding protein that regulates RNA polymerase II (RNAPII) pausing and transcription elongation. Here we interrogate functional interaction between BRCA1 and COBRA1 during mouse mammary gland development. Tissue-specific deletion of Cobra1 reduces mammary epithelial compartments and blocks ductal morphogenesis, alveologenesis and lactogenesis, demonstrating a pivotal role of COBRA1 in adult tissue development. Remarkably, these developmental deficiencies due to Cobra1 knockout are largely rescued by additional loss of full-length Brca1. Furthermore, Brca1/Cobra1 double knockout restores developmental transcription at puberty, alters luminal epithelial homoeostasis, yet remains deficient in homologous recombination-based DSB repair. Thus our genetic suppression analysis uncovers a previously unappreciated, DNA repair-independent function of BRCA1 in antagonizing COBRA1-dependent transcription programme during mammary gland development. PMID:26941120

  1. Metastatic mammary carcinoma in a cow

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    Manoela Marchezan Piva

    Full Text Available ABSTRACT: Mammary gland neoplasms in cattle are rarely observed in the field veterinary diagnostics routine. Therefore, the objective of this study is to report a metastatic mammary carcinoma in a fourteen-year-old Holstein cow in the state of Santa Catarina, Brazil. The animal was diagnosed by the field veterinarian with clinical mastitis that was unresponsive to treatment, and was euthanized due to the poor prognosis. At the necropsy, multiple yellow, firm, and sometimes friable nodules, ranging from 0.1 to 20cm were observed in all mammary glands, lymph nodes, kidneys, spleen, liver, pancreas, mediastinal lymph nodes, heart, and lungs. The final diagnosis of mammary carcinoma was established through the association of clinical, necropsy, histopathological, and immunohistochemical findings. Differential diagnoses included diseases such as bovine tuberculosis and chronic fungal or bacterial mastitis.

  2. Anti-tumour effect of metformin in canine mammary gland tumour cells.

    Science.gov (United States)

    Saeki, K; Watanabe, M; Tsuboi, M; Sugano, S; Yoshitake, R; Tanaka, Y; Ong, S M; Saito, T; Matsumoto, K; Fujita, N; Nishimura, R; Nakagawa, T

    2015-08-01

    Metformin is an oral hypoglycaemic drug used in type 2 diabetes. Its pharmacological activity reportedly involves mitochondrial respiratory complex I, and mitochondrial respiratory complex inhibitors have a strong inhibitory effect on the growth of metastatic canine mammary gland tumour (CMGT) cell lines. It is hypothesised that metformin has selective anti-tumour effects on metastatic CMGT cells. The aim of this study was to investigate the in vitro effect of metformin on cell growth, production of ATP and reactive oxygen species (ROS), and the AMP-activated protein kinase (AMPK) mammalian target of rapamycin (mTOR) pathway in two CMGT clonal cell lines with different metastatic potential. In addition, transcriptome analysis was used to determine cellular processes disrupted by metformin and in vivo anti-tumour effects were examined in a mouse xenograft model. Metformin inhibited CMGT cell growth in vitro, with the metastatic clone (CHMp-5b) displaying greater sensitivity. ATP depletion and ROS elevation were observed to a similar extent in the metastatic and non-metastatic (CHMp-13a) cell lines after metformin exposure. However, subsequent AMPK activation and mTOR pathway inhibition were prominent only in metformin-insensitive non-metastatic cells. Microarray analysis revealed inhibition of cell cycle progression by metformin treatment in CHMp-5b cells, which was further confirmed by Western blotting and cell cycle analysis. Additionally, metformin significantly suppressed tumour growth in xenografted metastatic CMGT cells. In conclusion, metformin exhibited an anti-tumour effect in metastatic CMGT cells through AMPK-independent cell cycle arrest. Its mechanism of action differed in the non-metastatic clone, where AMPK activation and mTOR inhibition were observed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Estrogen Effects on the Mammary Gland in Early and Late Life and Breast Cancer Risk

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    Genevieve Victoria Dall

    2017-05-01

    Full Text Available A woman has an increased risk of breast cancer if her lifelong estrogen exposure is increased due to an early menarche, a late menopause, and/or an absence of childbearing. For decades, it was presumed that the number of years of exposure drove the increased risk, however, recent epidemiological data have shown that early life exposure (young menarche has a more significant effect on cancer risk than late menopause. Thus, rather than the overall exposure it seems that the timing of hormone exposure plays a major role in defining breast cancer risk. In support of this, it is also known that aberrant hormonal exposure prior to puberty can also increase breast cancer risk, yet the elevated estrogen levels during pregnancy decrease breast cancer risk. This suggests that the effects of estrogen on the mammary gland/breast are age-dependent. In this review article, we will discuss the existing epidemiological data linking hormone exposure and estrogen receptor-positive breast cancer risk including menarche, menopause, parity, and aberrant environmental hormone exposure. We will discuss the predominantly rodent generated experimental data that confirm the association with hormone exposure and breast cancer risk, confirming its use as a model system. We will review the work that has been done attempting to define the direct effects of estrogen on the breast, which are beginning to reveal the mechanism of increased cancer risk. We will then conclude with our views on the most pertinent questions to be addressed experimentally in order to explore the relationship between age, estrogen exposure, and breast cancer risk.

  4. Absence of significant adverse events following thalidomide administration in bitches diagnosed with mammary gland carcinomas.

    Science.gov (United States)

    de Campos, C B; Lavalle, G E; Fialho Ligório, S; Camargo Nunes, F; Carneiro, R A; Amorim, R L; Cassali, G D

    2016-11-19

    The aim of the study was to evaluate the incidence of adverse events (AEs) in female dogs diagnosed with advanced clinical stage mammary gland neoplasms following treatment with thalidomide. A prospective analysis of 29 female dogs treated with a high dose (HD) of 20 mg/kg/day of thalidomide for three months followed by a low dose (LD) of 10 mg/kg/day of thalidomide for three months was performed. All patients underwent physical examination, complete blood count, serum biochemistry profile, thoracic radiographs, and abdominal ultrasound analysis before the treatment and after the HD and LD. Clinical AEs were absent in 16/29 (55.17 per cent) patients following HD. An initial 3-5 day period of somnolence was described in 4/29 (13.79 per cent), prolonged somnolence in 5/29 (17.24 per cent), a short period of somnolence lasting only a few hours in 3/29 (10.34 per cent), and difficulty to rouse was described in 5/29 (17.24 per cent) cases. Two patients (6.89 per cent) presented with prolonged somnolence that interfered with activities of daily living, resulting in anticipation of the dose reduction to the proposed LD after 15 days of the HD treatment. Following dose reduction, AE improvement was observed in all patients. Albeit remaining within the reference ranges, erythrocytes, haematocrit, total leucocyte count, neutrophils, lymphocytes, monocytes and γ-glutamyltranspeptidase showed significant alteration associated to thalidomide treatment. British Veterinary Association.

  5. Mammary analogue secretory carcinoma of salivary glands: a clinicopathologic study of 11 cases.

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    Din, Nasir Ud; Fatima, Saira; Kayani, Naila

    2016-06-01

    Mammary analogue secretory carcinoma (MASC) is a recently described tumor sharing the histologic, immunohistochemical, and molecular profile of secretory carcinoma of breast. We aimed to evaluate the morphologic and histochemical features needed/required for the diagnosis of MASC without adjunct of molecular analysis. Six retrospective cases suspicious for MASC and 5 prospective cases reported as MASC were included in the study. Molecular analysis of ETV6 by fluorescence in situ hybridization was performed at the University of Pittsburg, USA. The ages of the patients ranged from 9 to 60 years (mean, 27.5 years). Histologically, all tumors showed mixed growth patterns including microcystic, macrocystic, papillary, tubular, and solid, papillary the being most common pattern. The tumor cells showed round to oval vesicular nuclei with small nucleoli, and eosinophilic to vacuolated cytoplasm. All cases demonstrated luminal and cytoplasmic mucin on periodic acid-Schiff with and without diastase digestion and alcian blue stain. ETV6 fusion gene rearrangement by fluorescence in situ hybridization was detected in 10 of 11 tumors. Recurrences occurred in 3 patients, and 1 patient died of disease 5 years after surgery. In conclusion, MASC is a relatively rare salivary gland malignancy exhibiting distinct histologic and histochemical features which can help to differentiate it from other mimics. Histologically, papillary-cystic and microcystic patterns are the main clues to diagnosis. The follicular pattern of acinic cell carcinoma might represent MASC, as 4 cases in our series had this pattern. Two patients in our series were 9 and 9½ years old respectively, which are the youngest ages ever recorded for MASC. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Prototheca zopfii Induced Ultrastructural Features Associated with Apoptosis in Bovine Mammary Epithelial Cells.

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    Shahid, Muhammad; Wang, Jianfang; Gu, Xiaolong; Chen, Wei; Ali, Tariq; Gao, Jian; Han, Dandan; Yang, Rui; Fanning, Séamus; Han, Bo

    2017-01-01

    Prototheca zopfii infections are becoming global concerns in humans and animals. Bovine protothecal mastitis is characterized by deteriorating milk quality and quantity, thus imparting huge economic losses to dairy industry. Previous published studies mostly focused on the prevalence and characterization of P. zopfii from mastitis. However, the ultrastructural pathomorphological changes associated with apoptosis in bovine mammary epithelial cells (bMECs) are not studied yet. Therefore, in this study we aimed to evaluate the in vitro comparative apoptotic potential of P. zopfii genotype-I and -II on bMECs using flow cytometry, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The results showed fast growth rate and higher adhesion capability of genotype-II in bMECs as compared with genotype-I. The viability of bMECs infected with P. zopfii genotype-II was significantly decreased after 12 h (p effects on cell viability. Moreover, after infection of bMECs with genotype-II, the apoptosis increased significantly at 12 h (p effects on cell apoptosis. The host specificity of P. zopfii was also tested in mouse osteoblast cells, and the results suggest that genotype-I and -II could not cause any significant apoptosis in these cell lines. SEM interpreted the pathomorphological alterations in bMECs after infection. Adhesion of P. zopfii with cells and further disruption of cytomembrane validated the apoptosis caused by genotype-II under SEM. While genotype-1 couldn't cause any significant apoptosis in bMECs. Furthermore, genotype-II induced apoptotic manifested specific ultrastructure features, like cytoplasmic cavitation, swollen mitochondria, pyknosis, cytomembrane disruption, and appearance of apoptotic bodies under TEM. The findings of the current study revealed that genotype-II has the capability to invade and survive within the bMECs, thus imparting significant damages to the mammary cells which result in apoptosis. This study represents

  7. Prototheca zopfii Induced Ultrastructural Features Associated with Apoptosis in Bovine Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Muhammad Shahid

    2017-07-01

    Full Text Available Prototheca zopfii infections are becoming global concerns in humans and animals. Bovine protothecal mastitis is characterized by deteriorating milk quality and quantity, thus imparting huge economic losses to dairy industry. Previous published studies mostly focused on the prevalence and characterization of P. zopfii from mastitis. However, the ultrastructural pathomorphological changes associated with apoptosis in bovine mammary epithelial cells (bMECs are not studied yet. Therefore, in this study we aimed to evaluate the in vitro comparative apoptotic potential of P. zopfii genotype-I and -II on bMECs using flow cytometry, scanning electron microscopy (SEM, and transmission electron microscopy (TEM. The results showed fast growth rate and higher adhesion capability of genotype-II in bMECs as compared with genotype-I. The viability of bMECs infected with P. zopfii genotype-II was significantly decreased after 12 h (p < 0.05 and 24 h (p < 0.01 in comparison with control cells. Contrary, genotype-I couldn't show any significant effects on cell viability. Moreover, after infection of bMECs with genotype-II, the apoptosis increased significantly at 12 h (p < 0.05 and 24 h (p < 0.01 as compared with control group. Genotype-I couldn't display any significant effects on cell apoptosis. The host specificity of P. zopfii was also tested in mouse osteoblast cells, and the results suggest that genotype-I and -II could not cause any significant apoptosis in these cell lines. SEM interpreted the pathomorphological alterations in bMECs after infection. Adhesion of P. zopfii with cells and further disruption of cytomembrane validated the apoptosis caused by genotype-II under SEM. While genotype-1 couldn't cause any significant apoptosis in bMECs. Furthermore, genotype-II induced apoptotic manifested specific ultrastructure features, like cytoplasmic cavitation, swollen mitochondria, pyknosis, cytomembrane disruption, and appearance of apoptotic bodies under

  8. Supplements of vitamins B9 and B12 affect hepatic and mammary gland gene expression profiles in lactating dairy cows.

    Science.gov (United States)

    Ouattara, Bazoumana; Bissonnette, Nathalie; Duplessis, Melissa; Girard, Christiane L

    2016-08-15

    A combined supplement of vitamins B9 and B12 was reported to increase milk and milk component yields of dairy cows without effect on feed intake. The present study was undertaken to verify whether this supplementation positively modifies the pathways involved in milk and milk component synthesis. Thus, by studying the transcriptome activity in these tissues, the effect of supplements of both vitamins on the metabolism of both liver and mammary gland, was investigated. For this study, 24 multiparous Holstein dairy cows were assigned to 6 blocks of 4 animals each according to previous 305-day milk production. Within each block, cows were randomly assigned to weekly intramuscular injections of 5 mL of either saline 0.9 % NaCl, 320 mg of vitamin B9, 10 mg of vitamin B12 or a combination of both vitamins (B9 + B12). The experimental period began 3 weeks before the expected calving date and lasted 9 weeks of lactation. Liver and mammary biopsies were performed on lactating dairy cows 64 ± 3 days after calving. Samples from both tissues were analyzed by microarray and qPCR to identify genes differentially expressed in hepatic and mammary tissues. Microarray analysis identified 47 genes in hepatic tissue and 16 genes in the mammary gland whose expression was modified by the vitamin supplements. Gene ontology (GO) categorizes genes in non-overlapping domains of molecular biology. Panther is one of the online GO resources used for gene function classification. It classifies the 63 genes according to Molecular Function, Biological Process and Protein Class. Most of the biological processes modulated by the vitamin supplements were associated to developmental process, protein metabolic process, transport and response to inflammation. In the liver, most of the genes modulated by the vitamin treatments involved protein metabolic process while developmental process appeared to be more affected by the treatments in mammary gland. Out of 25 genes analysed by qPCR, 7

  9. XBP1 Regulates the Biosynthetic Capacity of the Mammary Gland During Lactation by Controlling Epithelial Expansion and Endoplasmic Reticulum Formation.

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    Davis, Kristen R; Giesy, Sarah L; Long, Qiaoming; Krumm, Christopher S; Harvatine, Kevin J; Boisclair, Yves R

    2016-01-01

    Cells composing the mammary secretory compartment have evolved a high capacity to secrete not only proteins but also triglycerides and carbohydrates. This feature is illustrated by the mouse, which can secrete nearly twice its own weight in milk proteins, triglycerides and lactose over a short 20-day lactation. The coordination of synthesis and export of products in other secretory cells is orchestrated in part by the transcription factor X-box binding protein 1 (XBP1). To assess the role of XBP1 in mammary epithelial cells (MEC), we studied floxed XBP1 female mice lacking (wild type; WT) or expressing the Cre recombinase under the control of the ovine β-lactoglobulin promoter (ΔXBP1(MEC)). Pregnant ΔXBP1(MEC) females had morphologically normal mammary development and gave birth to the same number of pups as WT mice. Their litters, however, suffered a weight gain deficit by lactation day 3 (L3)3 that grew to 80% by L14. ΔXBP1(MEC) dams had only modest changes in milk composition (-21% protein, +24% triglyceride) and in the expression of associated genes in isolated MEC. By L5, WT glands were fully occupied by dilated alveoli, whereas ΔXBP1(MEC) glands contained fewer, mostly unfilled alveoli and retained a prominent adipocyte population. The smaller epithelial compartment in ΔXBP1(MEC) glands was explained by lower MEC proliferation and increased apoptosis. Finally, endoplasmic reticulum ribbons were less abundant in ΔXBP1(MEC) at pregnancy day 18 and failed to increase in abundance by L5. Collectively, these results show that XBP1 is required for MEC population expansion during lactation and its ability to develop an elaborate endoplasmic reticulum compartment.

  10. Regucalcin expression in bovine tissues and its regulation by sex steroid hormones in accessory sex glands.

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    Laura Starvaggi Cucuzza

    Full Text Available Regucalcin (RGN is a mammalian Ca2+-binding protein that plays an important role in intracellular Ca2+ homeostasis. Recently, RGN has been identified as a target gene for sex steroid hormones in the prostate glands and testis of rats and humans, but no studies have focused on RGN expression in bovine tissues. Thus, in the present study, we examined RGN mRNA and protein expression in the different tissues and organs of veal calves and beef cattle. Moreover, we investigated whether RGN expression is controlled through sex steroid hormones in bovine target tissues, namely the bulbo-urethral and prostate glands and the testis. Sex steroid hormones are still illegally used in bovine husbandry to increase muscle mass. The screening of the regulation and function of anabolic sex steroids via modified gene expression levels in various tissues represents a new approach for the detection of illicit drug treatments. Herein, we used quantitative PCR, western blot and immunohistochemistry analyses to demonstrate RGN mRNA and protein expression in bovine tissues. In addition, estrogen administration down-regulated RGN gene expression in the accessory sex glands of veal calves and beef cattle, while androgen treatment reduced RGN gene expression only in the testis. The confirmation of the regulation of RGN gene expression through sex steroid hormones might facilitate the potential detection of hormone abuse in bovine husbandry. Particularly, the specific response in the testis suggests that this tissue is ideal for the detection of illicit androgen administration in veal calves and beef cattle.

  11. Over-expression of human lipoprotein lipase in mouse mammary glands leads to reduction of milk triglyceride and delayed growth of suckling pups.

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    Yuanyuan Wang

    Full Text Available BACKGROUND: The mammary gland is a conserved site of lipoprotein lipase expression across species and lipoprotein lipase attachment to the luminal surface of mammary gland vascular endothelial cells has been implicated in the direction of circulating triglycerides into milk synthesis during lactation. PRINCIPAL FINDINGS: Here we report generation of transgenic mice harboring a human lipoprotein lipase gene driven by a mammary gland-specific promoter. Lipoprotein lipase levels in transgenic milk was raised to 0.16 mg/ml, corresponding to an activity of 8772.95 mU/ml. High lipoprotein lipase activity led to a significant reduction of triglyceride concentration in milk, but other components were largely unchanged. Normal pups fed with transgenic milk showed inferior growth performances compared to those fed with normal milk. CONCLUSION: Our study suggests a possibility to reduce the triglyceride content of cow milk using transgenic technology.

  12. CUZD1 is a critical mediator of the JAK/STAT5 signaling pathway that controls mammary gland development during pregnancy.

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    Janelle Mapes

    2017-03-01

    Full Text Available In the mammary gland, genetic circuits controlled by estrogen, progesterone, and prolactin, act in concert with pathways regulated by members of the epidermal growth factor family to orchestrate growth and morphogenesis during puberty, pregnancy and lactation. However, the precise mechanisms underlying the crosstalk between the hormonal and growth factor pathways remain poorly understood. We have identified the CUB and zona pellucida-like domain-containing protein 1 (CUZD1, expressed in mammary ductal and alveolar epithelium, as a novel mediator of mammary gland proliferation and differentiation during pregnancy and lactation. Cuzd1-null mice exhibited a striking impairment in mammary ductal branching and alveolar development during pregnancy, resulting in a subsequent defect in lactation. Gene expression profiling of mammary epithelium revealed that CUZD1 regulates the expression of a subset of the EGF family growth factors, epiregulin, neuregulin-1, and epigen, which act in an autocrine fashion to activate ErbB1 and ErbB4 receptors. Proteomic studies further revealed that CUZD1 interacts with a complex containing JAK1/JAK2 and STAT5, downstream transducers of prolactin signaling in the mammary gland. In the absence of CUZD1, STAT5 phosphorylation in the mammary epithelium during alveologenesis was abolished. Conversely, elevated expression of Cuzd1 in mammary epithelial cells stimulated prolactin-induced phosphorylation and nuclear translocation of STAT5. Chromatin immunoprecipitation confirmed co-occupancy of phosphorylated STAT5 and CUZD1 in the regulatory regions of epiregulin, a potential regulator of epithelial proliferation, and whey acidic protein, a marker of epithelial differentiation. Collectively, these findings suggest that CUZD1 plays a critical role in prolactin-induced JAK/STAT5 signaling that controls the expression of key STAT5 target genes involved in mammary epithelial proliferation and differentiation during alveolar

  13. NMR-metabolomics profiling of mammary gland secretory tissue and milk serum in two goat breeds with different levels of tolerance to seasonal weight loss.

    Science.gov (United States)

    Palma, Mariana; Hernández-Castellano, Lorenzo E; Castro, Noemí; Arguëllo, Anastasio; Capote, Juan; Matzapetakis, Manolis; de Almeida, André Martinho

    2016-06-21

    Goats are of special importance in the Mediterranean and tropical regions for producing a variety of dairy products. The scarcity of pastures during the dry season leads to seasonal weight loss (SWL), which affects milk production. In this work, we studied the effect of feed-restriction on two dairy goat breeds, with different tolerance levels to SWL: the Majorera breed (tolerant) and the Palmera breed (susceptible). Nuclear magnetic resonance (NMR) was used to compare the metabolome of an aqueous fraction of the mammary gland and milk serum from both breeds. Goats in mid-lactation were divided by breed, and each in two feed-regime groups: the control group and the restricted-fed group (to achieve 15-20% reduction of body weight at the end of the experiment). Milk and mammary gland samples were collected at the end of the experimental period (23rd day). (1)H NMR spectra were collected from the aqueous extract of the mammary gland biopsies and the milk serum. Profiling analysis has led to the identification of 46 metabolites in the aqueous extract of the mammary gland. Lactose, glutamate, glycine and lactate were found to be the most abundant. Analysis of milk serum allowed the identification of 50 metabolites, the most abundant being lactose, citrate and creatine. Significant differences were observed, in mammary gland biopsies and milk serum, between control and restricted-fed groups in both breeds, albeit with no differences between the breeds. Variations seem to be related to metabolism adaptation to the low-energy diet and are indicative of breed-specific microflora. Milk serum showed more metabolites varying between control and restricted groups, than the mammary gland. The Majorera breed also showed more variations than the Palmera breed in milk samples, which could be an indication of a prompt adaptation to SWL by the Majorera breed.

  14. H-ras oncogene mutations during development of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced rat mammary gland cancer.

    Science.gov (United States)

    Yu, Minshu; Snyderwine, Elizabeth G

    2002-12-01

    Laser capture microdissection, polymerase chain reaction-restriction fragment length polymorphism analysis, and DNA sequencing was used to detect H-ras codon 12 and 13 mutations during the stages of mammary gland cancer development in rats exposed to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogen found in cooked meat. Ten oral doses of PhIP (75 mg/kg, p.o., once per day) were administered to adolescent female Sprague-Dawley rats and mammary glands examined histologically for intraductal proliferations (IDPs), carcinoma in situ and carcinomas 7-14 weeks later. Mammary gland epithelial cells from normal tissue and distinct lesions were collected from glass slides and analyzed for mutations. H-ras codon 12/13 mutations were detected in 73%, 75%, 100%, and 100% of normal mammary glands, IDPs, carcinoma in situ, and carcinoma, respectively, after PhIP treatment. The spectrum of activating mutations included G(35) to A or C base substitution mutations in codon 12, and G(37) to T or A base substitution mutations in codon 13. The spectrum of H-ras mutations was similar among normal mammary gland from PhIP treated rats, preneoplastic lesions, and carcinomas. Furthermore, the spectrum of mutations was consistent with the involvement of PhIP-guanine adduct formation. The results support the notion that mutations in H-ras codons 12 and 13 are largely PhIP-DNA adduct-induced and involved in the initiation and development of mammary gland cancer in rats exposed to PhIP.

  15. Three-dimensional culture system can induce expression of casein in immortalized bovine mammary epithelial cells.

    Science.gov (United States)

    Zhan, Kang; Lin, Miao; Liu, MingMei; Sui, YangNan; Babekir, Haitham Mohammed; Zhao, GuoQi

    2017-05-01

    Primary bovine mammary epithelial cells (BMECs) are not ideal models for long-term studies of lactation mechanisms because these cells in a monolayer culture system cannot be polarized to simulate the physiological functions in vitro. We investigate the effects of different culture models and karyotypes on casein expression in a three-dimensional (3D) culture system. The immortalized cells' karyotypes were analyzed at passages 10, 20, 30 and 40 to detect the effects of chromosome stability. Western blotting examined that whether or not the immortalized cells at passages 5, 10, 20, 30, 40 and 50 could induce expression of casein in a 3D culture system. The proper polarization of the acinar structures was monitored. BMECs were successfully immortalized. The cell karyotype at passage 30 remained at 60 chromosomes and the average value was 57.1 ± 0.40 after passage 40. The polarized protein's levels were up-regulated in 3D culture compared to 2D culture. Expression of αs1, β and κ-casein could be detectable in a passage range in 3D culture. Expression of αs2-casein was undetectable in all experimental groups. However, all casein expressions were barely detectable in traditional 2D culture system. Therefore, 3D culture system is an important tool for the long-term study of lactation mechanisms in vitro. © 2016 Japanese Society of Animal Science.

  16. Tudor-SN Regulates Milk Synthesis and Proliferation of Bovine Mammary Epithelial Cells

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    Jinxia Ao

    2015-12-01

    Full Text Available Tudor staphylococcal nuclease (Tudor-SN is a highly conserved and ubiquitously expressed multifunctional protein, related to multiple and diverse cell type- and species-specific cellular processes. Studies have shown that Tudor-SN is mainly expressed in secretory cells, however knowledge of its role is limited. In our previous work, we found that the protein level of Tudor-SN was upregulated in the nucleus of bovine mammary epithelial cells (BMEC. In this study, we assessed the role of Tudor-SN in milk synthesis and cell proliferation of BMEC. We exploited gene overexpression and silencing methods, and found that Tudor-SN positively regulates milk synthesis and proliferation via Stat5a activation. Both amino acids (methionine and estrogen triggered NFκB1 to bind to the gene promoters of Tudor-SN and Stat5a, and this enhanced the protein level and nuclear localization of Tudor-SN and p-Stat5a. Taken together, these results suggest the key role of Tudor-SN in the transcriptional regulation of milk synthesis and proliferation of BMEC under the stimulation of amino acids and hormones.

  17. Rac1 Controls Both the Secretory Function of the Mammary Gland and Its Remodeling for Successive Gestations.

    Science.gov (United States)

    Akhtar, Nasreen; Li, Weiping; Mironov, Aleksander; Streuli, Charles H

    2016-09-12

    An important feature of the mammary gland is its ability to undergo repeated morphological changes during each reproductive cycle with profound tissue expansion in pregnancy and regression in involution. However, the mechanisms that determine the tissue's cyclic regenerative capacity remain elusive. We have now discovered that Cre-Lox ablation of Rac1 in mammary epithelia causes gross enlargement of the epithelial tree and defective alveolar regeneration in a second pregnancy. Architectural defects arise because loss of Rac1 disrupts clearance in involution following the first lactation. We show that Rac1 is crucial for mammary alveolar epithelia to switch from secretion to a phagocytic mode and rapidly remove dying neighbors. Moreover, Rac1 restricts the extrusion of dying cells into the lumen, thus promoting their eradication by live phagocytic neighbors while within the epithelium. Without Rac1, residual milk and cell corpses flood the ductal network, causing gross dilation, chronic inflammation, and defective future regeneration. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Comparative pathology of mammary gland cancers in domestic and wild animals.

    Science.gov (United States)

    Munson, Linda; Moresco, Anneke

    2007-01-01

    Mammary cancer occurs among all taxonomic groups, and comparing the disease in animals with breast cancer in women could greatly improve our understanding of the relevant risk factors and genetic profiles for this disease. Differences in cancer prevalence between carnivores and herbivores and between captive and wild carnivores are striking and support the hypotheses that diet and reproductive history are major risk factors. Domestic dogs and cats have a high prevalence of mammary tumors, and the majority of tumors in cats are aggressive cancers. Many domestic dogs and cats are prevented from breeding, resulting in their being exposed to recurrent estrogen peaks followed by high persistent levels of progesterone. Therefore progesterone appears to be a significant risk factor for cancer development. Supporting this suspicion is the observation that most mammary cancers in zoo cats are in those treated with the potent synthetic progestin contraceptive, melengestrol acetate. The more common morphologic types of mammary cancer in canids and felids include tubulopapillary, solid, cribriform, comedo and anaplastic carcinomas. Dogs also develop complex carcinomas, which likely evolve from the complex adenomas or mixed tumors that are so common in this species and are promoted by exogenous progesterone treatment. Among zoo felids, jaguars are at higher risk for mammary cancer and also have a high prevalence of ovarian papillarycystadenocarcinomas, a profile similar to women with BRCA1 mutations. As for women, estrogen (ER) and progesterone receptor (PR) expression varies in canine and feline mammary cancers. In general, ER expression is low, but PR expression persists in most cancers. Alterations in molecular controls of cell proliferation or survival in breast cancer, such as cyclin A and p53 expression, have been identified in dog and cat mammary cancers. Overall, spontaneous mammary cancers in cats and dogs make excellent models for human breast cancer, and knowledge of

  19. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity.

    Science.gov (United States)

    Skálová, Alena; Vanecek, Tomas; Sima, Radek; Laco, Jan; Weinreb, Ilan; Perez-Ordonez, Bayardo; Starek, Ivo; Geierova, Marie; Simpson, Roderrick H W; Passador-Santos, Fabricio; Ryska, Ales; Leivo, Ilmo; Kinkor, Zdenek; Michal, Michal

    2010-05-01

    We present a series of 16 salivary gland tumors with histomorphologic and immunohistochemical features reminiscent of secretory carcinoma of the breast. This is a hitherto undescribed and distinctive salivary gland neoplasm, with features resembling both salivary acinic cell carcinoma (AciCC) and low-grade cystadenocarcinoma, and displaying strong similarities to breast secretory carcinoma. Microscopically, the tumors have a lobulated growth pattern and are composed of microcystic and glandular spaces with abundant eosinophilic homogenous or bubbly secretory material positive for periodic acid-Schiff, mucicarmine, MUC1, MUC4, and mammaglobin. The neoplasms also show strong vimentin, S-100 protein, and STAT5a positivity. For this tumor, we propose a designation mammary analogue secretory carcinoma of salivary glands (MASC). The 16 patients comprised 9 men and 7 women, with a mean age of 46 years (range 21 to 75). Thirteen cases occurred in the parotid gland, and one each in the minor salivary glands of the buccal mucosa, upper lip, and palate. The mean size of the tumors was 2.1 cm (range 0.7 to 5.5 cm). The duration of symptoms was recorded in 11 cases and ranged from 2 months to 30 years. Clinical follow-up was available in 13 cases, and ranged from 3 months to 10 years. Four patients suffered local recurrences. Two patients died, 1 of them owing to multiple local recurrences with extension to the temporal bone, and another owing to metastatic dissemination to cervical lymph nodes, pleura, pericardium, and lungs. We have shown a t(12;15) (p13;q25) ETV6-NTRK3 translocation in all but one case of MASC suitable for analysis. One case was not analyzable and another was not available for testing. This translocation was not found in any conventional salivary AciCC (12 cases), nor in other tumor types including pleomorphic adenoma (1 case) and low-grade cribriform cystadenocarcinoma (1 case), whereas ETV6-NTRK3 gene rearrangements were proven in all 3 tested cases of

  20. Prenatal exposure to BPA alters the epigenome of the rat mammary gland and increases the propensity to neoplastic development.

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    Eugen Dhimolea

    Full Text Available Exposure to environmental estrogens (xenoestrogens may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments, with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50. BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene

  1. Appearance of myoepithelial cells in developing rat mammary glands identified with the lectins Griffonia simplicifolia-1 and pokeweed mitogen.

    Science.gov (United States)

    Hughes, C M; Rudland, P S

    1990-11-01

    The histochemical binding of peroxidase-conjugated Griffonia simplicifolia-1 (GS-1) and pokeweed mitogen (PWM) to methacarn-preserved and paraffin-embedded female rat mammary glands at different developmental stages has been undertaken with a view to investigating the ontogeny of the myoepithelial cell. Conjugated GS-1 fails to stain the outer layer of ductal cells in neonatal rats up to 3 days old, but thereafter the staining increases so that all such cells are intensely stained in rats 5 days old and in mature, pregnant, and lactating rats. Conjugated GS-1 also stains most of the inner epithelial cells that line the ducts in neonatal rats up to about 5 days after birth; thereafter no such cells are stained in mature, pregnant, and lactating rats. Conjugated PWM stains both the inner and outer cell layers of ducts in neonatal rats up to 5 days old; thereafter the fraction of strongly stained cells declines rapidly in both cell layers so that in 6-day-old rats only weak staining is visible. Staining with PWM continues to decline for the inner epithelial cells of the ducts until it ceases when the rats mature; in contrast, that for the outer cell layer of the ducts increases so that all such cells are stained intensely when the rats mature. This pattern of ductal staining with PWM is maintained for pregnant and lactating rats. In terminal end buds of mammary ducts of prepubertal rats, GS-1 binds mainly to the peripheral or cap cells, the staining intensity increasing from cap cells at the distal tip to myoepithelial cells of the subtending duct. PWM binds to many more of the cortical epithelial cells and fewer of the cap cells. At the ultrastructural level, cap cells and adjacent immature myoepithelial cells both bind GS-1 and PWM to their surfaces, but basal clear cells do not. In alveolar buds and in alveoli, both conjugated lectins GS-1 and PWM bind to myoepithelial cells but not to epithelial cells of the rat mammary gland. We suggest that the appearance of

  2. Metastasis of Mammary Gland Malignant Phyllodes Tumor to the Mandibular Region: A Case Report and Review of the Literature.

    Science.gov (United States)

    Yoshiba, Sayaka; Saotome, Takashi; Mikogami, Tetsuya; Shirota, Tatsuo

    2017-02-01

    Phyllodes tumor is a rare breast tumor described by Müller (1938) as a lesion comprising leaflike stromal fibrous components and narrow cysts. The frequency of distant metastasis from this entity is reportedly approximately 20%, and no effective therapy has been established, so the prognosis is poor. This report describes the case of a 60-year-old woman with a history of left lung resection who showed metastasis of a mammary gland malignant phyllodes tumor to the oral cavity. Intraoral examination showed an elastic, hard mass measuring 28 × 27 mm in the gingiva around the left mandibular second molar. Biopsy examination showed growth of giant cells and roughly circular cells showing positivity for S-100, p63, and vimentin on immunohistochemical staining. The authors diagnosed metastasis of the mammary gland malignant phyllodes tumor to the left mandible and performed cyber knife irradiation (44 Gy in 5 fractions) of the left mandible. The mass in the oral cavity disappeared after cyber knife irradiation, but the patient died of direct invasion to the spine. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  3. Analysis of lactoferin gene polymophism and its association to milk quality and mammary gland health in Holstein-Friesian cows

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    Maletić Milan

    2013-01-01

    Full Text Available Lactoferrin (LTF is a glycoprotein, a member of transferrin gene family which plays an important role in immune mechanisms in the mammary glands of cows. The amount of lactoferrin increases during inflammatory processes and viral infections. The aim of this investigation was to monitor the distribution of lactoferrin gene genotypes and its connection to milk quality and the occurrence of mammary gland diseases in 46 Holstein-Freisian cows of different age (2-7 years on a farm near Belgrade. DNA was isolated from blood samples, and the polymorphism of lactoferrin gene was deterimined by PCR-RFLP method using the restriction enzyme Eco RI. We found two alelic forms of this gene in cows included in these experiments (A and B and two genotypes (AA and AB in a ratio 71.7% to 28.3%. The genotype BB was not found in this sample. In order to determine the degree of differences between genotypes we used discriminant analysis which has shown that there is a statistically significant difference between genotypes AA and with respect to productive parameters. When analyzed separately, the only parameter which differed significantly (p=0.021 between two genotypes was total milk production. Individuals with observed genotypes are most similar for the amount of milk fat (p=0.271. There is no statistically significant difference in the number of somatic cells in milk samples between the examined genotypes. [Projekat Ministarstva nauke Republike Srbije, br. III46002

  4. The Goat (Capra hircus Mammary Gland Mitochondrial Proteome: A Study on the Effect of Weight Loss Using Blue-Native PAGE and Two-Dimensional Gel Electrophoresis.

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    Graziano Cugno

    Full Text Available Seasonal weight loss (SWL is the most important limitation to animal production in the Tropical and Mediterranean regions, conditioning producer's incomes and the nutritional status of rural communities. It is of importance to produce strategies to oppose adverse effects of SWL. Breeds that have evolved in harsh climates have acquired tolerance to SWL through selection. Most of the factors determining such ability are related to changes in biochemical pathways as affected by SWL. In this study, a gel based proteomics strategy (BN: Blue-Native Page and 2DE: Two-dimensional gel electrophoresis was used to characterize the mitochondrial proteome of the secretory tissue of the goat mammary gland. In addition, we have conducted an investigation of the effects of weight loss in two goat breeds with different levels of adaptation to nutritional stress: Majorera (tolerant and Palmera (susceptible. The study used Majorera and Palmera dairy goats, divided in 4 sets, 2 for each breed: underfed group fed on wheat straw (restricted diet, so their body weight would be 15-20% reduced by the end of experiment, and a control group fed with an energy-balanced diet. At the end of the experimental period (22 days, mammary gland biopsies were obtained for all experimental groups. The proteomic analysis of the mitochondria enabled the resolution of a total of 277 proteins, and 148 (53% were identified by MALDI-TOF/TOF mass spectrometry. Some of the proteins were identified as subunits of the glutamate dehydrogenase complex and the respiratory complexes I, II, IV, V from mitochondria, as well as numerous other proteins with functions in: metabolism, development, localization, cellular organization and biogenesis, biological regulation, response to stimulus, among others, that were mapped in both BN and 2DE gels. The comparative proteomics analysis enabled the identification of several proteins: NADH-ubiquinone oxidoreductase 75 kDa subunit and lamin B1 mitochondrial

  5. Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses.

    Science.gov (United States)

    Paquette, Stéphane G; Banner, David; Huang, Stephen S H; Almansa, Raquel; Leon, Alberto; Xu, Luoling; Bartoszko, Jessica; Kelvin, David J; Kelvin, Alyson A

    2015-10-01

    Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus

  6. Effects of the plant extract silymarin on prolactin concentrations, mammary gland development, and oxidative stress in gestating gilts.

    Science.gov (United States)

    Farmer, C; Lapointe, J; Palin, M-F

    2014-07-01

    lutea of TRT animals when compared with CTL. This is the first demonstration that, in female pigs, silymarin can increase prolactin concentrations and protect against oxidative stress, yet the increase in prolactin was not enough to have beneficial effects on mammary gland development in late gestation.

  7. Scribble modulates the MAPK/Fra1 pathway to disrupt luminal and ductal integrity and suppress tumour formation in the mammary gland.

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    Nathan J Godde

    2014-05-01

    Full Text Available Polarity coordinates cell movement, differentiation, proliferation and apoptosis to build and maintain complex epithelial tissues such as the mammary gland. Loss of polarity and the deregulation of these processes are critical events in malignant progression but precisely how and at which stage polarity loss impacts on mammary development and tumourigenesis is unclear. Scrib is a core polarity regulator and tumour suppressor gene however to date our understanding of Scrib function in the mammary gland has been limited to cell culture and transplantation studies of cell lines. Utilizing a conditional mouse model of Scrib loss we report for the first time that Scrib is essential for mammary duct morphogenesis, mammary progenitor cell fate and maintenance, and we demonstrate a critical and specific role for Scribble in the control of the early steps of breast cancer progression. In particular, Scrib-deficiency significantly induced Fra1 expression and basal progenitor clonogenicity, which resulted in fully penetrant ductal hyperplasia characterized by high cell turnover, MAPK hyperactivity, frank polarity loss with mixing of apical and basolateral membrane constituents and expansion of atypical luminal cells. We also show for the first time a role for Scribble in mammalian spindle orientation with the onset of mammary hyperplasia being associated with aberrant luminal cell spindle orientation and a failure to apoptose during the final stage of duct tubulogenesis. Restoring MAPK/Fra1 to baseline levels prevented Scrib-hyperplasia, whereas persistent Scrib deficiency induced alveolar hyperplasia and increased the incidence, onset and grade of mammary tumours. These findings, based on a definitive genetic mouse model provide fundamental insights into mammary duct maturation and homeostasis and reveal that Scrib loss activates a MAPK/Fra1 pathway that alters mammary progenitor activity to drive premalignancy and accelerate tumour progression.

  8. The effect of low-to-moderate-dose ethanol consumption on rat mammary gland structure and function and early postnatal growth of offspring.

    Science.gov (United States)

    Probyn, Megan E; Lock, Emma-Kate; Anderson, Stephen T; Walton, Sarah; Bertram, John F; Wlodek, Mary E; Moritz, Karen M

    2013-05-15

    High levels of alcohol consumption during pregnancy can lead to growth deficits in early postnatal life. However, the effects of low-to-moderate alcohol consumption during pregnancy are less clearly defined. The aim of this study was to determine whether low-to-moderate ethanol (EtOH) consumption throughout pregnancy in the rat alters maternal mammary gland morphology and milk protein levels, thereby affecting lactation and the growth of pups after birth. Sprague-Dawley rats were fed an ad libitum liquid diet ± 6% vol/vol EtOH throughout pregnancy. Mammary glands from dams were collected at embryonic day (E) 20 or postnatal day (PN) 1, and expression of milk proteins (α-lactalbumin, β-casein, and whey acidic protein) was examined. In addition, relative amounts of alveoli, lactiferous ducts, adipose tissue, and blood vessels were determined at PN1. A subset of rats gave birth, and offspring growth and milk intake were recorded. Mammary gland weight was unaltered by EtOH, and stereological analysis showed no differences in gland structure compared with control. Although there were no significant changes in mammary gland gene expression at the RNA level, protein levels of α-lactalbumin were increased and whey acidic protein were decreased by EtOH. Offspring of EtOH-fed dams consumed less milk than controls in the lactational period; however, this did not alter their early postnatal growth. Overall, it appears that low-to-moderate-dose prenatal EtOH exposure does not significantly alter mammary gland development but may alter the composition of the various proteins found within the milk in a manner that maintains overall pup growth.

  9. Mammary-specific inactivation of E-cadherin and p53 impairs functional gland development and leads to pleomorphic invasive lobular carcinoma in mice

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    Patrick W. B. Derksen

    2011-05-01

    Breast cancer is the most common malignancy in women of the Western world. Even though a large percentage of breast cancer patients show pathological complete remission after standard treatment regimes, approximately 30–40% are non-responsive and ultimately develop metastatic disease. To generate a good preclinical model of invasive breast cancer, we have taken a tissue-specific approach to somatically inactivate p53 and E-cadherin, the cardinal cell-cell adhesion receptor that is strongly associated with tumor invasiveness. In breast cancer, E-cadherin is found mutated or otherwise functionally silenced in invasive lobular carcinoma (ILC, which accounts for 10–15% of all breast cancers. We show that mammary-specific stochastic inactivation of conditional E-cadherin and p53 results in impaired mammary gland function during pregnancy through the induction of anoikis resistance of mammary epithelium, resulting in loss of epithelial organization and a dysfunctional mammary gland. Moreover, combined inactivation of E-cadherin and p53 induced lactation-independent development of invasive and metastatic mammary carcinomas, which showed strong resemblance to human pleomorphic ILC. Dissemination patterns of mouse ILC mimic the human malignancy, showing metastasis to the gastrointestinal tract, peritoneum, lung, lymph nodes and bone. Our results confirm that loss of E-cadherin contributes to both mammary tumor initiation and metastasis, and establish a preclinical mouse model of human ILC that can be used for the development of novel intervention strategies to treat invasive breast cancer.

  10. The effects of endocrine and mechanical stimulation on stage I lactogenesis in bovine mammary epithelial cells.

    Science.gov (United States)

    Stiening, C M; Hoying, J B; Abdallah, M B; Hoying, A M; Pandey, R; Greer, K; Collier, R J

    2008-03-01

    The study objective was to evaluate the effect of endocrine and mechanical (gel release) signaling on bovine mammary epithelial cell ultrastructure and gene expression. Cultures receiving only one stimulus demonstrated partially differentiated ultrastructure, which included abundant polysomes, limited rough endoplasmic reticulum, and absence of secretory products, whereas the 2 stimuli together induced a more complete lactogenic phenotype that included increased rough endoplasmic reticulum, abundant lipid droplets, and secretory vesicles containing casein micelles. The structural data indicated that although synthesis of milk components was initiated, the copious synthesis and secretion associated with stage II lactogenesis was not evident. Microarray analysis revealed that both prolactin and gel release independently regulated several genes linked to a wide array of cellular activities. In combination, they regulated fewer genes targeted to lactogenesis. Genes regulated by the combination treatment included claudin 7, multiple caseins, xanthine oxidoreductase, and several protein synthesis, packaging, and transport genes. Genes related to structural activity including keratin 15 (morphogenesis), alpha-spectrin (cell shape via actin cytoskeleton), and chitinase-like protein 1 (tissue remodeling) were up-regulated by the combination treatment as was the transcription factor Kruppel-like factor 2 (KLF-2). However, Snail 2, which down-regulates and inhibits tight junction components, was repressed in response to the combination treatment. These results suggest coordination between endocrine and physical signals at the genomic level that produces a more specific and targeted transcriptional response associated with stage I lactogenesis. A molecular pathway analysis of the differentially expressed genes revealed that genes regulating cell signaling were linked to those regulating cell structure and adhesion.

  11. Unique Gene Expression Profiles in the Mammary Gland of Prepubertal and Adult Female Rats Treated With Estradiol or Soy Protein Isolate (SPI)

    Science.gov (United States)

    Concerns have arisen regarding infertility and increased breast cancer risk in women consuming soy foods, primarily because of the perceived estrogenicity of soy isoflavones such as genistein and daidzein. Two studies were conducted in mammary gland to determine if consumption of soy products induce...

  12. Unmasking MASC: bringing to light the unique morphologic, immunohistochemical and genetic features of the newly recognized mammary analogue secretory carcinoma of salivary glands.

    Science.gov (United States)

    Bishop, Justin A

    2013-03-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland neoplasm that is characterized by its striking morphologic and molecular similarities to secretory carcinoma of the breast. This review highlights the characteristic clinical, histologic, immunophenotypic, and molecular features of MASC, and draws attention to the differential diagnosis of this increasingly recognized tumor.

  13. The anti-inflammatory and antioxidant effects of melatonin on LPS-stimulated bovine mammary epithelial cells

    OpenAIRE

    Yu, Guang-Min; Kubota, Hirokazu; Okita, Miki; Maeda, Teruo

    2017-01-01

    Mastitis is the most prevalent disease in dairy cattle worldwide and not only causes huge economic losses in the dairy industry but also threatens public health. To evaluate the therapeutic potential of melatonin in mastitis, we examined the ability of melatonin to protect bovine mammary epithelial cells (bMECs) from the harmful effects of lipopolysaccharide (LPS). We found that melatonin inhibited the LPS-binding protein?CD14?TLR4 signaling pathway in bMECs, which had opposing effects on pro...

  14. Serotonin (5-HT affects expression of liver metabolic enzymes and mammary gland glucose transporters during the transition from pregnancy to lactation.

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    Jimena Laporta

    Full Text Available The aim of this experiment was to demonstrate the ability of feeding serotonin (5-HT; 5-hydroxytryptamine precursors to increase 5-HT production during the transition from pregnancy to lactation and the effects this has on maternal energy metabolism in the liver and mammary gland. Pregnant rats (n = 45 were fed one of three diets: I control (CON, II CON supplemented with 0.2% 5-hydroxytryptophan (5-HTP or III CON supplemented with 1.35% L-tryptophan (L-TRP, beginning on d13 of pregnancy through d9 of lactation (d9. Serum (pre and post-partum, milk (daily, liver and mammary gland tissue (d9 were collected. Serum 5-HT was increased in the 5-HTP fed dams beginning on d20 of gestation and remained elevated through d9, while it was only increased on d9 in the L-TRP fed dams. 5-HT levels were increased in mammary gland and liver of both groups. Additionally, 5-HTP fed dams had serum and milk glucose levels similar to the CON, while L-TRP had decreased serum (d9 and milk glucose (all dates evaluated. Feeding 5-HTP resulted in increased mRNA expression of key gluconeogenic and glycolytic enzymes in liver and glucose transporters 1 and 8 (GLUT-1, -8 in the mammary gland. We demonstrated the location of GLUT-8 in the mammary gland both in the epithelial and vascular endothelial cells. Finally, phosphorylated 5' AMP-activated protein kinase (pAMPK, a known regulator of intracellular energy status, was elevated in mammary glands of 5-HTP fed dams. Our results suggest that increasing 5-HT production during the transition from pregnancy to lactation increases mRNA expression of enzymes involved in energy metabolism in the liver, and mRNA abundance and distribution of glucose transporters within the mammary gland. This suggests the possibility that 5-HT may be involved in regulating energy metabolism during the transition from pregnancy to lactation.

  15. Magnetic field exposure increases cell proliferation but does not affect melatonin levels in the mammary gland of female Sprague Dawley rats.

    Science.gov (United States)

    Fedrowitz, Maren; Westermann, Jürgen; Löscher, Wolfgang

    2002-03-01

    In line with the possible relationship between electric power and breast cancer risk as well as the underlying "melatonin hypothesis," we have shown previously (Thun-Battersby et al., Cancer Res., 59: 3627-3633, 1999) that 50-Hz magnetic fields (MFs) of low (100 microTesla) flux density enhance mammary gland tumor development and growth in the 7,12-dimethylbenz(a)anthracene model of breast cancer in female Sprague Dawley rats. On the basis of the melatonin hypothesis and previous observations of induction of ornithine decarboxylase in response to MF, we proposed that the effect of MF exposure on mammary carcinogenesis is related to enhanced proliferation of the mammary epithelium. The objective of the present study was to directly assess this proposal by the use of proliferation markers. Female Sprague Dawley rats were MF or sham exposed for 2 weeks at a flux density of 100 microTesla. Proliferation of epithelial cells in the mammary tissue and adjacent skin was examined by in vivo labeling of proliferating cells with bromodeoxyuridine (BrdUrd) and in situ labeling of the nuclear proliferation-associated Ki-67 protein by the antibody MIB-5. Furthermore, melatonin levels were determined after MF or sham exposure in the pineal gland and directly in the mammary tissue. In additional experiments, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate was used for comparison with the effects of MF exposure. MF exposure significantly enhanced BrdUrd and Ki-67 labeling in the mammary epithelium, indicating a marked increase in cell proliferation. The most pronounced effect on proliferation was seen in the cranial thoracic (or cervical) mammary complexes, in which we previously had seen the most marked effects of MF exposure on mammary carcinogenesis. In contrast to the melatonin hypothesis, melatonin levels in pineal or mammary glands were not affected by MF exposure. Topical application of 12-O-tetradecanoylphorbol-13-acetate increased BrdUrd and Ki-67 labeling in

  16. Effects of niacin and betaine on bovine mammary and uterine cells exposed to thermal shock in vitro.

    Science.gov (United States)

    Xiao, Y; Rungruang, S; Hall, L W; Collier, J L; Dunshea, F R; Collier, R J

    2017-05-01

    The objective of this study was to investigate the direct effects of feed supplements niacin and betaine on the heat shock responses of in vitro cultured cells derived from bovine mammary and uterine tissues. First, we determined the mRNA expression profiles of the niacin receptor (GPR109A) in bovine tissues (liver, skin, uterus, udder, and ovary) and in cells derived from bovine mammary epithelium (mammary alveolar cells, MAC-T; bovine mammary epithelial cells, BMEC) and endometrium (bovine endometrial cells, BEND). We found that GPR109A was distributed in all examined tissues and cells, and the highest expression was in cells from skin and udder. Second, we evaluated the effects of niacin treatment on the mRNA abundance of heat shock proteins 70 and 27 (HSP70 and HSP27) in MAC-T, BMEC, and BEND under thermoneutral conditions and heat stress, and whether these effects were associated with alterations in the mRNA expression of prostaglandin E2 synthesis-related genes, including cyclooxygenase 1 and 2 (COX-1 and COX-2) and microsomal prostaglandin E synthase 1 and 2 (mPGES-1 and mPGES-2). Quantitative PCR data indicated that niacin suppressed HSP70 mRNA expression in BMEC and both HSP70 and HSP27 in BEND under thermoneutral conditions. Only COX-2 expression was downregulated by niacin in BMEC; other prostaglandin E2 synthesis-related genes stayed unaltered in BMEC and BEND. The mRNA abundance of HSP70, COX-1, COX-2, and mPGES-1 were elevated in niacin-treated MAC-T. During heat stress, niacin increased mRNA levels of HSP70 and HSP27 in MAC-T and HSP27 in BEND, but decreased HSP70 in BMEC. Although mPGES-2 was stimulated by niacin in BEND, the mRNA expression of prostaglandin E2 synthesis-related genes were consistent with neither HSP70 nor HSP27 expression patterns in niacin-treated BMEC and MAC-T. These data suggest that the effects of niacin on heat shock protein expression and prostaglandin E2 synthesis were not well coupled in these cells. Finally, we tested the

  17. B-mode ultrasonography of mammary glands of cows, goats and sheep during α- and β-adrenergic agonist and oxytocin administration

    OpenAIRE

    Bruckmaier, Rupert M.; Blum, Jürg W.

    2017-01-01

    Teat and gland cistern of the mammary glands of five dairy cows, five goats and five sheep were scanned in a water bath during α- and β-adrenergic agonist and oxytocin administration. A 5 MHz linear array scanner was used to create vertical cut pictures with the scan plane longitudinally through the teat channel. The i.v. injection of the α-adrenergic agonist phenylephrine (30 μg/kg) induced diminution of the section area through teat and gland cistern by 38±17% on average within 1 min in all...

  18. Maternal consumption of canola oil suppressed mammary gland tumorigenesis in C3(1 TAg mice offspring

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    Hardman W Elaine

    2010-03-01

    Full Text Available Abstract Background Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring. Methods Female SV 129 mice were divided into two groups and placed on diets containing either 10% w/w corn oil (which is 50% n-6 PUFA, control diet or 10% w/w canola oil (which is 20% n-6 PUFA, 10% n-3 PUFA, test diet. After two weeks on the diets the females were bred with homozygous C3(1 TAg transgenic mice. Mother mice consumed the assigned diet throughout gestation and nursing of the offspring. After weaning, all female offspring were maintained on the control diet. Results Compared to offspring of mothers fed the corn oil diet (CO/CO group, offspring of mothers fed the canola oil diet (CA/CO group had significantly fewer mammary glands with tumors throughout the experiment. At 130 days of age, the CA/CO group had significantly fewer tumors per mouse (multiplicity; the tumor incidence (fraction of mice with any tumor and the total tumor weight (per mouse that developed tumor was less than one half that of the CO/CO group. At 170 days of age, the total tumor weight per mouse was significantly less in the CA/CO group and if a tumor developed the rate of tumor growth rate was half that of CO/CO group. These results indicate that maternal consumption of canola oil was associated with delayed appearance of mammary gland tumors and slowed growth of the tumors that developed. Conclusions Substituting canola oil for corn oil is an easy dietary change for people to make; such a change to the maternal diet may decrease risk for breast cancer in the daughter.

  19. Aspiration biopsy of mammary analogue secretory carcinoma of accessory parotid gland: another diagnostic dilemma in matrix-containing tumors of the salivary glands.

    Science.gov (United States)

    Levine, Pascale; Fried, Karen; Krevitt, Lane D; Wang, Beverly; Wenig, Bruce M

    2014-01-01

    Mammary analogue secretory carcinoma (MASC) is a newly described rare salivary gland tumor, which shares morphologic features with acinic cell carcinoma, low-grade cystadenocarcinoma, and secretory carcinoma of the breast. This is the first reported case of MASC of an accessory parotid gland detected by aspiration biopsy with radiologic and histologic correlation in a 34-year-old patient. Sonographically-guided aspiration biopsy showed cytologic features mimicking those of low-grade mucoepidermoid carcinoma, including sheets of bland epithelial cells, dissociated histiocytoid cells with intracytoplasmic mucinous material, and spindle cells lying in a web-like matrix. Histologic sections showed a circumscribed tumor with microcystic spaces lined by bland uniform epithelial cells and containing secretory material. The tumor cells expressed mammaglobin and BRST-2. The cytologic features, differential diagnosis, and pitfalls are discussed. The pathologic stage was pT1N0. The patient showed no evidence of disease at 1 year follow-up. Copyright © 2012 Wiley Periodicals, Inc.

  20. Distribution of obestatin and ghrelin in human tissues: immunoreactive cells in the gastrointestinal tract, pancreas, and mammary glands

    DEFF Research Database (Denmark)

    Grönberg, Malin; Tsolakis, Apostolos V; Magnusson, Linda

    2008-01-01

    Obestatin and ghrelin are two peptides derived from the same prohormone. It is well established that ghrelin is produced by endocrine cells in the gastric mucosa. However, the distribution of human obestatin immunoreactive cells is not thoroughly characterized. A polyclonal antibody...... that specifically recognizes human obestatin was produced. Using this antibody and a commercial antibody vs ghrelin, the distribution of obestatin and ghrelin immunoreactive cells was determined in a panel of human tissues using immunohistochemistry. The two peptides were detected in the mucosa...... of the gastrointestinal tract, from cardia to ileum, and in the pancreatic islets. Interestingly, epithelial cells in the ducts of mammary glands showed distinct immunoreactivity for both ghrelin and obestatin. By double immunofluorescence microscopy, it was shown that all detected cells were immunoreactive for both...

  1. A Geometrically-Constrained Mathematical Model of Mammary Gland Ductal Elongation Reveals Novel Cellular Dynamics within the Terminal End Bud.

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    Ingrid Paine

    2016-04-01

    Full Text Available Mathematics is often used to model biological systems. In mammary gland development, mathematical modeling has been limited to acinar and branching morphogenesis and breast cancer, without reference to normal duct formation. We present a model of ductal elongation that exploits the geometrically-constrained shape of the terminal end bud (TEB, the growing tip of the duct, and incorporates morphometrics, region-specific proliferation and apoptosis rates. Iterative model refinement and behavior analysis, compared with biological data, indicated that the traditional metric of nipple to the ductal front distance, or percent fat pad filled to evaluate ductal elongation rate can be misleading, as it disregards branching events that can reduce its magnitude. Further, model driven investigations of the fates of specific TEB cell types confirmed migration of cap cells into the body cell layer, but showed their subsequent preferential elimination by apoptosis, thus minimizing their contribution to the luminal lineage and the mature duct.

  2. A Geometrically-Constrained Mathematical Model of Mammary Gland Ductal Elongation Reveals Novel Cellular Dynamics within the Terminal End Bud.

    Science.gov (United States)

    Paine, Ingrid; Chauviere, Arnaud; Landua, John; Sreekumar, Amulya; Cristini, Vittorio; Rosen, Jeffrey; Lewis, Michael T

    2016-04-01

    Mathematics is often used to model biological systems. In mammary gland development, mathematical modeling has been limited to acinar and branching morphogenesis and breast cancer, without reference to normal duct formation. We present a model of ductal elongation that exploits the geometrically-constrained shape of the terminal end bud (TEB), the growing tip of the duct, and incorporates morphometrics, region-specific proliferation and apoptosis rates. Iterative model refinement and behavior analysis, compared with biological data, indicated that the traditional metric of nipple to the ductal front distance, or percent fat pad filled to evaluate ductal elongation rate can be misleading, as it disregards branching events that can reduce its magnitude. Further, model driven investigations of the fates of specific TEB cell types confirmed migration of cap cells into the body cell layer, but showed their subsequent preferential elimination by apoptosis, thus minimizing their contribution to the luminal lineage and the mature duct.

  3. Mammary Analogue Secretory Carcinoma of the Parotid Gland: A Third World Country Perspective-A Case Series.

    Science.gov (United States)

    Salat, Huzaifah; Mumtaz, Ramiz; Ikram, Mubasher; Din, Nasir Ud

    2015-01-01

    Mammary analogue secretory carcinoma (MASC) is a recently described pathological entity in major salivary glands, which was first described by Skálová et al. in 2010. Since then only a limited number of case reports/series have been published describing this tumor with the majority of them discussing the genetic and cytoarchitectural aspect of this tumor. Keeping this in view with the lack of clinical correlation with regard to this tumor, we present our approach to management of two such cases which, according to the best of our knowledge, are the first 2 cases presenting in the South Asian continent. Both patients were diagnosed and managed at Aga Khan University Hospital, Karachi, Pakistan.

  4. Mammary Analogue Secretory Carcinoma of the Parotid Gland: A Third World Country Perspective—A Case Series

    Science.gov (United States)

    Salat, Huzaifah; Mumtaz, Ramiz; Ikram, Mubasher; Din, Nasir Ud

    2015-01-01

    Mammary analogue secretory carcinoma (MASC) is a recently described pathological entity in major salivary glands, which was first described by Skálová et al. in 2010. Since then only a limited number of case reports/series have been published describing this tumor with the majority of them discussing the genetic and cytoarchitectural aspect of this tumor. Keeping this in view with the lack of clinical correlation with regard to this tumor, we present our approach to management of two such cases which, according to the best of our knowledge, are the first 2 cases presenting in the South Asian continent. Both patients were diagnosed and managed at Aga Khan University Hospital, Karachi, Pakistan. PMID:26783481

  5. Mammary Analogue Secretory Carcinoma of the Parotid Gland: A Third World Country Perspective—A Case Series

    Directory of Open Access Journals (Sweden)

    Huzaifah Salat

    2015-01-01

    Full Text Available Mammary analogue secretory carcinoma (MASC is a recently described pathological entity in major salivary glands, which was first described by Skálová et al. in 2010. Since then only a limited number of case reports/series have been published describing this tumor with the majority of them discussing the genetic and cytoarchitectural aspect of this tumor. Keeping this in view with the lack of clinical correlation with regard to this tumor, we present our approach to management of two such cases which, according to the best of our knowledge, are the first 2 cases presenting in the South Asian continent. Both patients were diagnosed and managed at Aga Khan University Hospital, Karachi, Pakistan.

  6. Mammary analog secretory carcinoma of the thyroid gland: A primary thyroid adenocarcinoma harboring ETV6–NTRK3 fusion

    Science.gov (United States)

    Dogan, Snjezana; Wang, Lu; Ptashkin, Ryan N; Dawson, Robert R; Shah, Jatin P; Sherman, Eric J; Tuttle, R Michael; Fagin, James A; Klimstra, David S; Katabi, Nora; Ghossein, Ronald A

    2016-01-01

    ETV6–NTRK3 fusion was identified in several cancers including the recently described mammary analog secretory carcinoma (MASC) of the salivary glands and a minority of papillary thyroid carcinomas. We describe three cases of primary MASC of the thyroid gland and provide a detailed clinical and pathological characterization of the tumor morphology, immunoprofile, and genetic background. Immunohistochemistry for PAX8, TTF-1, thyroglobulin, mammaglobin, GCDFP-15, S-100 protein, and p63 was used to define the tumor immunophenotype. Fluorescence in situ hybridization for ETV6 rearrangement was performed in three, and the next-generation sequencing assay MSK-IMPACT™ (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) was performed in two cases. Primary MASC of the thyroid occurred in two women and one man, age 47–72 years. All patients presented with high T stage, infiltrative, locally aggressive tumors with extrathyroidal extension. Two cases were associated with well-differentiated papillary thyroid carcinoma. Histologically, they appeared as low-grade tumors, resembling MASC of the salivary glands and labeled positive for mammaglobin, GCDFP-15, S-100 protein, p63, weakly positive for PAX8, and negative for TTF-1 and thyroglobulin. Fluorescence in situ hybridization revealed ETV6 rearrangement in all cases. In two tested cases MSK-IMPACT™ confirmed the presence of ETV6–NTRK3 gene fusion. Two patients had at least two local recurrences, one was alive with disease, and one was alive and free of disease after 14 and 17 years, respectively. The third patient was alive and free of disease after 2 years. MASC of the thyroid is histologically, immunophenotypically, and genetically similar to its salivary gland counterpart. Thyroid MASC can be associated with a well-differentiated papillary thyroid carcinoma component, supporting follicular cell origin. Clinically, these carcinomas may show frequent recurrences but are associated

  7. Anti-growth action on mouse mammary and prostate glands of a monoclonal antibody to prolactin receptor.

    Science.gov (United States)

    Sissom, J F; Eigenbrodt, M L; Porter, J C

    1988-12-01

    Monoclonal antibody (PrR-7A) against purified PRL receptor was used in the following studies. When PRL receptor was chromatographed on affinity columns containing PrR-7A antibody or monoclonal antibody against hemocyanin, which served as a control, PRL receptor was bound to the column containing PrR-7A antibody, but not to the column containing control antibody. When solubilized PRL receptor was incubated with PrR-7A antibody, the specific binding of the receptor was reduced 52%. Female mice were treated with the carcinogen, 7,12-dimethylbenz[a]anthracene, and during the succeeding 48 weeks were treated weekly with PrR-7A antibody or control antibody. In the control group 13% developed mammary carcinomas, and 16% developed moderate-to-severe intraductal hyperplasia. No mammary carcinomas were found in the mice treated with PrR-7A antibody, and only 8% of the mice had moderate-to-severe intraductal hyperplasia. Male mice made hyperprolactinemic by implanted pituitary glands were treated weekly with PrR-7A or control antibody. After 7 weeks of treatment, the mean weight of the prostates of mice treated with PrR-7A antibody was 8 +/- 1.1 mg (mean +/- SE), and that of mice treated with control antibody was 27 +/- 3.6 mg. Similar differences were seen in the protein and DNA content of the prostates. These results indicate that PrR-7A antibody is directed against PRL receptor and that immunization with this antibody reduces the incidence of PRL-dependent mammary tumors and preneoplastic ductal hyperplasia and prevents PRL-induced hyperplasia of the prostate.

  8. The Effect of Storage Temperature and Time on the Concentrations of Bovine Serum Amyloid A and Its Mammary Associated Isoform

    Directory of Open Access Journals (Sweden)

    Csilla Tóthová

    2012-01-01

    Full Text Available The objective of this study was to evaluate the effect of storage under various conditions on the concentrations of major bovine acute phase protein—serum amyloid A, and its mammary isoform. Blood samples were taken from seven clinically healthy calves, and milk samples from six clinically healthy dairy cows. The harvested blood serum and the milk samples were fractioned into aliquots. One aliquot was analyzed on the day of collection without storage. The second aliquots were stored at 4°C for 1 day, the remaining aliquots were kept frozen at −18°C for 2, 7, 14, and 21 days, and then analyzed. Blood serum was analyzed for serum amyloid A (SAA. The concentrations of mammary isoform of SAA (M-SAA were measured in milk samples. Over time, the concentrations of SAA in serum showed a tendency of significant decrease during storage at −18°C (P<0.01. Similarly, the values of M-SAA decreased significantly in samples maintained at freezer temperatures (P<0.001. In the refrigerated samples, we found non-significantly lower values of SAA, as well as M-SAA. Presented results indicate that the storage temperature and duration may markedly affect the concentrations of bovine SAA and M-SAA.

  9. Aberrant expression of sLex and sLea as candidate prognostic factors for feline mammary gland tumour.

    Science.gov (United States)

    Yoshida, Saori; Yoshida, Kota; Jaroensong, Tassanee; Lee, Soo-Jung; Kamida, Ayako; Saeki, Kohei; Fujita, Naoki; Nishimura, Ryohei; Sasaki, Nobuo; Nakagawa, Takayuki

    2014-04-01

    Expression of the carbohydrate antigens sialyl Lewis x (sLe(x)) and a (sLe(a)) was evaluated in feline mammary gland tumours (FMGT). Immunohistochemical analysis of tissues from 21 FMGT patients and 11 healthy cats revealed significantly higher sLe(x) and sLe(a) antigen expression in adenocarcinoma tissues compared with that of normal mammary tissues (P <0.01). Serum concentration of sLe(x) was evaluated using an enzyme-linked immunosorbent assay and was significantly higher in the 11 FMGT patients (4.71 ± 10.1 U/ml) than the 22 patients with other disease (2.69 ± 1.59 U/ml) (P = 0.03) and the 22 healthy cats (3.71 ± 1.10 U/ml), although the latter difference was not significant. Although the number of cases examined in this study was small, our findings suggest that aberrant expression of sLe antigens may be induced by tumourigenesis in FMGT and that sLe antigens are potential prognostic tumour markers for FMGT.

  10. Regulation and localization of vascular endothelial growth factor within the mammary glands during the transition from late gestation to lactation.

    Science.gov (United States)

    VanKlompenberg, M K; Manjarín, R; Donovan, C E; Trott, J F; Hovey, R C

    2016-01-01

    The vascular network within the developing mammary gland (MG) grows in concert with the epithelium to prepare for lactation, although the mechanisms coordinating this vascular development are unresolved. Vascular endothelial growth factor A (VEGF-A) mediates angiogenesis and vascular permeability in the MG during pregnancy and lactation, where its expression is upregulated by prolactin. Given our previous finding that late-gestational hyperprolactinemia induced by domperidone (DOM) increased subsequent milk yield from gilts, we sought to establish changes in vascular development during late gestation and lactation in the MGs of these pigs and determine whether DOM altered MG angiogenesis and the factors regulating it. Gilts received either no treatment (n = 6) or DOM (n = 6) during late gestation, then had their MG biopsied from late gestation through lactation to assess microvessel density, VEGF-A distribution and messenger RNA expression, and aquaporin (AQP) gene expression. Microvessel density in the MG was unchanged during gestation then increased between days 2 and 21 of lactation (P lactation (P lactation in first-parity gilts and that VEGF-A is a part of the mammary secretome. Although late-gestational hyperprolactinemia increases milk yield, there was no evidence that it altered vascular development. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Presence and distribution of urocortin and corticotrophin-releasing hormone receptors in the bovine thyroid gland.

    Science.gov (United States)

    Squillacioti, C; De Luca, A; Alì, S; Ciarcia, R; Germano, G; Vittoria, A; Mirabella, N

    2014-12-01

    Urocortin (UCN), a 40 amino acid peptide, is a corticotrophin-releasing hormone (CRH)-related peptide. The biological actions of CRH family peptides are mediated via two types of G-protein-coupled receptors, CRH type 1 (CRHR1) and CRH type 2 (CRHR2). The aim of this study was to investigate the expression of UCN, CRHR1 and CRHR2 by immunoprecipitation, Western blot, immunohistochemistry and RT-PCR in the bovine thyroid gland. Immunoprecipitation and Western blot analysis showed that tissue extracts reacted with the anti-UCN, anti-CRHR1 and anti-CRHR2 antibodies. RT-PCR experiments demonstrated that mRNAs of UCN, CRHR1 and CRHR2 were expressed. UCN immunoreactivity (IR) and CRHR2-IR were found in the thyroid follicular and parafollicular cells and CRHR1-IR in the smooth muscle of the blood vessels. These results suggest that a regulatory system exists in the bovine thyroid gland based on UCN, CRHR1 and CRHR2 and that UCN plays a role in the regulation of thyroid physiological functions through an autocrine/paracrine mechanism. © 2013 Blackwell Verlag GmbH.

  12. Comparison of pH and refractometry index with calcium concentrations in preparturient mammary gland secretions of mares.

    Science.gov (United States)

    Korosue, Kenji; Murase, Harutaka; Sato, Fumio; Ishimaru, Mutsuki; Kotoyori, Yasumitsu; Tsujimura, Koji; Nambo, Yasuo

    2013-01-15

    To test the usefulness of measuring pH and refractometry index, compared with measuring calcium carbonate concentration, of preparturient mammary gland secretions for predicting parturition in mares. Evaluation study. 27 pregnant Thoroughbred mares. Preparturient mammary gland secretion samples were obtained once or twice daily 10 days prior to foaling until parturition. The samples were analyzed for calcium carbonate concentration with a water hardness kit (151 samples), pH with pH test paper (222 samples), and refractometry index with a Brix refractometer (214 samples). The sensitivity, specificity, and positive and negative predictive values for each test were calculated for evaluation of predicting parturition. The PPV within 72 hours and the NPV within 24 hours for calcium carbonate concentration determination (standard value set to 400 μg/g) were 93.8% and 98.3%, respectively. The PPV within 72 hours and the NPV within 24 hours for the pH test (standard value set at 6.4) were 97.9% and 99.4%, respectively. The PPV within 72 hours and the NPV within 24 hours for the Brix test (standard value set to 20%) were 73.2% and 96.5%, respectively. Results suggested that the pH test with the standard value set at a pH of 6.4 would be useful in the management of preparturient mares by predicting when mares are not ready to foal. This was accomplished with equal effectiveness of measuring calcium carbonate concentration with a water hardness kit.

  13. Identification of dopamine transporter in bovine pineal gland using [3H]GBR 12935.

    Science.gov (United States)

    Govitrapong, P; Vilaipun, P; Ebadi, M

    2003-08-01

    The mammalian pineal gland contains several neurotransmitters and receptors for amino acids, biogenic amines, and peptides. Some of these, such as D1 and D2 dopamine receptors, have been previously identified and characterized in the bovine pineal gland by our group. As a matter of fact, the density of D1 dopamine receptors in the pineal gland is higher than that of corpus striatum, suggesting that this organ must possess a high affinity dopamine transporter, which has been identified in this study by using [3H]GBR 12935 as a radiological ligand and nomifensine to determine non-specific binding. The association rate of [3H]GBR 12935 binding to the pineal membrane was examined as a function of time. The binding reached equilibrium within 45 min of incubation at 25 degrees C. The specific binding was reversible and saturable. The dissociation time course of the specific [3H]GBR 12935 binding from the bovine pineal membrane was also studied. A half-life (t1/2) of 14-min was obtained. The saturation analysis of the [3H]GBR 12935 binding revealed a dissociation equilibrium constant (Kd) of 6.0 +/- 0.9 nm and a receptor density (Bmax) of 6.9 +/- 0.3 pmol/mg protein, which were comparable with those values obtained from bovine striatum and frontal cortex. In competitive experiments, the concentrations of drugs required to inhibit 50% of the binding (IC50) were in descending order GBR 12909 > GBR 12935 > trans-flupenthixol > nomifensine > cis-flupenthixol > amitriptyline > imipramine > desipramine > dopamine > fluoxetine > fuvoxamine > d-amphetamine. However, nisoxetine, SCH 23390, norepinephrine, and serotonin were unable to displace [3H]GBR binding. These results show that drugs capable of blocking dopamine transporters were effective in displacing [3H]GBR binding; whereas specific norepinephrine and serotonin transporter inhibitors were less effective or ineffective. In addition, the dopamine transporter is ion-dependent as sodium increased [3H]GBR binding in a

  14. The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development.

    Science.gov (United States)

    Naipauer, Julian; Gattelli, Albana; Degese, Maria Sol; Slomiansky, Victoria; Wertheimer, Eva; LaMarre, Jonathan; Castilla, Lucio; Abba, Martin; Kordon, Edith C; Coso, Omar A

    2013-09-01

    Integrins are heterodimeric cell-surface adhesion receptors that play a critical role in tissue development. Characterization of the full-length mRNA encoding the β1 subunit (Itgb1) revealed an alternative functional cleavage and polyadenylation site that yields a new Itgb1 mRNA isoform 578 bp shorter than that previously reported. Using a variety of experimental and bioinformatic approaches, we found that the two Itgb1 isoforms are expressed at different levels in a variety of mouse tissues, including the mammary gland, where they are differentially regulated at successive developmental stages. The longer mRNA species is prevelant during lactation, whereas the shorter is induced after weaning. In 3D cultures, where expression of integrin β1 protein is required for normal formation of acini, experimental blockade of the longer isoform induced enhanced expression of the shorter species which allowed normal morphological mammary differentiation. The short isoform lacks AU-rich motifs and miRNA target sequences that are potentially implicated in the regulation of mRNA stability and translation efficiency. We further determined that the AU-binding protein HuR appears to selectively stabilize the longer isoform in the mammary gland. In summary, the results of the present study identify a new regulatory instance involved in the fine-tuning of Itgb1 expression during mammary gland development and function.

  15. Secretory pathway Ca2+/Mn2+-ATPase isoform 2 and lactation: specific localization of plasmalemmal and secretory pathway Ca2+ pump isoforms in the mammary gland

    Energy Technology Data Exchange (ETDEWEB)

    Faddy, Helen M.; Smart, Chanel E.; Xu, Ren; Lee, Genee Y.; Kenny, Paraic A.; Feng, Mingye; Rao, Rajini; Brown, Melissa A.; Bissell, Mina J.; Roberts-Thomson, Sarah J.; Monteith, Gregory R.

    2008-04-09

    The supply of calcium to the developing neonate via milk is an important physiological process. Until recently the mechanism for the enrichment of milk with calcium was thought to be almost entirely mediated via the secretory pathway. However, recent studies suggest that a specific isoform of the plasma membrane calcium ATPase, PMCA2, is the primary mechanism for calcium transport into milk, highlighting a major role for apical calcium transport. We compared the expression of the recently identified secretory calcium ATPase, SPCA2, and SPCA1, in the mouse mammary gland during different stages of development. SPCA2 levels increased over 35 fold during lactation, while SPCA1 increased only a modest two fold. The potential importance of SPCA2 in lactation was also highlighted by its localization to luminal secretory cells of the mammary gland during lactation, while SPCA1 was expressed throughout the cells of the mammary gland. We also observed major differences in the localization of PMCA2 and PMCA1 during lactation. Using the SCp2 mouse mammary epithelial cell 3D culture model, differences in the sub-cellular distribution of PMCA2 and PMCA1 were clear. These studies highlight the likely specific roles of PMCA2 and SPCA2 in lactation, and link the recently characterized SPCA2 calcium pump to the supply of calcium into milk and the regulation of Golgi resident enzymes important in lactation. They also indicate that calcium transport into milk is a complex interplay between apical and secretory pathways.

  16. trans-10,cis-12-Conjugated Linoleic Acid Affects Expression of Lipogenic Genes in Mammary Glands of Lactating Dairy Goats.

    Science.gov (United States)

    Shi, Huaiping; Zhang, Tianying; Li, Cong; Wang, Jianjue; Huang, Jiangtao; Li, Zhongyang

    2017-11-01

    The molecular mechanisms on milk fat depression (MFD) in response to trans-10,cis-12-conjugated linoleic acid (t10,c12-CLA) supplementation in ruminants were elucidated in this research with dairy goats. A total of 30 2-year-old Xinong Saanen dairy goats [40 ± 5 days in milk (DIM)] at peak lactation stage were assigned to a 3 × 3 Latin square design (14 day treatment period, followed with 14 day washout). Three CLA treatments included (a) control, fed the basal diet only without CLA supplementation; (b) orally supplemented with 8 g/day of lipid-encapsulated CLA (low dose, CLA-1); and (c) orally supplemented with 16 g/day of lipid-encapsulated CLA (high dose, CLA-2). Expression levels of fatty acid metabolism genes in the mammary tissues were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) in three goats on day 1 and the other three goats on day 14 in each group after the discontinuation of CLA treatment in the third experimental period. Dietary supplementation of CLA led to a significant decrease of milk fat compared to the control (p < 0.05). Milk fat concentrations in CLA-1 and CLA-2 groups were 2.74 and 2.42%, respectively, while the milk fat concentration in the control group was 2.99%. Decreases in short- and medium-chain fatty acids (<16 carbons) and increases in unsaturated fatty acids were observed in the CLA-2 group (p < 0.05). The desaturation indexes of C16 and C18 fatty acids were obviously increased (p < 0.01). RT-qPCR results revealed decreases of the mRNA expression levels of SREBF1, PPARG, LPL, CD36, FABP3, ACSL1, FASN, ACACA, DGAT2, TIP47, ADRP, and BTN1A1 genes in mammary glands (p < 0.05) and an increase of the SCD gene because of CLA supplementation (p < 0.05). In conclusion, t10,c12-CLA-induced MFD was possibly the result from the downregulation of genes involved in lipogenesis in goat mammary glands.

  17. Mammary analogue secretory carcinoma of salivary gland origin: an update and expanded morphologic and immunohistochemical spectrum of recently described entity.

    Science.gov (United States)

    Skalova, Alena

    2013-07-01

    Mammary analogue secretory carcinoma of salivary gland origin (MASC) is a recently described tumor with ETV6 translocation. Akin to secretory breast cancer, MASC expresses S-100 protein, mammaglobin, vimentin, and harbors a t(12;15) (p13;q25) translocation which leads to ETV6-NTRK3 fusion product. Histologically, MASC displays a lobulated growth pattern and is often composed of microcystic, tubular, and solid structures with abundant eosinophilic homogeneous or bubbly secretions. Colloid-like secretory material stains positive for periodic acid-Schiff (PAS) with and without diastase and for Alcian blue. The cells of MASC are devoid of PAS-positive secretory zymogen granules. These features help to exclude the most important differential diagnostic considerations, namely acinic cell carcinoma, low-grade cribriform cystadenocarcinoma, cystadenocarcinoma (not otherwise specified), and low-grade mucoepidermoid carcinoma. To date the presence of the ETV6-NTRK3 fusion gene has not been demonstrated in any other salivary gland tumor than MASC. It is likely that MASC is more common than currently recognized and with further studies, the clinical need for molecular studies of the ETV6-NTRK3 fusion may diminish. However, molecular testing is recommended at this time to arrive at the diagnosis of MASC.

  18. A Hormone-responsive 3D Culture Model of the Human Mammary Gland Epithelium.

    Science.gov (United States)

    Speroni, Lucia; Sweeney, Michael F; Sonnenschein, Carlos; Soto, Ana M

    2016-02-07

    The process of mammary epithelial morphogenesis is influenced by hormones. The study of hormone action on the breast epithelium using 2D cultures is limited to cell proliferation and gene expression endpoints. However, in the organism, mammary morphogenesis occurs in a 3D environment. 3D culture systems help bridge the gap between monolayer cell culture (2D) and the complexity of the organism. Herein, we describe a 3D culture model of the human breast epithelium that is suitable to study hormone action. It uses the commercially available hormone-responsive human breast epithelial cell line, T47D, and rat tail collagen type 1 as a matrix. This 3D culture model responds to the main mammotropic hormones: estradiol, progestins and prolactin. The influence of these hormones on epithelial morphogenesis can be observed after 1- or 2-week treatment according to the endpoint. The 3D cultures can be harvested for analysis of epithelial morphogenesis, cell proliferation and gene expression.

  19. [Somatotype of women of the Stavropol region with mammary gland pathology].

    Science.gov (United States)

    Butova, O A; Eremin, V A; Seĭfulina, G V

    2005-01-01

    The aim of this study was to determine the somatotypic characteristics of women living in Stavropol region, both healthy persons and patients with mammary cancer. 105 women of second period of mature age and of eldery age were examined. For somatotype assessment the scheme of V.P. Chtetzov et al. (1979) was used. Age peculiarities of morphological typing were demonstrated that revealed the dominance of athletic type in mature age and mesoplastic type in the elderly one. The analysis of anthropometric parameters of women with oncological pathology in the indicated periods of ontogenesis has demonstrated a predominance of a mesomorphic vector in shaping their somatotype. The marker signs possessing the greatest informative value in mammary cancer patients of a second period of mature age were the low values of thickness of brachial and breast adipose folds. These signs are suggested as criteria for the formation of groups of risk.

  20. BPTF Maintains Chromatin Accessibility and the Self-Renewal Capacity of Mammary Gland Stem Cells

    Directory of Open Access Journals (Sweden)

    Wesley D. Frey

    2017-07-01

    Full Text Available Chromatin remodeling is a key requirement for transcriptional control of cellular differentiation. However, the factors that alter chromatin architecture in mammary stem cells (MaSCs are poorly understood. Here, we show that BPTF, the largest subunit of the NURF chromatin remodeling complex, is essential for MaSC self-renewal and differentiation of mammary epithelial cells (MECs. BPTF depletion arrests cells at a previously undefined stage of epithelial differentiation that is associated with an incapacity to achieve the luminal cell fate. Moreover, genome-wide analysis of DNA accessibility following genetic or chemical inhibition, suggests a role for BPTF in maintaining the open chromatin landscape at enhancers regions in MECs. Collectively, our study implicates BPTF in maintaining the unique epigenetic state of MaSCs.

  1. The Role of Claudin-7 in Mouse Mammary Gland and Tumorigenesis

    Science.gov (United States)

    2004-07-01

    the detection of subclinical mastitis . Br. Wilson. 1994. Cellular immunity to viral antigens limits l-F Idelietd adtow- Vet. J. 128:284-295. viruses...days with minimal inflamma- tory response; however, significant mastitis was observed 12 days after transduction. Adenovirus transduction could also...be used in the virgin animal with little mastitis 3 days after transduction. Transduced mammary epithelial cells maintained normal morphology and

  2. Aluminium chloride promotes tumorigenesis and metastasis in normal murine mammary gland epithelial cells

    OpenAIRE

    Mandriota, Stefano J.; Tenan, Mirna; Ferrari, Paolo; Sappino, Andr??Pascal

    2016-01-01

    Aluminium salts, present in many industrial products of frequent use like antiperspirants, anti?acid drugs, food additives and vaccines, have been incriminated in contributing to the rise in breast cancer incidence in Western societies. However, current experimental evidence supporting this hypothesis is limited. For example, no experimental evidence that aluminium promotes tumorigenesis in cultured mammary epithelial cells exists. We report here that long?term exposure to concentrations of a...

  3. Secretion and mammary gland uptake of prolactin in dairy cows during lactogenesis.

    Science.gov (United States)

    Malven, P V; Head, H H; Collier, R J

    1987-11-01

    Mammary arteriovenous differences of prolactin concentration and net mammary uptake of prolactin from blood were quantified near parturition in 9 dairy cows. Six cows were milked once daily for at least 6 d before parturition, and prepartum lactogenesis occurred in 3 of 6 cows. Prepartum milking 2 or more d before parturition abruptly increased secretion of prolactin into blood, but milkings within 1 d before or after parturition did not increase prolactin secretion. Concentrations of prolactin in whole milk sampled over 8 d before parturition (64.5 ng/ml) were substantially greater than those occurring several days after parturition (19 ng/ml). Milk prolactin concentrations were unaffected by the successful induction of prepartum lactogenesis, which greatly increased prepartum yields of milk (2 to 8 kg/milking). Therefore, the alveolar lumenal content of prolactin was greatest in pregnant cows with prepartum lactogenesis. This enhanced content of intraalveolar prolactin before parturition was associated with an absence of mammary uptake of prolactin immediately prior to ejection of the prolactin-containing milk from the alveoli. However, prolactin uptake was quickly restored to about 2 micrograms/min per half udder shortly after milk ejection. During the prepartum period, an enhanced intraalveolar reservoir of 200 to 400 micrograms prolactin, due to induction of prepartum lactogenesis, appears to saturate temporarily all putative sites for uptake of prolactin from blood.

  4. Mammary carcinoma diagnostics and therapy; Diagnostik und Therapie des Mammakarzinoms

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Uwe; Baum, Friedemann (eds.) [Diagnostisches Brustzentrum Goettingen BZG, Goettingen(Germany)

    2014-11-01

    The book on mammary carcinoma diagnostics and therapy covers the following issues: development, anatomy and physiology of the mammary glands, pathology of benign and malign mammary gland changes, non-imaging diagnostics; mammography; ultrasonic mammography; magnetic resonance tomography of the mammary glands; imaging diagnostics findings; mammary interventions; examination concepts; operative therapy of the mammary carcinoma; chemotherapy of the mammary carcinoma; radio-oncological therapy of the mammary carcinoma; logistics in a medical center for mammary gland diseases; logistics in an interdisciplinary center for mammary diseases; dialogue conduction and psycho-social attendance.

  5. Ultrastructural Characterization of Mammary Analogue Secretory Carcinoma of the Salivary Glands: A Distinct Entity from Acinic Cell Carcinoma?

    Science.gov (United States)

    Guilmette, Julie; Nielsen, Gunnlaugur P; Faquin, William C; Selig, Martin; Nosé, Vânia; Chi, Anthony W S; Sadow, Peter M

    2017-02-13

    Mammary analogue secretory carcinoma (MASC) of the salivary glands is a recently described neoplasm of the salivary glands with a characteristic morphology complemented by a specific cytogenetic translocation and gene rearrangements. Although immunophenotypic and cytogenetic differences allow for a more reliable distinction, ultrastructural features can also provide important information about the relationship between MASC, classic acinic cell carcinoma (AciCC), and AciCC intercalated duct cell-predominant variant. Following approval from the hospital's institutional review board, 7 cases of MASC, 8 cases of classic AciCC, and 4 cases of AciCC intercalated duct cell-predominant variant were retrieved from the pathology files of Massachusetts General Hospital from 2012 to 2015. Electron microscopy was performed using formalin-fixed, paraffin-embedded tissue. Ultrastructural features of all 19 neoplasms of the salivary glands were recorded. The predominant cell-types observed in MASC are those with intercalated/striated duct cell differentiation. These features include prominent invaginations of the cell surface studded with microvilli, and some intra- and intercellular lumina also with a microvillous surface. Classic AciCC dominant cell-type recapitulates acinar cell differentiation. These cells contain large intracytoplasmic zymogen-like granules. AciCC intercalated duct cell-predominant variant showed both cell populations in various proportions with the intercalated/striated duct cell type usually being the dominant one. MASC presents with distinctive ultrastructural features that allows its proper differentiation from classic AciCC. However, significant ultrastructural features overlaps between both AciCC intercalated duct cells-predominant and classic AciCC and MASC. These findings indicate a very close proximity between these tumors.

  6. Diagnostic utility of phosphorylated signal transducer and activator of transcription 5 immunostaining in the diagnosis of mammary analogue secretory carcinoma of the salivary gland: A comparative study of salivary gland cancers.

    Science.gov (United States)

    Kawahara, Akihiko; Taira, Tomoki; Abe, Hideyuki; Takase, Yorihiko; Kurita, Takashi; Sadashima, Eiji; Hattori, Satoshi; Imamura, Ichio; Matsumoto, Shinji; Fujisaki, Hitomi; Sueyoshi, Kazunobu; Akiba, Jun; Kage, Masayoshi

    2015-10-01

    Mammary analogue secretory carcinoma (MASC) with an ETS variant gene 6 (ETV6)-neurotrophic tyrosine kinase receptor type 3 (NTRK3) translocation is a newly described type of salivary gland cancer. It is known that overexpression of signal transducer and activator of transcription 5a (STAT5a) occurs in secretory carcinoma of the breast and MASC, and STAT5a expression may be related to the ETV6-NTRK3 translocation. It was hypothesized that phosphorylated signal transducer and activator of transcription 5 (p-STAT5) might be specifically expressed in MASC of the salivary gland. The expression of p-STAT5 and mammaglobin (MMG) was examined with immunohistochemistry (IHC)/immunocytochemistry (ICC) in tissue sections from 58 salivary gland cancers (8 MASCs and 50 other salivary gland cancers) and in cytological smears from 17 salivary gland cancers (7 MASCs with paired histologic samples and 10 other salivary gland cancers). p-STAT5 IHC was clearly increased in MASC versus normal salivary gland tissue and other salivary gland cancers. p-STAT5 expression was found in 7 of 8 MASCs (87.5%) and in none of the 50 other salivary gland cancers (0%) by IHC. On cytology, p-STAT5 expression was found in all cases of MASC (7 of 7 or 100%) but in none of the 10 other salivary gland cancers (0%) by ICC. The expression rate of MMG by histology and cytology was higher than that of p-STAT5 in the other salivary gland cancers. p-STAT5 might be useful as a detection marker of MASC in the differential diagnosis of salivary gland cancers, and initial screening with p-STAT5 IHC/ICC, combined with auxiliary fluorescence in situ hybridization confirmation, is a reliable, economical approach to identifying MASC of the salivary gland. © 2015 American Cancer Society.

  7. Spontaneously immortalised bovine mammary epithelial cells exhibit a distinct gene expression pattern from the breast cancer cells

    Directory of Open Access Journals (Sweden)

    Li Qianqian

    2010-10-01

    Full Text Available Abstract Background Spontaneous immortalisation of cultured mammary epithelial cells (MECs is an extremely rare event, and the molecular mechanism behind spontaneous immortalisation of MECs is unclear. Here, we report the establishment of a spontaneously immortalised bovine mammary epithelial cell line (BME65Cs and the changes in gene expression associated with BME65Cs cells. Results BME65Cs cells maintain the general characteristics of normal mammary epithelial cells in morphology, karyotype and immunohistochemistry, and are accompanied by the activation of endogenous bTERT (bovine Telomerase Reverse Transcriptase and stabilisation of the telomere. Currently, BME65Cs cells have been passed for more than 220 generations, and these cells exhibit non-malignant transformation. The expression of multiple genes was investigated in BME65Cs cells, senescent BMECs (bovine MECs cells, early passage BMECs cells and MCF-7 cells (a human breast cancer cell line. In comparison with early passage BMECs cells, the expression of senescence-relevant apoptosis-related gene were significantly changed in BME65Cs cells. P16INK4a was downregulated, p53 was low expressed and Bax/Bcl-2 ratio was reversed. Moreover, a slight upregulation of the oncogene c-Myc, along with an undetectable level of breast tumor-related gene Bag-1 and TRPS-1, was observed in BME65Cs cells while these genes are all highly expressed in MCF-7. In addition, DNMT1 is upregulated in BME65Cs. These results suggest that the inhibition of both senescence and mitochondrial apoptosis signalling pathways contribute to the immortality of BME65Cs cells. The expression of p53 and p16INK4a in BME65Cs was altered in the pattern of down-regulation but not "loss", suggesting that this spontaneous immortalization is possibly initiated by other mechanism rather than gene mutation of p53 or p16INK4a. Conclusions Spontaneously immortalised BME65Cs cells maintain many characteristics of normal BMEC cells and

  8. Determination of the functional size of oxytocin receptors in plasma membranes from mammary gland and uterine myometrium of the rat by radiation inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Soloff, M.S.; Beauregard, G.; Potier, M.

    1988-05-01

    Gel filtration of detergent-solubilized oxytocin (OT) receptors in plasma membrane fractions from both regressed mammary gland and labor myometrium of the rat, showed that specific (/sup 3/H)OT binding was associated with a heterogeneously sized population of macromolecules. As radiation inactivation is the only method available to measure the apparent molecular weights of membrane proteins in situ, we used this approach to define the functional sizes of OT receptors. The results indicate that both mammary and myometrial receptors are uniform in size and of similar molecular mass. Mammary and myometrial receptors were estimated to be 57.5 +/- 3.8 (SD) and 58.8 +/- 1.6 kilodaltons, respectively. Knowledge of the functional size of OT receptors will be useful in studies involving the purification and characterization of the receptor and associated membrane components.

  9. A mouse model to study the effects of hormone replacement therapy on normal mammary gland during menopause: enhanced proliferative response to estrogen in late postmenopausal mice.

    Science.gov (United States)

    Raafat, A M; Hofseth, L J; Li, S; Bennett, J M; Haslam, S Z

    1999-06-01

    Hormone replacement therapy (HRT) with estrogen alleviates menopausal symptoms and is effective in reducing osteoporosis and cardiovascular disease when taken in early postmenopause. Older, late postmenopausal women who never previously received HRT are also believed to benefit from estrogen treatment. On the other hand, increased lifetime exposure of the mammary gland to estrogen may increase the risk of breast cancer. The development of suitable experimental animal model systems can advance our understanding of the effects of estrogen and the timing of HRT on the postmenopausal breast. Toward this end, early and late postmenopausal states were induced in mice by short vs. long term ovariectomy (1 vs. 5 weeks), and the effects of 17beta-estradiol (E) on mammary gland morphology, cell proliferation, and progesterone receptor (PR) levels were investigated. We report that in late postmenopausal mice, E caused a pronounced enlargement of duct ends and 6.5- and 4-fold greater mitogenic responses in the duct end epithelium and adjacent stromal cells, respectively, compared with the response in early postmenopausal mice. Furthermore, after long term, daily treatment with E, steady state levels of proliferation remained 2-fold higher than those of similarly treated, early postmenopausal mice. E failed to increase mammary PR levels in late postmenopausal, but not in early postmenopausal mice. Stimulation of duct ends by E and lack of PR inducibility are characteristics of the immature pubertal mammary gland and indicate that the late postmenopausal mammary gland resembled the immature state. In contrast, minimal E-induced proliferation and increased PR inducibility, characteristics of the adult, sexually mature mammary gland, were retained in early postmenopausal mice. The lack of difference in the numbers of estrogen receptor-positive epithelial or stromal cells or in estrogen receptor cellular concentration after short vs. long term ovariectomy indicates that the

  10. Evaluation of antioxidant and proinflammatory gene expression in bovine mammary tissue during the periparturient period

    National Research Council Canada - National Science Library

    Aitken, S. L; Karcher, E. L; Rezamand, P; Gandy, J. C; VandeHaar, M. J; Capuco, A. V; Sordillo, L. M

    2009-01-01

    * Department of Large Animal Clinical Sciences, and Department of Animal Science, Michigan State University, East Lansing 48824 Bovine Functional Genomics Laboratory, USDA, ARS, Beltsville, MD 20705 1...

  11. Data describing lack of effects of 17α-ethinyl estradiol on mammary gland morphology in female mice exposed during pregnancy and lactation

    Directory of Open Access Journals (Sweden)

    Charlotte D. LaPlante

    2017-10-01

    Full Text Available Ethinyl estradiol (EE is a synthetic estrogen used in pharmaceutical contraceptives. In many studies evaluating estrogenic endocrine disruptors, EE is used as a positive control for estrogenicity. However, the effects of EE often differ from the effects of other xenoestrogens, suggesting that these other compounds might act via distinct mechanisms. Reported here are data describing the effect of low doses of EE during pregnancy and lactation on the morphology of the lactating mammary gland in CD-1 mice. The data suggest that these low doses have few if any discernable effects on mammary gland morphology. Alterations to cell proliferation and the expression of estrogen receptor (ERα were also not observed. These companion data were collected from the same females analyzed for effects of EE on maternal behavior and brain recently published in Reproductive Toxicology (Catanese & Vandenberg, 2017.

  12. In Utero Exposure to Cadmium, Mammary Gland Development, and Breast Cancer Risk

    Science.gov (United States)

    2008-05-01

    34Response of sugarcane to increasing concentrations of copper and cadmium and expression of metallothionein genes." J Plant Physiol 164(11): 1499-515...expression (2nd gland). Tissue collected for immunohistochemistry was fixed in 10% formalin, washed in PBS, dehydrated in 70% ethanol , and paraffin

  13. The housekeeping gene xanthine oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland

    Science.gov (United States)

    Vorbach, Claudia; Scriven, Alistair; Capecchi, Mario R.

    2002-01-01

    Xanthine oxidoreductase (XOR) is the rate-limiting enzyme in purine catabolism occurring in most cell types. However, this housekeeping gene is expressed at very high levels in a number of mammalian tissues including the lactating mammary epithelium, suggesting additional roles for XOR in these tissues. Mice with targeted disruption of XOR were generated to assess these potential additional roles. XOR−/− mice are runted and do not live beyond 6 wk of age. Strikingly, however, XOR+/− females, although of healthy appearance and normal fertility, are unable to maintain lactation and their pups die of starvation 2 wk postpartum. Histological and whole-mount analyses showed that in XOR+/− females the mammary epithelium collapses, resulting in premature involution of the mammary gland. Electron microscopy showed that XOR is specifically required for enveloping milk fat droplets with the apical plasma membrane prior to secretion from the lactating mammary gland. We present evidence that XOR may have primarily a structural role, as a membrane-associated protein, in milk fat droplet secretion and thus XOR provides another example of “gene sharing”. About 5% of women experience primary lactation insufficiency. The above observations suggest that human females suffering from xanthinuria, a deficiency in XOR, are potential candidates for lactation problems. PMID:12502743

  14. Contrast Enhancement in Breast Cancer and Background Mammary-Gland Tissue During the Super-Early Phase of Dynamic Breast Magnetic Resonance Imaging.

    Science.gov (United States)

    Tomida, Tetsuya; Urikura, Atsushi; Uematsu, Takayoshi; Shirata, Kensei; Nakaya, Yoshihiro

    2017-11-01

    We aimed to compare the contrast enhancement between tumor and mammary-gland tissue to distinguish lesions in the super-early phase, during which minimal contrast media uptake is observed in mammary-gland tissue. Dynamic magnetic resonance imaging, including the super-early phase with bolus tracking (BT) method (to determine the optimal imaging start time), was performed by using identical parameters to obtain transverse fat-suppressed T1-weighted images of both breasts. The percent enhancement (PE) and the contrast ratio (CR) indicators for tumor and mammary-gland tissue were assessed in each dynamic phase. The PE values of the tumor were 62.4% and 151.6%, and those of the mammary gland were 0.3% and 20.7% in the super-early and early phases, respectively. Therefore, virtually no background parenchymal enhancement was observed in the super-early phase. The variation in the PE values during the super-early phase was significantly smaller when the values were determined with the BT method (P cancer cases than in noninvasive cancer cases (P imaging start time was observed for the anatomic side factor by the BT method. Background parenchymal enhancement almost never appeared in the super-early phase, but the CR was lower in the super-early phase than in the early phase. The BT method allowed for an optimal imaging start time for the super-early phase and yielded images with less deviation of contrast enhancement. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  15. Combining web-based tools for transparent evaluation of data for risk assessment: developmental effects of bisphenol A on the mammary gland as a case study.

    Science.gov (United States)

    Molander, Linda; Hanberg, Annika; Rudén, Christina; Ågerstrand, Marlene; Beronius, Anna

    2017-03-01

    Different tools have been developed that facilitate systematic and transparent evaluation and handling of toxicity data in the risk assessment process. The present paper sets out to explore the combined use of two web-based tools for study evaluation and identification of reliable data relevant to health risk assessment. For this purpose, a case study was performed using in vivo toxicity studies investigating low-dose effects of bisphenol A on mammary gland development. The reliability of the mammary gland studies was evaluated using the Science in Risk Assessment and Policy (SciRAP) criteria for toxicity studies. The Health Assessment Workspace Collaborative (HAWC) was used for characterizing and visualizing the mammary gland data in terms of type of effects investigated and reported, and the distribution of these effects within the dose interval. It was then investigated whether there was any relationship between study reliability and the type of effects reported and/or their distribution in the dose interval. The combination of the SciRAP and HAWC tools allowed for transparent evaluation and visualization of the studies investigating developmental effects of BPA on the mammary gland. The use of these tools showed that there were no apparent differences in the type of effects and their distribution in the dose interval between the five studies assessed as most reliable and the whole data set. Combining the SciRAP and HAWC tools was found to be a useful approach for evaluating in vivo toxicity studies and identifying reliable and sensitive information relevant to regulatory risk assessment of chemicals. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. The Dietary Protein/Carbohydrate Ratio Differentially Modifies Lipogenesis and Protein Synthesis in the Mammary Gland, Liver and Adipose Tissue during Gestation and Lactation

    Science.gov (United States)

    Velázquez-Villegas, Laura A.; Tovar, Armando R.; López-Barradas, Adriana M.; Torres, Nimbe

    2013-01-01

    During gestation and lactation, a series of metabolic changes that are affected by the diet occurs in various organs of the mother. However, little is known about how the dietary protein (DP)/carbohydrate (DCH) ratio regulates the expression of metabolic genes in the mother. Therefore, the purpose of this work was to study the effect of consuming different percentages of DP/DCH, specifically 10/73, 20/63 and 30/53%, on the expression of genes involved in lipogenesis and protein synthesis in the mammary gland, liver and adipose tissue during gestation and lactation in dams. While the amount of weight gained during gestation was similar for all groups, only dams fed with 30/53% DP/DCH maintained their weight during lactation. In the mammary gland, the expression of the genes involved in lipogenesis, specifically SREBP1 and FAS, was dramatically increased, and the expression of the genes involved in protein synthesis, such as mTOR1, and the phosphorylation of its target protein, S6K, were also increased throughout pregnancy and lactation, regardless of the concentration of DP/DCH. In the liver and adipose tissue, the expression of the genes and proteins involved in lipid metabolism was dependent on the proportion of DP/DCH. The consumption of a low-protein/high-carbohydrate diet increased the expression of lipogenic genes in the liver and adipose tissue and the amount of lipid deposition in the liver. Conversely, the consumption of a high-protein/low-carbohydrate diet increased the expression of genes involved in amino acid oxidation in the liver during gestation. The metabolic adaptations reflected by the changes in the expression of metabolic genes indicate that the mammary gland has a priority for milk synthesis, whereas the adaptations in the liver and adipose tissue are responsible for providing nutrients to the mammary gland to sustain milk synthesis. PMID:23874950

  17. Effects of niacin on Staphylococcus aureus internalization into bovine mammary epithelial cells by modulating NF-κB activation.

    Science.gov (United States)

    Wei, Zhengkai; Fu, Yunhe; Zhou, Ershun; Tian, Yuan; Yao, Minjun; Li, Yimeng; Yang, Zhengtao; Cao, Yongguo

    2014-01-01

    Niacin is a precursor of coenzymes NAD and NADP and plays a critical role in electron transfer during the metabolic process. In addition to its nutrimental function, niacin has long been used for the treatment of lipid disorders and cardiovascular disease. However, the effect of niacin on Staphylococcus aureus (S. aureus) internalization into bovine mammary epithelial cells (bMEC) remains unclear. Here we sought to examine the effect of niacin on S. aureus internalization into bovine mammary epithelial cells (bMEC) and to investigate the potential mechanism. In this study, the growth of S. aureus supplemented with niacin (0.5-2 mM) was monitored turbidimetrically at 600 nm for 24 h and cell viability was measured by MTT assay. Gentamicin protection assay was carried out to determine the effect of niacin on S. aureus internalization into bMEC. To determine the potential mechanism, tracheal antimicrobial peptide (TAP) and β-defensin (BNBD5) expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The activation of nuclear factor-kappa B (NF-κB) was determined by Western blotting. The results showed that niacin (0.5-2 mM) did not affect S. aureus growth and bMEC viability, whereas it inhibits S. aureus internalization ranging from 13% to 42% and down-regulated the mRNA expression of TAP and BNBD5 compared to the control group. No exactly relationship was discovered between S. aureus internalization into bMEC and antimicrobial peptide expression, while niacin inhibited S. aureus-induced NF-κB activation in a dose manner. These dates suggest that inhibiting NF-κB activation may be the potential mechanism of niacin on modulating S. aureus internalization into bMEC. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Bovine-associated mucoprotein: de novo synthesis by nonmammary tissues.

    Science.gov (United States)

    Pringnitz, D J; Butler, J E

    1985-08-01

    Bovine tissues were cultured in vitro in the presence of carbon-14 amino acids and tritiated hexosamine to examine the de novo synthesis of the milk fat globule glycoprotein bovine-associated mucoprotein, by selected tissues. Among tissues examined, the relative synthesis of bovine-associated mucoprotein was highest in mammary tissue. The de novo synthesized bovine-associated mucoprotein in mammary and lacrimal gland cultures when examined for incorporation of carbon-14, had similar sedimentation profiles in sucrose density gradients and incorporated the same relative amount of carbohydrate. The bovine-associated mucoprotein synthesized by lung and spleen cultures sedimented in similar fashion to mammary gland bovine-associated mucoprotein when incorporation of carbon-14 was used as the marker, but it displayed greater heterogeneity when evaluated for tritium incorporation. Bovine-associated mucoprotein in the lung and spleen incorporated relatively less carbohydrate than that synthesized by mammary tissue. These findings support the concept of intertissue heterogeneity, which had been suggested by previous studies.

  19. Immune competence of the mammary gland as affected by somatic cell and pathogenic bacteria in ewes with subclinical mastitis.

    Science.gov (United States)

    Albenzio, M; Santillo, A; Caroprese, M; Ruggieri, D; Ciliberti, M; Sevi, A

    2012-07-01

    Immune competence of the ewe mammary gland was investigated by monitoring the leukocyte differential count, cytokine pattern, and endogenous proteolytic enzymes in milk samples with different somatic cell counts (SCC) and pathogenic bacteria. Furthermore, the leukocyte differential count and T-lymphocyte populations were evaluated in ewe blood. A total of 1,500 individual milk samples were randomly selected from the pool of the samples collected during sampling and grouped into 5 classes of 300 samples each, on the basis of SCC. Classes were 2,000,000 cells/mL. Microbiological analyses of ewe milk were conducted to detect mastitis-related pathogens. Sheep whose udders were without clinical abnormalities, and whose milk was apparently normal but with at least 10(3)cfu/mL of the same pathogen were considered to have subclinical mastitis and therefore defined as infected. Polymorphonuclear neutrophilic leukocytes (PMNL) and macrophages increased with SCC, whereas lymphocytes decreased. Milk samples with SCC >1,000,000 cells/mL showed differences in leukocyte populations between uninfected and infected ewes, with higher percentages of PMNL and macrophages and lower percentages of lymphocytes in infected animals. Nonviable PMNL levels were the highest in ewe milk samples with SCC 500,000 cells/mL, nonviable PMNL were higher in uninfected ewes than in infected ones. In infected animals giving milk with SCC >1,000,000 cells/mL, a higher CD4(+)/CD8(+) ratio was observed, suggesting that the presence of pathogens induced an activation of both CD4(+) and CD8(+). The levels of tumor necrosis factor-α and IL-12 were higher in infected than uninfected ewes, irrespective of SCC. Plasmin activity increased along with SCC and was always higher in infected than uninfected animals; cathepsin D increased starting from 1,001,000 cells/mL in milk samples from noninfected ewes and starting from 301,000 cells/mL in milk samples from infected animals. The associations between somatic

  20. The goat (Capra hircus) mammary gland secretory tissue proteome as influenced by weight loss: A study using label free proteomics.

    Science.gov (United States)

    Hernández-Castellano, Lorenzo E; Ferreira, Ana M; Nanni, Paolo; Grossmann, Jonas; Argüello, Anastasio; Capote, Juan; Cai, Guohong; Lippolis, John; Castro, Noemí; de Almeida, Andre M

    2016-08-11

    Seasonal weight loss (SWL) is a significant limitation to animal production. Breeds that have evolved in harsh climates have acquired tolerance to SWL through selection. Herein, label free proteomics was used to characterize the effects of SWL in two goat breeds with different levels of adaptation to nutritional stress: Majorera (tolerant) and Palmera (susceptible). Nine Majorera and 10 Palmera dairy goats were used, divided in 4 sets, 2 for each breed: underfed and a control group: Majorera Control (MC), Palmera Control (PC), Majorera Restricted (ME) and Palmera Restricted (PE). At day 22, mammary gland biopsy samples were obtained. Label free proteomic analysis enabled the identification of over 1000 proteins, of which 96 showed differential expression between two of the groups within studied comparisons. Majorera breed showed higher expression of immune system related proteins. In contrast, Palmera breed showed higher expression of proteins related to apoptosis. Results indicate that the two goat breeds have a distinct metabolism reaction to SWL, and that proteins related to the immune system and apoptosis such as cadherin-13, collagen alpha-1, nidogen-2, clusterin and protein s100-A8 could be considered putative candidates as markers of tolerance to SWL. Seasonal weight loss (SWL) is one of the major constraints to animal production in the tropics. We compared the proteomics profiles of two dairy goat breeds with different levels of tolerance to SWL under control and feed restriction conditions using label free proteomics. We have identified over 1000 proteins in the goat mammary gland, of which 96 showed differential expression. Despite the fact that both breeds showed a decrease in the number of proteins related to protein, carbohydrates and fat biosynthesis, the tolerant breed showed higher expression of immune system related proteins compared to the susceptible breed. On the contrary, the susceptible breed had higher expression of apoptosis related proteins

  1. Mammary analog secretory carcinoma of the parotid gland: A case report and literature review.

    Directory of Open Access Journals (Sweden)

    Ricardo Balanzá

    2015-01-01

    Conclusion: The presence of t(12;15 (p13;q25 translocation which results in the ETV6-NTRK3 gene fusion or positive immunochemical studies for STAT5, mammoglobin and S100 protein, are necessary to confirm the diagnosis of MASC. MASC treatment should mimic the management of other low-grade malignant salivary gland neoplasms. The inhibition of ETV6-NTRK3 gene fusion could be used as treatment in the future.

  2. Cytological features of mammary analogue secretory carcinoma of salivary gland: fine-needle aspiration of seven cases.

    Science.gov (United States)

    Higuchi, Kayoko; Urano, Makoto; Takahashi, Reisuke H; Oshiro, Hisashi; Matsubayashi, Jun; Nagai, Takeshi; Obikane, Hiyo; Shimojo, Hisashi; Nagao, Toshitaka

    2014-10-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland neoplasm that is defined by ETV6-NTRK3 gene fusion. There have been few case reports on the cytopathologic features of MASC to date. We examined the clinicopathological and cytological features of seven cases of MASC defined by RT-PCR analysis of the ETV6-NTRK3 fusion gene. The cases occurred in three men and four women aged between 39 and 68 years, with a mean of 51.6 years. In five of these seven cases, the tumor involved the parotid gland. Histologically, all cases displayed predominantly microcystic patterns, often a mixture of follicular and papillary-cystic structures. All tumors were immunoreactive for mammaglobin, S-100 protein, and vimentin. Available fine-needle aspiration cytology smears were cellular and exhibited many loosely cohesive syncytial clusters or isolated cells. Many histiocytes, some of which contained hemosiderin pigments, and variously shaped mucinous material were evident in the background or within the epithelial clusters. The majority of cases showed small to medium-sized follicular structures with secreted materials. Papillary clusters were occasionally found. Tumor cells exhibited small to medium-sized round to oval nuclei, with a smooth contour and indistinct or small nucleoli, and vacuolated cytoplasm. No tumor cells had obvious intracytoplasmic zymogen granules. It appeared that clusters of small to medium-sized follicular and papillary configurations consisting of bland tumor cells with vacuolated cytoplasm, but lack of intracytoplasmic zymogen granules, in a mucinous or hemosiderin-laden histiocyte-rich background, were a characteristic cytological feature highly suggestive of MASC. © 2014 Wiley Periodicals, Inc.

  3. Spontaneous basaloid adenomas of the mammary gland in four dogs: clinicopathologic and immunohistochemical features.

    Science.gov (United States)

    Martín de las Mulas, E; Ordás, J; Millán, M Y; Espinosa de los Monteros, A; Reymundo, C

    2002-11-01

    Spontaneous basaloid adenomas occurred in four out of 354 dogs with mammary tumors. Affected dogs were pure-bred, intact females between 6 and 8 years of age. Three dogs were nuliparous, two had pseudopregnancies, and none had received contraceptive steroids. The tumors were multiple (three cases) or unique, less than 1 cm in diameter, well delineated, and composed of uniform cords and clusters of monomorphic epithelial cells with focal signs of squamous or glandular differentiation. A basal cell immunophenotype (cytokeratins 5 and 14 positive) without either glandular epithelial (cytokeratins 8, 18, and 19 negative) or myoepithelial (calponin negative) differentiation was observed in the majority of tumor cells. No recurrence or metastasis was recorded after follow-up periods between 3 and 24 months. In spite of the hormone-dependent nature of this tumor in female Beagles given experimental contraceptive steroids, spontaneous basaloid adenomas lacked estrogen receptor alpha and progesterone receptors.

  4. Genomic study of the mammary gland in bovines acclimated to a ...

    African Journals Online (AJOL)

    Daniela

    2016-02-06

    Feb 6, 2016 ... Consortium (http://nbfgc.msu.edu). The microarrays integrated 4608 Bos taurus and other species genes. (e.g. Homo sapiens) with BLAST sequence information known for Bos taurus. Three biological replicates were used for each experimental group and each replicate included a two-animal RNA pool.

  5. Nutritional regulation of stearoyl-CoA desaturase in the bovine mammary gland

    NARCIS (Netherlands)

    Jacobs, A.A.A.

    2011-01-01

    Increasing the proportion of unsaturated fatty acids (UFA) in milk is believed to be beneficial in terms of human health, thereby increasing the nutritional quality of milk. The proportion of UFA in milk is mainly dependent on the proportion of UFA in the diet, the degree of biohydrogenation of UFA

  6. Mammary analog secretory carcinoma of salivary gland with high-grade histology arising in hard palate, report of a case and review of literature

    Science.gov (United States)

    Luo, Wenyi; Lindley, Sarah W; Lindley, Peter H; Krempl, Gregory A; Seethala, Raja R; Fung, Kar-Ming

    2014-01-01

    Mammary gland analog secretary carcinoma (MASC) of salivary gland is typically a tumor of low histologic grade and behaves as a low-grade malignancy with relatively benign course. This tumor shares histologic features, immunohistochemical profile, and a highly specific genetic translocation, ETV6-NTRK3, with secretory carcinoma of breast. Histologically, it is often mistaken as acinic cell carcinoma, adenocarcinoma not otherwise specified, and other primary salivary gland tumors. Here we report a case of MASC with high-grade transformation and cervical lymph node metastases confirmed with ETV6-NTRK3 translocation arising in the hard palate of a 41 year-old adult. Interestingly, the metastatic carcinoma has lower grade than the original tumor which strongly support malignant transformation of the original tumor. Most commonly, MASC arises from the parotid gland and less often in minor salivary glands. Metastasis is relatively uncommon and high-grade histology has only been reported in four cases with three of them arising from the parotid gland and the location of the fourth one has not been reported. This is the first case with high grade histology that arise from minor salivary gland and it emphasizes the importance of molecular screening of salivary gland tumor with high-grade histology for ETV6-NTRK3 translocation. In our literature of 115 cases that includes the current case, MASC occurred predominantly in adult with only a few cases under 18 years of age and a male to female ratio of 1.2:1. Parotid gland is more commonly affected but there is also significant occurrence in minor salivary glands. Except for the cases with high grade histology, the overall prognosis is good. PMID:25674280

  7. Thymol inhibits Staphylococcus aureus internalization into bovine mammary epithelial cells by inhibiting NF-κB activation.

    Science.gov (United States)

    Wei, Zhengkai; Zhou, Ershun; Guo, Changming; Fu, Yunhe; Yu, Yuqiang; Li, Yimeng; Yao, Minjun; Zhang, Naisheng; Yang, Zhengtao

    2014-01-01

    Bovine mastitis is one of the most costly and prevalent diseases in the dairy industry and is characterised by inflammatory and infectious processes. Staphylococcus aureus (S. aureus), a Gram-positive organism, is a frequent cause of subclinical, chronic mastitis. Thymol, a monocyclic monoterpene compound isolated from Thymus vulgaris, has been reported to have antibacterial properties. However, the effect of thymol on S. aureus internalization into bovine mammary epithelial cells (bMEC) has not been investigated. In this study, we evaluated the effect of thymol on S. aureus internalization into bMEC, the expression of tracheal antimicrobial peptide (TAP) and β-defensin (BNBD5), and the inhibition of NF-κB activation in bMEC infected with S. aureus. Our results showed that thymol (16-64 μg/ml) could reduce the internalization of S. aureus into bMEC and down-regulate the mRNA expression of TAP and BNBD5 in bMEC infected with S. aureus. In addition, thymol was found to inhibit S. aureus-induced nitric oxide (NO) production in bMEC and suppress S. aureus-induced NF-κB activation in a dose-dependent manner. In conclusion, these results indicated that thymol inhibits S. aureus internalization into bMEC by inhibiting NF-κB activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Effects of the presence of indium on the mammary gland ultrastructure, body weight, food intake and plasmatic prolactin concentration.

    Science.gov (United States)

    Ayadi, Ahlem; Maghraoui, Samira; Kammoun, Sayda; Tekaya, Leila

    2014-10-01

    Several studies have demonstrated the toxic effect of indium. This element induces impairments in many organs such as spleen, lungs and testicles after its systemic administration. Teratogenic and embryotoxic effects of this element have also been established. In the present study, we attempt to investigate the histological and the ultrastructural consequences of the presence of this element in mammary gland tissue using conventional transmission electron microscopy and to evaluate the incidences of its presence on the food intake, body weight and prolactin plasmatic concentration of lactating female rats. Our study showed that this element induced a significant decrease in food intake and body weight, and caused some cellular damage in the glandular epithelial cell such as cytoplasmic vacuolization and expansion of the ergastoplasm. The ultrastructural observations also showed many electron-dense surcharges in the lysosomes of the glandular epithelial cells. The electron probe microanalysis showed that these deposits are composed of indium and phosphorus. The lysosomes, known for their protective role of sequestrating foreign elements to avoid their diffusion in the blood, failed to stop the toxic effect of indium. © The Author 2014. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland.

    Science.gov (United States)

    Annunziato, Stefano; Kas, Sjors M; Nethe, Micha; Yücel, Hatice; Del Bravo, Jessica; Pritchard, Colin; Bin Ali, Rahmen; van Gerwen, Bas; Siteur, Bjørn; Drenth, Anne Paulien; Schut, Eva; van de Ven, Marieke; Boelens, Mirjam C; Klarenbeek, Sjoerd; Huijbers, Ivo J; van Miltenburg, Martine H; Jonkers, Jos

    2016-06-15

    Large-scale sequencing studies are rapidly identifying putative oncogenic mutations in human tumors. However, discrimination between passenger and driver events in tumorigenesis remains challenging and requires in vivo validation studies in reliable animal models of human cancer. In this study, we describe a novel strategy for in vivo validation of candidate tumor suppressors implicated in invasive lobular breast carcinoma (ILC), which is hallmarked by loss of the cell-cell adhesion molecule E-cadherin. We describe an approach to model ILC by intraductal injection of lentiviral vectors encoding Cre recombinase, the CRISPR/Cas9 system, or both in female mice carrying conditional alleles of the Cdh1 gene, encoding for E-cadherin. Using this approach, we were able to target ILC-initiating cells and induce specific gene disruption of Pten by CRISPR/Cas9-mediated somatic gene editing. Whereas intraductal injection of Cas9-encoding lentiviruses induced Cas9-specific immune responses and development of tumors that did not resemble ILC, lentiviral delivery of a Pten targeting single-guide RNA (sgRNA) in mice with mammary gland-specific loss of E-cadherin and expression of Cas9 efficiently induced ILC development. This versatile platform can be used for rapid in vivo testing of putative tumor suppressor genes implicated in ILC, providing new opportunities for modeling invasive lobular breast carcinoma in mice. © 2016 Annunziato et al.; Published by Cold Spring Harbor Laboratory Press.

  10. Molecular cloning, expression and purification of lactoferrin from Tibetan sheep mammary gland using a yeast expression system.

    Science.gov (United States)

    Li, Jianbo; Zhu, Wuzheng; Luo, Meirong; Ren, Honghui; Tang, Lu; Liao, Honghai; Wang, Yong

    2015-05-01

    This paper reports the successful expression of a lactoferrin gene-obtained from the mammary gland tissue of Tibetan sheep-in the yeast Pichia pastoris GS115 using pPICZαA as the recombinant plasmid and α-factor signal sequence for secretion. The recombinant lactoferrin was purified by ammonium sulfate precipitation, ion-exchange column chromatography and gel-filtration chromatography, and it had a molecular mass of 76kDa. We obtained an expression yield of >60mgL(-1) and specific activity of 2533.33Umg(-1). The antimicrobial activities and iron-binding behaviors of recombinant lactoferrin indicated that it was correctly folded and functional. Additionally, recombinant lactoferrin inhibited the growth of Escherichia coli JM109 and Staphylococcus aureus. These findings indicate that recombinant lactoferrin is a potential antibiotic for use on humans. This study also demonstrates the successful expression of recombinant lactoferrin using the eukaryotic host organism P. pastoris, paving the way for protein engineering using this gene. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. In vitro characterization and endocrine regulation of cholesterol and phospholipid transport in the mammary gland.

    Science.gov (United States)

    Ontsouka, Corneille Edgar; Huang, Xiao; Aliyev, Eldar; Albrecht, Christiane

    2017-01-05

    Cell-based studies previously showed that the ATP-binding cassette transporter A1 (ABCA1) transfers cholesterol across mammary epithelial cells (MEC). Data for phospholipid transport are lacking, and it is unclear from which cellular source the transported cholesterol stems, whether this transport activates signaling pathways, and how lactogenic hormones regulate it. To clarify these aspects, lipid transport and expressional analyses were performed in bovine primary (bMEC) and/or immortalized (MAC-T) MEC cultures. Lipid efflux and ABCA1, ABCG1 and liver X receptorα mRNA levels were higher in MAC-T than bMEC. In MAC-T, the transported cholesterol originated mainly from the plasma membrane. ABCA1 dependent cholesterol efflux was higher than phosphatidylcholine efflux, was suppressed by probucol (ABCA1 inhibitor), AG490 (janus kinase-2 inhibitor), PD98059 (mitogen activated protein kinase kinase inhibitor) and pretreatment with β-cyclodextrin (lowering membrane cholesterol). Insulin was the only hormone significantly increasing cholesterol efflux. In conclusion, this study gives novel mechanistic and regulatory insights into the transport of cholesterol and phospholipids in MEC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Immunocytochemical identification of myoepithelial cells in normal and neoplastic rat mammary glands with the lectins Griffonia simplicifolia-1 and pokeweed mitogen.

    Science.gov (United States)

    Hughes, C M; Rudland, P S

    1990-11-01

    Peroxidase-conjugated Griffonia simplicifolia-1 (GS-1) and pokeweed mitogen (PWM) histochemically stain only the myoepithelial cells and not the epithelial or fibroblastic cells of rat mammary glands preserved in methacarn or glutaraldehyde and embedded in paraffin. This pattern of staining occurs in other rat exocrine glands except the pancreas, but is the reverse of that seen in most lining epithelium. The histochemical binding of GS-1 and PWM to myoepithelial cells is inhibited specifically by D-galactose and by polymers of N-acetylglucosamine, respectively. GS-1 and its subcomponent, GS-1-B4, also bind to extracellular structures similar to those stained by anti-laminin serum. At the ultrastructural level, both conjugated GS-1 and PWM bind to the plasma membrane of the myoepithelial cells, as well as to the adjacent basement membrane. Non-metastasizing rat mammary tumors produced by dimethylbenz[a]anthracene, by derivative epithelial stem-cell lines, and by a transplantable tumor all contain more elongated myoepithelium-like cells as well as cuboidal epithelium-like cells; both cell types are neoplastic. The more elongated myoepithelium-like cells are stained by GS-1 and PWM, whereas the cuboidal epithelium-like cells are unstained. Moderately and strongly metastatic rat mammary tumors produced by epithelial cell lines and by transplantable tumors, respectively, contain no such neoplastic cells that bind either lectin. We suggest that the carbohydrate receptors for GS-1 and PWM are consistent markers for the presence of the myoepithelial cell in normal and tumorous rat mammary glands.

  13. ZnT4 (SLC30A4)-null ("lethal milk") mice have defects in mammary gland secretion and hallmarks of precocious involution during lactation.

    Science.gov (United States)

    McCormick, Nicholas H; Lee, Sooyeon; Hennigar, Stephen R; Kelleher, Shannon L

    2016-01-01

    During lactation, highly specialized secretory mammary epithelial cells (MECs) produce and secrete huge quantities of nutrients and nonnutritive factors into breast milk. The zinc (Zn) transporter ZnT4 (SLC30A4) transports Zn into the trans-Golgi apparatus for lactose synthesis, and across the apical cell membrane for efflux from MECs into milk. This is consistent with observations in "lethal milk" (lm/lm) mice, which have a truncation mutation in SLC30A4, and present with not only low milk Zn concentration, but also smaller mammary glands, decreased milk volume, and lactation failure by lactation day 2. However, the molecular underpinnings of these defects are not understood. Here, we used lactating C57BL/6J(lm/lm) (ZnT4-null) mice to explore the consequences of a ZnT4-null phenotype on mammary gland function during early lactation. Lactating C57BL/6J(lm/lm) mice had significantly fewer, smaller, and collapsed alveoli comprising swollen, lipid-filled MECs during early lactation. These defects were associated with decreased Akt expression and STAT5 activation, indicative of defects in MEC secretion. In addition, increased expression of ZnT2, TNF-α, and cleaved e-cadherin concomitant with increased activation of STAT3 implicated the loss of ZnT4 in precocious activation of involution. Collectively, our study indicates that the loss of ZnT4 has profound consequences on MEC secretion and may promote tissue remodeling in the mammary gland during early lactation. Copyright © 2016 the American Physiological Society.

  14. Single Nucleotide Polymorphism Discovery in Bovine Pituitary Gland Using RNA-Seq Technology.

    Directory of Open Access Journals (Sweden)

    Chandra Shekhar Pareek

    Full Text Available Examination of bovine pituitary gland transcriptome by strand-specific RNA-seq allows detection of putative single nucleotide polymorphisms (SNPs within potential candidate genes (CGs or QTLs regions as well as to understand the genomics variations that contribute to economic trait. Here we report a breed-specific model to successfully perform the detection of SNPs in the pituitary gland of young growing bulls representing Polish Holstein-Friesian (HF, Polish Red, and Hereford breeds at three developmental ages viz., six months, nine months, and twelve months. A total of 18 bovine pituitary gland polyA transcriptome libraries were prepared and sequenced using the Illumina NextSeq 500 platform. Sequenced FastQ databases of all 18 young bulls were submitted to NCBI-SRA database with NCBI-SRA accession numbers SRS1296732. For the investigated young bulls, a total of 113,882,3098 raw paired-end reads with a length of 156 bases were obtained, resulting in an approximately 63 million paired-end reads per library. Breed-wise, a total of 515.38, 215.39, and 408.04 million paired-end reads were obtained for Polish HF, Polish Red, and Hereford breeds, respectively. Burrows-Wheeler Aligner (BWA read alignments showed 93.04%, 94.39%, and 83.46% of the mapped sequencing reads were properly paired to the Polish HF, Polish Red, and Hereford breeds, respectively. Constructed breed-specific SNP-db of three cattle breeds yielded at 13,775,885 SNPs. On an average 765,326 breed-specific SNPs per young bull were identified. Using two stringent filtering parameters, i.e., a minimum 10 SNP reads per base with an accuracy ≥ 90% and a minimum 10 SNP reads per base with an accuracy = 100%, SNP-db records were trimmed to construct a highly reliable SNP-db. This resulted in a reduction of 95,7% and 96,4% cut-off mark of constructed raw SNP-db. Finally, SNP discoveries using RNA-Seq data were validated by KASP™ SNP genotyping assay. The comprehensive QTLs/CGs analysis

  15. Single Nucleotide Polymorphism Discovery in Bovine Pituitary Gland Using RNA-Seq Technology

    Science.gov (United States)

    Pareek, Chandra Shekhar; Smoczyński, Rafał; Kadarmideen, Haja N.; Dziuba, Piotr; Błaszczyk, Paweł; Sikora, Marcin; Walendzik, Paulina; Grzybowski, Tomasz; Pierzchała, Mariusz; Horbańczuk, Jarosław; Szostak, Agnieszka; Ogluszka, Magdalena; Zwierzchowski, Lech; Czarnik, Urszula; Fraser, Leyland; Sobiech, Przemysław; Wąsowicz, Krzysztof; Gelfand, Brian; Feng, Yaping; Kumar, Dibyendu

    2016-01-01

    Examination of bovine pituitary gland transcriptome by strand-specific RNA-seq allows detection of putative single nucleotide polymorphisms (SNPs) within potential candidate genes (CGs) or QTLs regions as well as to understand the genomics variations that contribute to economic trait. Here we report a breed-specific model to successfully perform the detection of SNPs in the pituitary gland of young growing bulls representing Polish Holstein-Friesian (HF), Polish Red, and Hereford breeds at three developmental ages viz., six months, nine months, and twelve months. A total of 18 bovine pituitary gland polyA transcriptome libraries were prepared and sequenced using the Illumina NextSeq 500 platform. Sequenced FastQ databases of all 18 young bulls were submitted to NCBI-SRA database with NCBI-SRA accession numbers SRS1296732. For the investigated young bulls, a total of 113,882,3098 raw paired-end reads with a length of 156 bases were obtained, resulting in an approximately 63 million paired-end reads per library. Breed-wise, a total of 515.38, 215.39, and 408.04 million paired-end reads were obtained for Polish HF, Polish Red, and Hereford breeds, respectively. Burrows-Wheeler Aligner (BWA) read alignments showed 93.04%, 94.39%, and 83.46% of the mapped sequencing reads were properly paired to the Polish HF, Polish Red, and Hereford breeds, respectively. Constructed breed-specific SNP-db of three cattle breeds yielded at 13,775,885 SNPs. On an average 765,326 breed-specific SNPs per young bull were identified. Using two stringent filtering parameters, i.e., a minimum 10 SNP reads per base with an accuracy ≥ 90% and a minimum 10 SNP reads per base with an accuracy = 100%, SNP-db records were trimmed to construct a highly reliable SNP-db. This resulted in a reduction of 95,7% and 96,4% cut-off mark of constructed raw SNP-db. Finally, SNP discoveries using RNA-Seq data were validated by KASP™ SNP genotyping assay. The comprehensive QTLs/CGs analysis of 76 QTLs

  16. [Physical examination and palpation findings of mammary glands and indications of udder health in goat milk].

    Science.gov (United States)

    Schulz, J; Fahr, R D; Finn, G; Naumann, I

    1999-04-01

    In dairy goats there is less evidence for relationships between udder form traits, results of physical udder examinations and mastitis indicators in the milk than in dairy cows. In 413 goats (predominantly Weisse Deutsche Edelziege and Bunte Deutsche Edelziege) from five herds (free from C.A.E.) repeated investigations of 2537 udder halves and fore milk samples were carried out in order to compare udder traits with findings in the milk. Less than 20% positive bacteriological findings and a low incidence of clinical mastitis testified a good clinical udder health status of the herds. Small teat-floor distances, loose hanging of the udders and bottle-shaped teats, findings which tended to become more frequent as lactation and lactation numbers progressed, indurative alterations of the mammary tissues and the teats tended to be connected with higher milk cell counts (> 1 million/microliter), more polymorphonuclear milk cells (> 40%), higher electrical milk conductivity (> 6.8 mS/cm) and lower milk lactose content (bad state of foot trimming. It is proposed to include the studied udder traits into herd health programs and breeding schemes for goats.

  17. MicroRNAs in the development and neoplasia of the mammary gland [version 2; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Jena

    2017-10-01

    Full Text Available Study on the role of microRNAs (miRs as regulators of gene expression through posttranscriptional gene silencing is currently gaining much interest,due to their wide involvement in different physiological processes. Understanding mammary gland development, lactation, and neoplasia in relation to miRs is essential. miR expression profiling of the mammary gland from different species in various developmental stages shows their role as critical regulators of development. miRs such as miR-126, miR-150, and miR-145 have been shown to be involved in lipid metabolism during lactation. In addition, lactogenic hormones influence miR expression as evidenced by overexpression of miR-148a in cow mammary epithelial cells, leading to enhanced lactation. Similarly, the miR-29 family modulates lactation-related gene expression by regulating DNA methylation of their promoters. Besides their role in development, lactation and involution, miRs are responsible for breast cancer development. Perturbed estrogen (E2 signaling is one of the major causes of breast cancer. Increased E2 levels cause altered expression of ERα, and ERα-miR cross-talk promotes tumour progression. miRs, such as miR-206, miR-34a, miR-17-5p, and miR-125 a/b are found to be tumour suppressors; whereas miR-21, miR-10B, and miR-155 are oncogenes. Oncogenic miRs like miR-21, miR-221, and miR-210 are overexpressed in triple negative breast cancer cases which can be diagnostic biomarker for this subtype of cancer.  This review focuses on the recent findings concerning the role of miRs in developmental stages of the mammary gland (mainly lactation and involution stages and their involvement in breast cancer progression. Further studies in this area will help us to understand the molecular details of mammary gland biology, as well as miRs that could be therapeutic targets of breast cancer.

  18. MicroRNAs in the development and neoplasia of the mammary gland [version 1; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Jena

    2017-06-01

    Full Text Available Study on the role of microRNAs (miRs as regulators of gene expression through posttranscriptional gene silencing is currently gaining much interest,due to their wide involvement in different physiological processes. Understanding mammary gland development, lactation, and neoplasia in relation to miRs is essential. miR expression profiling of the mammary gland from different species in various developmental stages shows their role as critical regulators of development. miRs such as miR-126, miR-150, and miR-145 have been shown to be involved in lipid metabolism during lactation. In addition, lactogenic hormones influence miR expression as evidenced by overexpression of miR-148a in cow mammary epithelial cells, leading to enhanced lactation. Similarly, the miR-29 family modulates lactation-related gene expression by regulating DNA methylation of their promoters. Besides their role in development, lactation and involution, miRs are responsible for breast cancer development. Perturbed estrogen (E2 signaling is one of the major causes of breast cancer. Increased E2 levels cause altered expression of ERα, and ERα-miR cross-talk promotes tumour progression. miRs, such as miR-206, miR-34a, miR-17-5p, and miR-125 a/b are found to be tumour suppressors; whereas miR-21, miR-10B, and miR-155 are oncogenes.Studies using an ACI rat model showed similar findings of miR dysregulation due to excess E2, and a natural phenol antioxidant ellagic acid showed therapeutic properties by reversing the miR dysregulation. This review focuses on the recent findings concerning the role of miRs in developmental stages of the mammary gland (mainly lactation and involution stages and their involvement in breast cancer progression. Further studies in this area will help us understand the molecular details of mammary gland biology,as well as miRs that could be therapeutic targets of breast cancer.

  19. Comparative value of clinical, cytological, and histopathological features in feline mammary gland tumors; an experimental model for the study of human breast cancer.

    Science.gov (United States)

    Shafiee, Radmehr; Javanbakht, Javad; Atyabi, Nahid; Bahrami, Alimohammad; Kheradmand, Danial; Safaei, Reyhaneh; Khadivar, Farshid; Hosseini, Ehsan

    2013-08-13

    regions, local invasiveness and enlarged nuclei were observed. The samples included 3 tumors of mammary glands mammary tumors were complex carcinomas (n = 2) and adenocarcinoma (n = 1). The histological grades of the 3 cases were as follows: grade II, (1/3); grade III, (2/3) with high mitotic index. The preferential localization of mammary neoplasms was in the inguinal lobe (1/3 case) and abdominal lobes (2/3 cases). Furthermore, 1case of the inguinal mass affected the left caudo-inguinal lobe and 2cases right cranio and caudo abdominal lobes. The study concluded that cytology could be used as a quick, rapid, field diagnostic technique in combination with histopathology for the diagnosis of feline mammary tumors (FMTs). Our findings in feline MTs indicate that FMTs could be useful as an animal model of human breast cancer. Moreover, because of the similarity of the cytohistopathological findings in the human and feline mammary gland tumours, it is possible to use the same cytopathological criteria applied in human pathology for the diagnosis of feline mammary gland tumours. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2047361423103295.

  20. A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells.

    Science.gov (United States)

    Butt, Alison J; Roberts, Caroline G; Seawright, Alan A; Oelrichs, Peter B; Macleod, John K; Liaw, Tracy Y E; Kavallaris, Maria; Somers-Edgar, Tiffany J; Lehrbach, Gillian M; Watts, Colin K; Sutherland, Robert L

    2006-09-01

    Phytochemicals have provided an abundant and effective source of therapeutics for the treatment of cancer. Here we describe the characterization of a novel plant toxin, persin, with in vivo activity in the mammary gland and a p53-, estrogen receptor-, and Bcl-2-independent mode of action. Persin was previously identified from avocado leaves as the toxic principle responsible for mammary gland-specific necrosis and apoptosis in lactating livestock. Here we used a lactating mouse model to confirm that persin has a similar cytotoxicity for the lactating mammary epithelium. Further in vitro studies in a panel of human breast cancer cell lines show that persin selectively induces a G2-M cell cycle arrest and caspase-dependent apoptosis in sensitive cells. The latter is dependent on expression of the BH3-only protein Bim. Bim is a sensor of cytoskeletal integrity, and there is evidence that persin acts as a microtubule-stabilizing agent. Due to the unique structure of the compound, persin could represent a novel class of microtubule-targeting agent with potential specificity for breast cancers.

  1. SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma.

    Science.gov (United States)

    Hsieh, Min-Shu; Lee, Yi-Hsuan; Chang, Yih-Leong

    2016-10-01

    Transcription factor SRY-related HMG-box 10 (SOX10) is an important marker for melanocytic, schwannian, myoepithelial, and some salivary gland tumors. The aim of this study was to investigate SOX10 expression more thoroughly in the salivary gland neoplasms, including mammary analogue secretory carcinoma and hyalinizing clear cell carcinoma harboring specific genetic rearrangements. A new rabbit monoclonal anti-SOX10 antibody (clone EP268) was used to examine SOX10 expression in 14 different types of salivary gland tumors. We found that acinic cell carcinoma (AciCC), adenoid cystic carcinoma, mammary analogue secretory carcinoma (MASC), epithelial-myoepithelial carcinoma, low-grade salivary duct carcinoma, sialoblastoma, basal cell adenocarcinoma, basal cell adenoma, and pleomorphic adenoma were SOX10 positive. Salivary duct carcinoma, lymphoepithelial carcinoma, hyalinizing clear cell carcinoma, and oncocytoma were SOX10 negative. Earlier, mucoepidermoid carcinoma (MEC) was considered a SOX10-negative tumor. This study identified a subgroup of SOX10-positive MEC cases with characteristic polygonal epithelial cells, pale-to-eosinophilic cytoplasm, and colloid-like dense eosinophilic material. Our data show SOX10 expression can be observed in salivary gland tumors with either one of the 4 cell types: acinic cells, cuboidal ductal cells with low-grade cytologic features, basaloid cells, and myoepithelial cells. In this article we thoroughly evaluated SOX10 expression in salivary gland tumors. SOX10 is useful in the differential diagnosis between myoepithelial carcinoma with clear cell features and hyalinizing clear cell carcinoma. It can also be used to discriminate low-grade salivary duct carcinoma from high-grade ones. Pathologists should be cautious with the interpretation of SOX10 positivity in salivary gland tumors, and correlation with histologic feature is mandatory. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Stromal–epithelial cell interactions and alteration of branching morphogenesis in macromastic mammary glands

    Science.gov (United States)

    Zhong, Aimei; Wang, Guohua; Yang, Jie; Xu, Qijun; Yuan, Quan; Yang, Yanqing; Xia, Yun; Guo, Ke; Horch, Raymund E; Sun, Jiaming

    2014-01-01

    True macromastia is a rare but disabling condition characterized by massive breast growth. The aetiology and pathogenic mechanisms for this disorder remain largely unexplored because of the lack of in vivo or in vitro models. Previous studies suggested that regulation of epithelial cell growth and development by oestrogen was dependent on paracrine growth factors from the stroma. In this study, a co-culture model containing epithelial and stromal cells was used to investigate the interactions of these cells in macromastia. Epithelial cell proliferation and branching morphogenesis were measured to assess the effect of macromastic stromal cells on epithelial cells. We analysed the cytokines secreted by stromal cells and identified molecules that were critical for effects on epithelial cells. Our results indicated a significant increase in cell proliferation and branching morphogenesis of macromastic and non-macromastic epithelial cells when co-cultured with macromastic stromal cells or in conditioned medium from macromastic stromal cells. Hepatocyte growth factor (HGF) is a key factor in epithelial–stromal interactions of macromastia-derived cell cultures. Blockade of HGF with neutralizing antibodies dramatically attenuated epithelial cell proliferation in conditioned medium from macromastic stromal cells. The epithelial–stromal cell co-culture model demonstrated reliability for studying interactions of mammary stromal and epithelial cells in macromastia. In this model, HGF secreted by macromastic stromal cells was found to play an important role in modifying the behaviour of co-cultured epithelial cells. This model allows further studies to investigate basic cellular and molecular mechanisms in tissue from patients with true breast hypertrophy. PMID:24720804

  3. In Vitro Validation of the Hippo Pathway as a Pharmacological Target for Canine Mammary Gland Tumors.

    Science.gov (United States)

    Guillemette, Samantha; Rico, Charlène; Godin, Philippe; Boerboom, Derek; Paquet, Marilène

    2017-08-18

    Canine mammary tumors (CMTs) are the most common neoplasms in intact female dogs. Some clinical and molecular similarities between certain CMT subtypes and breast cancer make them a potential model for the study of the human disease. As misregulated Hippo signaling is thought to play an important role in breast cancer development and also occurs in CMTs, we sought to determine if Hippo represents a valid pharmacological target for the treatment of CMTs. Six CMT cell lines were assessed for their expression of the Hippo pathway effectors YAP and TAZ and for their sensitivity to verteporfin, an inhibitor of YAP-mediated transcriptional coactivation. Four cell lines that expressed YAP (CMT-9, -12, -28, -47) were found to be very sensitive to verteporfin treatment, which killed the cells through induction of apoptosis with ED50 values of 14-79 nM. Conversely, two YAP-negative cell lines (CF-35, CMT-25) were an order of magnitude more resistant to verteporfin. Verteporfin suppressed the expression of YAP/TAZ target genes, particularly CYR61 and CTGF, which play important roles in breast cancer development. Verteporfin was also able to inhibit cell migration and anchorage-independent growth. Likewise, verteporfin efficiently suppressed tumor cell invasiveness in the CMT-28 and -47 lines, but not in CF-35 cells. Together, our findings provide proof of principle that pharmacological targeting of the Hippo pathway compromises the viability and attenuates the malignant behavior of CMT cells. These results will serve as the basis for the development of novel chemotherapeutic approaches for CMTs that could translate to human medicine.

  4. Cytogenetic and immunohistochemical characterization of mammary analogue secretory carcinoma of salivary glands.

    Science.gov (United States)

    Khurram, Syed A; Sultan-Khan, Jemel; Atkey, Neil; Speight, Paul M

    2016-12-01

    Mammary analogue secretory carcinoma (MASC), initially considered a subset of acinic cell carcinoma (ACC), harbors an ETV6 translocation [t(12:15)(p13:25 q)] and is now regarded as a distinct entity. Several putative markers to differentiate MASC from ACC have been reported; however, the immunohistochemical profile is still being explored and updated. The purpose of this study was to further explore the cytogenetic and immunohistochemical profile of MASC. Cases were analyzed for ETV6 translocation using fluorescent in situ hybridization and stained for CK8, amylase, mammaglobin, GCDFP-15, MUC1, MUC4, STAT5a, Ki-67 (n = 37), CK7, Cam5.2, CK14, SMA, p63, S100, vimentin and DOG1 (n = 42). Histochemical stains for mucins were also performed and data collected for age, sex, and site. Fluorescent in situ hybridization showed 9 cases with ETV6 rearrangement and 2 with increased ETV6 copies. These 11 cases showed an absence of PAS-D-resistant granules, with 10 of 11 showing strong S100, mammaglobin, and STAT5a staining. All ACCs showed diffuse DOG1 staining, whereas 8/11 MASCs were negative and 3 showed only focal DOG1 staining. DOG1 can be used in conjunction with PAS-D, S100, and mammaglobin to identify MASCs. Cases with increased ETV6 copies are a novel finding with a similar immunostaining profile and should be considered as MASCs. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Kisspeptin-10 Induces β-Casein Synthesis via GPR54 and Its Downstream Signaling Pathways in Bovine Mammary Epithelial Cells.

    Science.gov (United States)

    Sun, Jianhua; Liu, Juxiong; Huang, Bingxu; Kan, Xingchi; Chen, Guangxin; Wang, Wei; Fu, Shoupeng

    2017-12-05

    Kisspeptins (Kps) play a key role in the regulation of GnRH axis and as an anti-metastasis agent by binding with GPR54. Recently, we observed that the expression of GPR54 was higher in the lactating mammary tissues of dairy cows with high-quality milk (0.81 ± 0.13 kg/day of milk protein yield; 1.07 ± 0.18 kg/day of milk fat yield) than in those with low-quality milk (0.51 ± 0.14 kg/day of milk protein yield; 0.67 ± 0.22 kg/day of milk fat yield). We hypothesized that Kp-10 might regulate the milk protein, β-casein (CSN2) synthesis via GPR54 and its downstream signaling. First, we isolated the bovine mammary epithelial cells (bMECs) from lactating Holstein dairy cows, and treated them with different concentrations of Kp-10. Compared with the control cells, the synthesis of CSN2 is significantly increased at a concentration of 100 nM of Kp-10. In addition, the increased effect of CSN2 synthesis was blocked when the cells were pre-treated with the selective inhibitor of GPR54 Peptide-234 (P-234). Mechanistic study revealed that Kp-10 activated ERK1/2, AKT, mTOR and STAT5 in bMECs. Moreover, inhibiting ERK1/2, AKT, mTOR and STAT5 with U0126, MK2206, Rapamycin and AG490 could block the effects of Kp-10. Together, these results demonstrate that Kp-10 facilitates the synthesis of CSN2 via GPR54 and its downstream signaling pathways mTOR, ERK1/2, STAT5 and AKT.

  6. Kisspeptin-10 Induces β-Casein Synthesis via GPR54 and Its Downstream Signaling Pathways in Bovine Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Jianhua Sun

    2017-12-01

    Full Text Available Kisspeptins (Kps play a key role in the regulation of GnRH axis and as an anti-metastasis agent by binding with GPR54. Recently, we observed that the expression of GPR54 was higher in the lactating mammary tissues of dairy cows with high-quality milk (0.81 ± 0.13 kg/day of milk protein yield; 1.07 ± 0.18 kg/day of milk fat yield than in those with low-quality milk (0.51 ± 0.14 kg/day of milk protein yield; 0.67 ± 0.22 kg/day of milk fat yield. We hypothesized that Kp-10 might regulate the milk protein, β-casein (CSN2 synthesis via GPR54 and its downstream signaling. First, we isolated the bovine mammary epithelial cells (bMECs from lactating Holstein dairy cows, and treated them with different concentrations of Kp-10. Compared with the control cells, the synthesis of CSN2 is significantly increased at a concentration of 100 nM of Kp-10. In addition, the increased effect of CSN2 synthesis was blocked when the cells were pre-treated with the selective inhibitor of GPR54 Peptide-234 (P-234. Mechanistic study revealed that Kp-10 activated ERK1/2, AKT, mTOR and STAT5 in bMECs. Moreover, inhibiting ERK1/2, AKT, mTOR and STAT5 with U0126, MK2206, Rapamycin and AG490 could block the effects of Kp-10. Together, these results demonstrate that Kp-10 facilitates the synthesis of CSN2 via GPR54 and its downstream signaling pathways mTOR, ERK1/2, STAT5 and AKT.

  7. Bovine Mammary Nutrigenomics and Changes in the Milk Composition due to Rapeseed or Sunflower Oil Supplementation of High-Forage or High-Concentrate Diets.

    Science.gov (United States)

    Leroux, Christine; Bernard, Laurence; Faulconnier, Yannick; Rouel, Jacques; de la Foye, Anne; Domagalski, Jordann; Chilliard, Yves

    2016-01-01

    Fatty acid (FA) composition plays a crucial role in milk nutritional quality. Despite the known nutritional regulation of ruminant milk composition, the overall mammary mechanisms underlying this regulation are far from being understood. The aim of our study was to determine nutritional regulation of mammary transcriptomes in relation to the cow milk composition. Twelve cows received diets differing in the forage-to-concentrate ratio [high forage (HF) and low forage (LF)] supplemented or not with lipids [HF with whole intact rapeseeds (RS) and LF sunflower oil (SO)] in a 4 × 4 Latin square design. Milk production and FA composition were determined. The gene expression profile was studied using RT-qPCR and a bovine microarray. Our results showed a higher amplitude of milk composition and mammary transcriptome responses to lipid supplementation with the LF-SO compared with the LF diet than with the HF-RS compared with the HF diet. Forty-nine differentially expressed genes, including genes involved in lipid metabolism, were identified with LF-SO versus LF, whereas RS supplementation to the HF diet did not affect the mammary transcriptome. This study highlights different responses to lipid supplementation of milk production and composition and mammary transcriptomes depending on the nature of lipid supplementation and the percentage of dietary concentrate. © 2016 S. Karger AG, Basel.

  8. Pathologic findings of experimentally induced Streptococcus uberis infection in the mammary gland of cows.

    Science.gov (United States)

    Thomas, L H; Haider, W; Hill, A W; Cook, R S

    1994-12-01

    Twenty-five quarters of 12 dairy cows, 3 to 8 years old, with a bacteriologic history of freedom from infection with Streptococcus uberis were inoculated via the teat canal with S uberis (23 quarters) or sterile medium (2 quarters). The cows were sent to slaughter 1, 3, or 6 days later. Acute inflammatory response involving accumulation of large numbers of polymorphonuclear, neutrophilic leukocytes (neutrophils) in the secretory acini was recognized after 24 hours in infected cows. After 6 days, the neutrophil response was still evident, but infiltration of septa by lymphocytes, septal edema, extensive vacuolation of secretory cells, focal necrosis of alveoli, small outgrowths of the secretory and ductular epithelium, and widespread hypertrophy of the ductular epithelium also were recognized. Early stages of involution and fibrosis also were evident at that stage. Streptococci were identified by immunoperoxidase labeling, free or phagocytosed, in macrophages; in the alveolar lumina, adherent to damaged secretory or ductular epithelium; in the subepithelium and septal tissue; and in lymphatic vessels and lymph nodes. The importance of the macrophage as the primary phagocytic cell is highlighted, and doubt is cast on the value of the exuberant neutrophil response by the host in defense of the gland.

  9. Lysozyme Expression Can be Useful to Distinguish Mammary Analog Secretory Carcinoma from Acinic Cell Carcinoma of Salivary Glands.

    Science.gov (United States)

    Mariano, Fernanda Viviane; Gómez, Camila Andrea Concha; de Souza do Nascimento, Juliana; Dos Santos, Harim Tavares; Egal, Erika Said; Montalli, Victor Angelo Martins; Vargas, Pablo Agustin; de Almeida, Oslei Paes; Altemani, Albina

    2016-12-01

    Lysozyme is an enzymatic marker of acinar and intercalated duct cells of normal salivary glands. The aim of this study was to verify whether lysozyme expression could be useful to distinguish acinic cell carcinoma (ACC) from its main mimic, mammary analog secretory carcinoma (MASC). For comparison, DOG1 expression was analyzed as well. Seventeen cases of ACC, 15 MASC, and 125 other salivary tumors were studied. Lysozyme expression was found in tumor cells as well as in secreted material of MASC (86.6 % of cases) and in ductal cells of epithelial-myoepithelial carcinoma (EMC-53.8 %), pleomorphic adenoma (PA-29.1 %) and polymorphous low-grade adenocarcinoma (PLGA-23.8 %). However, in ACC, lysozyme was not expressed. Three patterns of DOG1 staining were seen: apical-luminal, cytoplasmic, and mixed cytoplasmic/membranous. The apical-luminal pattern was detected in ductal cells of ACC (58.8 % of cases), EMC (38.4 %), adenoid-cystic carcinoma (AdCC-35.3 %), PA (8.3 %), and PLGA (4.8 %). These tumors also showed mixed membranous/cytoplasmic staining for DOG1. MASC, mucoepidermoid, and salivary duct carcinomas exhibited only DOG1 cytoplasmic staining. In conclusion, lysozyme cannot be used as a marker of acinar differentiation in salivary tumors. However, lysozyme expression can be helpful to distinguish MASC from ACC due to its high frequency in the former and absence in ACC. It is likely that in MASC, lysozyme expression may reflect a lactational-like secretory differentiation since lysozyme belongs to breast milk proteins. Regarding DOG1 expression, the apical-luminal pattern is related to acinar and intercalated duct differentiation whereas the cytoplasmic staining does not seem to be associated with a specific cellular phenotype.

  10. Nocardia cyriacigeogica from Bovine Mastitis Induced In vitro Apoptosis of Bovine Mammary Epithelial Cells via Activation of Mitochondrial-Caspase Pathway

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    Wei Chen

    2017-05-01

    Full Text Available Nocardia is one of the causing agents of bovine mastitis and increasing prevalence of nocardial mastitis in shape of serious outbreaks has been reported from many countries. However, the mechanisms by which this pathogen damages the bovine mammary epithelial cells (bMECs is not yet studied. Therefore, this study was designed with the aim to evaluate the apoptotic effects elicited by Nocardia and to investigate the pathway by which the Nocardia induce apoptosis in bMECs. Clinical Nocardia cyriacigeorgica strain from bovine mastitis was used to infect the bMECs for different time intervals, viz. 1, 3, 6, 12, and 18 h, and then the induced effects on bMECs were studied using adhesion and invasion assays, release of lactate dehydrogenase (LDH, apoptosis analysis by annexin V and propidium iodide (PI double staining, morphological, and ultrastructural observations under scanning electron microscope (SEM and transmission electron microscope (TEM, mitochondrial transmembrane potential (ΔΨm assay using flow cytometry, and the protein quantification of mitochondrial cytochrome c and caspase-9 and caspase-3 by western blotting. The results of this study showed that N. cyriacigeorgica possessed the abilities of adhesion and invasion to bMECs. N. cyriacigeorgica was found to collapse mitochondrial transmembrane potential, significantly (p < 0.05 release mitochondrial cytochrome c and ultimately induce cell apoptosis. Additionally, it promoted casepase-9 (p < 0.01 and casepase-3 (p < 0.05 levels, significantly (p < 0.01 increased the release of LDH and promoted DNA fragmentation which further confirmed the apoptosis. Furthermore, N. cyriacigeorgica induced apoptosis/necrosis manifested specific ultrastructure features under TEM, such as swollen endoplasmic reticulum, cristae degeneration, and swelling of mitochondria, vesicle formation on the cell surface, rupturing of cell membrane and nuclear membrane, clumping, fragmentation, and margination of

  11. Nocardia cyriacigeogica from Bovine Mastitis Induced In vitro Apoptosis of Bovine Mammary Epithelial Cells via Activation of Mitochondrial-Caspase Pathway

    Science.gov (United States)

    Chen, Wei; Liu, Yongxia; Zhang, Limei; Gu, Xiaolong; Liu, Gang; Shahid, Muhammad; Gao, Jian; Ali, Tariq; Han, Bo

    2017-01-01

    Nocardia is one of the causing agents of bovine mastitis and increasing prevalence of nocardial mastitis in shape of serious outbreaks has been reported from many countries. However, the mechanisms by which this pathogen damages the bovine mammary epithelial cells (bMECs) is not yet studied. Therefore, this study was designed with the aim to evaluate the apoptotic effects elicited by Nocardia and to investigate the pathway by which the Nocardia induce apoptosis in bMECs. Clinical Nocardia cyriacigeorgica strain from bovine mastitis was used to infect the bMECs for different time intervals, viz. 1, 3, 6, 12, and 18 h, and then the induced effects on bMECs were studied using adhesion and invasion assays, release of lactate dehydrogenase (LDH), apoptosis analysis by annexin V and propidium iodide (PI) double staining, morphological, and ultrastructural observations under scanning electron microscope (SEM) and transmission electron microscope (TEM), mitochondrial transmembrane potential (ΔΨm) assay using flow cytometry, and the protein quantification of mitochondrial cytochrome c and caspase-9 and caspase-3 by western blotting. The results of this study showed that N. cyriacigeorgica possessed the abilities of adhesion and invasion to bMECs. N. cyriacigeorgica was found to collapse mitochondrial transmembrane potential, significantly (p < 0.05) release mitochondrial cytochrome c and ultimately induce cell apoptosis. Additionally, it promoted casepase-9 (p < 0.01) and casepase-3 (p < 0.05) levels, significantly (p < 0.01) increased the release of LDH and promoted DNA fragmentation which further confirmed the apoptosis. Furthermore, N. cyriacigeorgica induced apoptosis/necrosis manifested specific ultrastructure features under TEM, such as swollen endoplasmic reticulum, cristae degeneration, and swelling of mitochondria, vesicle formation on the cell surface, rupturing of cell membrane and nuclear membrane, clumping, fragmentation, and margination of chromatin. The

  12. Exposure to Ionizing Radiation Causes Long-Term Increase in Serum Estradiol and Activation of PI3K-Akt Signaling Pathway in Mouse Mammary Gland

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    Suman, Shubhankar [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC (United States); Johnson, Michael D. [Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC (United States); Fornace, Albert J. [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC (United States); Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC (United States); Datta, Kamal, E-mail: kd257@georgetown.edu [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC (United States)

    2012-10-01

    Purpose: Exposure to ionizing radiation is an established risk factor for breast cancer. Radiation exposure during infancy, childhood, and adolescence confers the highest risk. Although radiation is a proven mammary carcinogen, it remains unclear where it acts in the complex multistage process of breast cancer development. In this study, we investigated the long-term pathophysiologic effects of ionizing radiation at a dose (2 Gy) relevant to fractionated radiotherapy. Methods and Materials: Adolescent (6-8 weeks old; n = 10) female C57BL/6J mice were exposed to 2 Gy total body {gamma}-radiation, the mammary glands were surgically removed, and serum and urine samples were collected 2 and 12 months after exposure. Molecular pathways involving estrogen receptor-{alpha} (ER{alpha}) and phosphatidylinositol-3-OH kinase (PI3K)-Akt signaling were investigated by immunohistochemistry and Western blot. Results: Serum estrogen and urinary levels of the oncogenic estrogen metabolite (16{alpha}OHE1) were significantly increased in irradiated animals. Immunostaining for the cellular proliferative marker Ki-67 and cyclin-D1 showed increased nuclear accumulation in sections of mammary glands from irradiated vs. control mice. Marked increase in p85{alpha}, a regulatory sub-unit of the PI3K was associated with increase in Akt, phospho-Akt, phospho-BAD, phospho-mTOR, and c-Myc in irradiated samples. Persistent increase in nuclear ER{alpha} in mammary tissues 2 and 12 months after radiation exposure was also observed. Conclusions: Taken together, our data not only support epidemiologic observations associating radiation and breast cancer but also, specify molecular events that could be involved in radiation-induced breast cancer.

  13. Loss of EZH2 results in precocious mammary gland development and activation of STAT5-dependent genes

    Science.gov (United States)

    Yoo, Kyung Hyun; Oh, Sumin; Kang, Keunsoo; Hensel, Tim; Robinson, Gertraud W.; Hennighausen, Lothar

    2015-01-01

    Establishment and differentiation of mammary alveoli during pregnancy are controlled by prolactin through the transcription factors STAT5A and STAT5B (STAT5), which also regulate temporal activation of mammary signature genes. This study addressed the question whether the methyltransferase and transcriptional co-activator EZH2 controls the differentiation clock of mammary epithelium. Ablation of Ezh2 from mammary stem cells resulted in precocious differentiation of alveolar epithelium during pregnancy and the activation of mammary-specific STAT5 target genes. This coincided with enhanced occupancy o