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Sample records for accelerates mammary tumorprogression

  1. Activated type I TGFbeta receptor (Alk5) kinase confers enhancedsurvival to mammary epithelial cells and accelerates mammary tumorprogression

    Muraoka-Cook, Rebecca S.; Shin, Incheol; Yi, Jae Youn; Easterly,Evangeline; Barcellos-Hoff, Mary Helen; Yingling, Jonathan M.; Zent, Roy; Arteaga, Carlos L.

    2005-01-02

    The transforming growth factor-betas (TGF{beta}s) are members of a large superfamily of pleiotropic cytokines that also includes the activins and the bone morphogenetic proteins (BMPs). Members of the TGF{beta} family regulate complex physiological processes such cell proliferation, differentiation, adhesion, cell-cell and cell-matrix interactions, motility, and cell death, among others (Massague, 1998). Dysregulation of TGF{beta} signaling contributes to several pathological processes including cancer, fibrosis, and auto-immune disorders (Massague et al., 2000). The TGF{beta}s elicit their biological effects by binding to type II and type I transmembrane receptor serine-threonine kinases (T{beta}RII and T{beta}RI) which, in turn, phosphorylated Smad 2 and Smad 3. Phosphorylated Smad 2/3 associate with Smad 4 and, as a heteromeric complex, translocate to the nucleus where they regulate gene transcription. The inhibitory Smad7 down regulates TGF{beta} signaling by binding to activated T{beta}RI and interfering with its ability to phosphorylate Smad 2/3 (Derynck and Zhang, 2003; Shi and Massague, 2003). Signaling is also regulated by Smad proteolysis. TGF{beta} receptor-mediated activation results in multi-ubiquitination of Smad 2 in the nucleus and subsequent degradation of Smad 2 by the proteasome (Lo and Massague, 1999). Activation of TGF{beta} receptors also induces mobilization of a Smad 7-Smurf complex from the nucleus to the cytoplasm; this complex recognizes the activated receptors and mediates their ubiquitination and internalization via caveolin-rich vesicles, leading to termination of TGF{beta} signaling (Di Guglielmo et al., 2003). Other signal transducers/pathways have been implicated in TGF{beta} actions. These include the extracellular signal-regulated kinase (Erk), c-Jun N-terminal kinase (Jnk), p38 mitogen-activated protein kinase (MAPK), protein phosphatase PP2A, phosphatidylinositol-3 kinase (PI3K), and the family of Rho GTPases [reviewed in (Derynck and Zhang, 2003)]. Although signaling by Smads has been shown to be causally associated with the anti-proliferative effect of TGF{beta} (Datto et al., 1999; Liu et al., 1997), the role of non-Smad effectors on mediating the cellular effects of TGF{beta} is less well characterized.

  2. Accelerated apoptosis in the Timp-3–deficient mammary gland

    Fata, Jimmie E.; Leco, Kevin J.; Voura, Evelyn B.; Hoi-Ying E Yu; Waterhouse, Paul; Murphy, Gillian; Moorehead, Roger A.; Khokha, Rama

    2001-01-01

    The proapoptotic proteinase inhibitor TIMP-3 is the only molecule of this family thought to influence cell death. We examined epithelial apoptosis in TIMP-3–deficient mice during mammary gland involution. Lactation was not affected by the absence of TIMP-3, but glandular function, as measured by gland-to-body weight ratio and production of β-casein, was suppressed earlier during post-lactational involution than in controls. Histological examination revealed accelerated lumen collapse, alveola...

  3. Do myoepithelial cells hold the key for breast tumorprogression?

    Polyak, Kornelia; Hu, Min

    2005-11-18

    Mammary myoepithelial cells have been the foster child of breast cancer biology and have been largely ignored since they were considered to be less important for tumorigenesis than luminal epithelial cells from which most of breast carcinomas are thought to arise. In recent years as our knowledge in stem cell biology and the cellular microenvironment has been increasing myoepithelial cells are slowly starting to gain more attention. Emerging data raise the hypothesis if myoepithelial cells play a key role in breast tumor progression by regulating the in situ to invasive carcinoma transition and if myoepithelial cells are part of the mammary stem cell niche. Paracrine interactions between myoepithelial and luminal epithelial cells are known to be important for cell cycle arrest, establishing epithelial cell polarity, and inhibiting migration and invasion. Based on these functions normal mammary myoepithelial cells have been called ''natural tumor suppressors''. However, during tumor progression myoepithelial cells seem to loose these properties and eventually they themselves diminish as tumors become invasive. Better understanding of myoepithelial cell function and their role in tumor progression may lead to their exploitation for cancer therapeutic and preventative measures.

  4. Deficiency of Pten accelerates mammary oncogenesis in MMTV-Wnt-1 transgenic mice

    Crane Allison

    2001-01-01

    Full Text Available Abstract Background Germline mutations in the tumor suppressor PTEN predispose human beings to breast cancer, and genetic and epigenetic alterations of PTEN are also detected in sporadic human breast cancer. Germline Pten mutations in mice lead to the development of a variety of tumors, but mammary carcinomas are infrequently found, especially in mice under the age of six months. Results To better understand the role of PTEN in breast tumor development, we have crossed Pten heterozygous mice to MMTV-Wnt-1 transgenic mice that routinely develop ductal carcinomas in the mammary gland. Female Wnt-1 transgenics heterozygous for Pten developed mammary tumors earlier than Wnt-1 transgenics that were wild type for Pten. In most tumors arising in Pten heterozygotes, the Pten wild-type allele was lost, suggesting that cells lacking Pten function have a growth advantage over cells retaining a wild type allele. Tumors with LOH contained high levels of activated AKT/PKB, a downstream target of the PTEN/PI3K pathway. Conclusions An animal model has been developed in which the absence of Pten collaborates with Wnt-1 to induce ductal carcinoma in the mammary gland. This animal model may be useful for testing therapies specific for tumors deregulated in the PTEN/PI3K/AKT pathway.

  5. Luteolin suppresses development of medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumors in Sprague-Dawley rats.

    Cook, Matthew T; Mafuvadze, Benford; Besch-Williford, Cynthia; Ellersieck, Mark R; Goyette, Sandy; Hyder, Salman M

    2016-02-01

    Postmenopausal women undergoing hormone-replacement therapy containing both progestins and estrogens are at an increased risk of developing breast cancer compared with women taking estrogen alone. We recently demonstrated that medroxyprogesterone acetate, a progestin commonly used for hormone-replacement therapy, accelerates development of mammary carcinogenesis in 7,12-dimethylbenz(a)anthracene‑treated Sprague-Dawley rats. Synthetic antiprogestins used to block the deleterious effects of progestins, are themselves associated with toxic side-effects. In order to circumvent this, we used the aforementioned model to identify less toxic natural compounds that may prevent the development of progestin-accelerated tumors. Luteolin, a naturally-occurring flavonoid commonly found in fruits and vegetables, has previously been shown to possess anticancer properties. In our studies, both low (1 mg/kg) and high (25 mg/kg) doses of luteolin significantly suppressed progestin-dependent increases in tumor incidence, while increasing tumor latency and reducing the occurrence of large (>300 mm3) mammary tumors. However, an intermediate dose of luteolin (10 mg/kg), while suppressing the development of large tumors, did not affect either tumor incidence or latency. Immunohistochemical analysis of tumor tissues revealed that all concentrations of luteolin (1, 10, and 25 mg/kg) significantly reduced levels of VEGF within tumors. The suppressive effects of luteolin on tumor incidence and volume, together with its ability to reduce VEGF and blood vessels, persisted even after treatment was terminated. This suggests that luteolin possesses anti‑angiogenic properties which could mechanistically explain its capacity to control tumor progression. Thus luteolin may be a valuable, non-toxic, naturally-occurring anticancer compound which may potentially be used to combat progestin-accelerated mammary tumors. PMID:26719029

  6. Activation of Akt1 accelerates carcinogen-induced tumorigenesis in mammary gland of virgin and post-lactating transgenic mice

    Data from in vivo and in vitro studies suggest that activation of Akt regulates cell survival signaling and plays a key role in tumorigenesis. Hence, transgenic mice were created to explore the oncogenic role of Akt1 in the development of mammary tumors. The transgenic mice were generated by expressing myristoylated-Akt1 (myr-Akt1) under the control of the MMTV-LTR promoter. The carcinogen 7, 12 dimethyl-1,2-benzanthracene (DMBA) was used to induce tumor formation. The MMTV driven myr-Akt1 transgene expression was detected primarily in the mammary glands, uterus, and ovaries. The expression level increased significantly in lactating mice, suggesting that the response was hormone dependent. The total Akt expression level in the mammary gland was also higher in the lactating mice. Interestingly, the expression of MMTVmyr-Akt1 in the ovaries of the transgenic mice caused significant increase in circulating estrogen levels, even at the post-lactation stage. Expression of myr-Akt1 in mammary glands alone did not increase the frequency of tumor formation. However, there was an increased susceptibility of forming mammary tumors induced by DMBA in the transgenic mice, especially in mice post-lactation. Within 34 weeks, DMBA induced mammary tumors in 42.9% of transgenic mice post-lactation, but not in wild-type mice post-lactation. The myr-Akt1 mammary tumors induced by DMBA had increased phosphorylated-Akt1 and showed strong expression of estrogen receptor (ERα) and epidermal growth factor receptor (EGFR). In addition, Cyclin D1 was more frequently up-regulated in mammary tumors from transgenic mice compared to tumors from wild-type mice. Overexpression of Cyclin D1, however, was not completely dependent on activated Akt1. Interestingly, mammary tumors that had metastasized to secondary sites had increased expression of Twist and Slug, but low expression of Cyclin D1. In summary, the MMTVmyr-Akt1 transgenic mouse model could be useful to study mechanisms of ER

  7. Mammary tumors

    Mammary neoplasia is one of the more common malignancies affecting domestic species. Despite their importance, they are often over- diagnosed, undertreated and subject to several misconceptions propagated by veterinarians and pet owners alike. Mammary neoplasia is the most frequent tumor type encountered in the female accounting for almost half of all malignancies reported. The canine has the highest incidence of mammary tumors of all domestic species. In the dog, about 65 percent of mammary tumors are benign mixed tumors, and 25 percent are carcinomas. The rest are adenomas, myoepitheliomas, and malignant mixed tumors. The age distribution of mammary tumors closely follows the age distribution of most tumors in the dog. Mammary tumors are rare in dogs 2 years old, but incidence begins to increase sharply at approximately 6 years of age. Median age at diagnosis is about 10 years. No breed predilection has been consistently reported

  8. Hyperproduction of Hyaluronan in Neu-Induced Mammary Tumor Accelerates Angiogenesis through Stromal Cell Recruitment : Possible Involvement of Versican/PG-M

    Koyama, Hiroshi; Hibi, Terumasa; Isogai, Zenzo; Yoneda, Masahiko; Fujimori, Minoru; Amano, Jun; Kawakubo, Masatomo; Kannagi, Reiji; Kimata, Koji; Taniguchi, Shun’ichiro; Itano, Naoki

    2007-01-01

    Elevated concentrations of hyaluronan are often associated with human breast cancer malignancy. Here, we investigated the roles of hyaluronan in carcinogenesis and cancer progression using the mouse mammary tumor virus (MMTV)-Neu transgenic model of spontaneous breast cancer. Conditional transgenic mice that express murine hyaluronan synthase 2 (Has2) by Cre-mediated recombination were generated and crossed with the MMTV-Neu mice. In expressing Cre recombinase under the control of the MMTV pr...

  9. Mammary carcinoma diagnostics and therapy

    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.

  10. Mammary epithelial cell

    Kass, Laura; Erler, Janine Terra; Dembo, Micah;

    2007-01-01

    mammary gland. During breast development and cancer progression, the extracellular matrix is dynamically altered such that its composition, turnover, processing and orientation change dramatically. These modifications influence mammary epithelial cell shape, and modulate growth factor and hormonal...... organization, and promote cell invasion and survival. In this review, we discuss the role of stromal-epithelial interactions in normal and malignant mammary epithelial cell behavior. We specifically focus on how dynamic modulation of the biochemical and biophysical properties of the extracellular matrix elicit...

  11. Mammary gland stem cells

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

    2011-01-01

    understood. The mouse is a widely used model of mammary gland development, both directly by studying the mouse mammary epithelial cells themselves and indirectly, by studying development, morphogenesis, differentiation and carcinogenesis of xenotransplanted human breast epithelium in vivo. While in early...... 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....

  12. Accelerator

    The invention claims equipment for stabilizing the position of the front covers of the accelerator chamber in cyclic accelerators which significantly increases accelerator reliability. For stabilizing, it uses hydraulic cushions placed between the electromagnet pole pieces and the front chamber covers. The top and the bottom cushions are hydraulically connected. The cushions are disconnected and removed from the hydraulic line using valves. (J.P.)

  13. Soy isoflavone exposure through all life stages accelerates 17β-estradiol-induced mammary tumor onset and growth, yet reduces tumor burden, in ACI rats.

    Möller, Frank Josef; Pemp, Daniela; Soukup, Sebastian T; Wende, Kathleen; Zhang, Xiajie; Zierau, Oliver; Muders, Michael H; Bosland, Maarten C; Kulling, Sabine E; Lehmann, Leane; Vollmer, Günter

    2016-08-01

    There is an ongoing debate whether the intake of soy-derived isoflavones (sISO) mediates beneficial or adverse effects with regard to breast cancer risk. Therefore, we investigated whether nutritional exposure to a sISO-enriched diet from conception until adulthood impacts on 17β-estradiol (E2)-induced carcinogenesis in the rat mammary gland (MG). August-Copenhagen-Irish (ACI) rats were exposed to dietary sISO from conception until postnatal day 285. Silastic tubes containing E2 were used to induce MG tumorigenesis. Body weight, food intake, and tumor growth were recorded weekly. At necropsy, the number, position, size, and weight of each tumor were determined. Plasma samples underwent sISO analysis, and the morphology of MG was analyzed. Tumor incidence and multiplicity were reduced by 20 and 56 %, respectively, in the sISO-exposed rats compared to the control rats. Time-to-tumor onset was shortened from 25 to 20 weeks, and larger tumors developed in the sISO-exposed rats. The histological phenotype of the MG tumors was independent of the sISO diet received, and it included both comedo and cribriform phenotypes. Morphological analyses of the whole-mounted MGs also showed no diet-dependent differences. Lifelong exposure to sISO reduced the overall incidence of MG carcinomas in ACI rats, although the time-to-tumor was significantly shortened. PMID:26861028

  14. Immunoglobins in mammary secretions

    Hurley, W L; Theil, Peter Kappel

    2013-01-01

    Immunoglobulins secreted in colostrum and milk by the lactating mammal are major factors providing immune protection to the newborn. Immunoglobulins in mammary secretions represent the cumulative immune response of the lactating animal to exposure to antigenic stimulation that occurs through...... immunoglobulins found in mammary secretions in the context of their diversity of structure, origin, mechanisms of transfer, and function....

  15. Research on the Changes of Endocrine Hormones in Mammary Cancer and Hyperplasia of Mammary Glands

    CHEN Chengqi

    2002-01-01

    Objective Based on a comparison of endocrine hormones between patients of mammary cancer and those of hyperplasia of mammary glands, a preliminary analysis of the interaction between endocrine hormones and the immune system was oonducted. Methods The experiment involved 50 cases of mammary cancer and hyperplasia of mammary glands each.Blood samples were taken from pre - menopausal and menopausal patients; six kinds of hypophyseal hommones(PRL, GH, TSH,ACTH, FSH and LH) and three kinds of sex hormones ( E2,P and T) were subjected to RIA tests.Results Wilcoxon matchpaired assay and normal approximation of the experiment indicated that the FSH level before pre - menopause and the ACTH level during menopause in patients with mammary canoer were higher that those of patients suffering hyperplasia of mamary glands. Conclusion Statistics show the the normal rhythm between endocrine hormones and the immune system is disrupted in mammary cancer patients, the feedback mechanism of the hypothalamo- hypophyseal- adrenal system is maladjusted,resulting in inhibition of the immune function. Female hormones induce the gene mutation and the sensitivity of the cells is increased, resulting in a significant acceleration of the hyperplasia of cancer cells.

  16. A mammary repopulating cell population characterized in mammary anlagen reveals essential mammary stroma for morphogenesis.

    Song, Jiazhe; Xue, Kai; She, Ji; Ding, Fangrong; Li, Song; Shangguan, Rulan; Dai, Yunping; Du, Liying; Li, Ning

    2014-09-10

    The cells with mammary repopulating capability can achieve mammary gland morphogenesis in a suitable cellular microenvironment. Using cell surface markers of CD24, CD29 and CD49f, mouse mammary repopulating unit (MRU) has been identified in adult mammary epithelium and late embryonic mammary bud epithelium. However, embryonic MRU remains to be fully characterized at earlier mammary anlagen stage. Here we isolated discrete populations of E14.5 mouse mammary anlagen cells. Only Lin(-)CD24(med)CD29(+) cell population was predicted as E14.5 MRU by examining their capacities of forming mammosphere and repopulating cleared mammary fat pad in vivo. However, when we characterized gene expressions of this E14.5 cell population by comparing with adult mouse MRU (Lin(-)CD24(+)CD29(hi)), the gene profiling of these two cell populations exhibited great differences. Real-time PCR and immunostaining assays uncovered that E14.5 Lin(-)CD24(med)CD29(+) cell population was a heterogeneous stroma-enriched cell population. Then, limiting dilutions and single-cell assays also confirmed that E14.5 Lin(-)CD24(med)CD29(+) cell population possessed low proportion of stem cells. In summary, heterogeneous Lin(-)CD24(med)CD29(+) cell population exhibited mammary repopulating ability in E14.5 mammary anlagen, implying that only suitable mammary stroma could enable mammary gland morphogenesis, which relied on the interaction between rare stem cells and microenvironment. PMID:24954407

  17. Mammary Glands: Developmental Changes

    The mammary gland progresses from the accumulation of a few cells in the embryonic ectoderm to a highly arborescent tubulo-alveolar gland capable of secreting a highly nutritious product for consumption. Throughout this progression, various changes occur during each developmental stage: prenatal, pr...

  18. Canine mammary tumors - clinical survey

    Elena Atanaskova Petrov; Ksenija Ilievska; Plamen Trojacanec; Irena Celeska; Goran Nikolovski; Ivica Gjurovski; Toni Dovenski

    2014-01-01

    Mammary tumours are the second most frequent neoplasia in dogs, mainly affecting older female patients. Approximately 50% of the mammary tumours are malignant with high percentage of mortality if not treated in time. The aim of this study was to analyze the data of canine patients with mammary tumours, to evaluate the type of tumours, as well as the relationship between tumour incidence and dogs’ age, reproductive cycle and sterilization. The survey was used to retrieve the information in the...

  19. Bone Morphogenetic Proteins stimulate mammary fibroblasts to promote mammary carcinoma cell invasion.

    Philip Owens

    Full Text Available Bone Morphogenetic Proteins (BMPs are secreted cytokines that are part of the Transforming Growth Factor β (TGFβ superfamily. BMPs have been shown to be highly expressed in human breast cancers, and loss of BMP signaling in mammary carcinomas has been shown to accelerate metastases. Interestingly, other work has indicated that stimulation of dermal fibroblasts with BMP can enhance secretion of pro-tumorigenic factors. Furthermore, treatment of carcinoma-associated fibroblasts (CAFs derived from a mouse prostate carcinoma with BMP4 was shown to stimulate angiogenesis. We sought to determine the effect of BMP treatment on mammary fibroblasts. A large number of secreted pro-inflammatory cytokines and matrix-metallo proteases (MMPs were found to be upregulated in response to BMP4 treatment. Fibroblasts that were stimulated with BMP4 were found to enhance mammary carcinoma cell invasion, and these effects were inhibited by a BMP receptor kinase antagonist. Treatment with BMP in turn elevated pro-tumorigenic secreted factors such as IL-6 and MMP-3. These experiments demonstrate that BMP may stimulate tumor progression within the tumor microenvironment.

  20. Mammary tuberculosis: percutaneous treatment of a mammary tuberculous abscess

    It is currently very rare to find mammary involvement in cases of tuberculosis, in either primary or secondary form. Diagnosis is classically clinical and microbiological, and the basic techniques used in imaging diagnosis are mammography and ultrasound. Computed tomography may define the involvement of the thoracic wall in those cases which present as mammary masses adhering to deep levels, and is also able to evaluate accompanying pulmonary disease, if it is present. Traditionally, treatment has consisted of quadrantectomy and specific antibiotic therapy. We present a case of tuberculous mammary abscess secondary to pulmonary disease, which was treated by percutaneous drainage controlled by CT and specific antibiotic therapy. We revise the diagnosis, differential diagnosis and treatment of mammary tuberculosis. (orig.)

  1. Mammary tuberculosis: percutaneous treatment of a mammary tuberculous abscess

    Romero, C.; Carreira, C.; Cereceda, C.; Pinto, J. [Servicio de Radiologia, Hospital Virgen de la Salud, Toledo (Spain); Lopez, R.; Bolanos, F. [Servicio de Cirugia, Hospital Virgen de la Salud, Toledo (Spain)

    2000-03-01

    It is currently very rare to find mammary involvement in cases of tuberculosis, in either primary or secondary form. Diagnosis is classically clinical and microbiological, and the basic techniques used in imaging diagnosis are mammography and ultrasound. Computed tomography may define the involvement of the thoracic wall in those cases which present as mammary masses adhering to deep levels, and is also able to evaluate accompanying pulmonary disease, if it is present. Traditionally, treatment has consisted of quadrantectomy and specific antibiotic therapy. We present a case of tuberculous mammary abscess secondary to pulmonary disease, which was treated by percutaneous drainage controlled by CT and specific antibiotic therapy. We revise the diagnosis, differential diagnosis and treatment of mammary tuberculosis. (orig.)

  2. Canine mammary tumors - clinical survey

    Elena Atanaskova Petrov

    2014-10-01

    Full Text Available Mammary tumours are the second most frequent neoplasia in dogs, mainly affecting older female patients. Approximately 50% of the mammary tumours are malignant with high percentage of mortality if not treated in time. The aim of this study was to analyze the data of canine patients with mammary tumours, to evaluate the type of tumours, as well as the relationship between tumour incidence and dogs’ age, reproductive cycle and sterilization. The survey was used to retrieve the information in the period of two years from the patient data base of the University Veterinary Hospital at the Faculty of Veterinary medicine in Skopje. Patients included in this survey were subjected to routine clinical investigation and additional laboratory tests (cytological examination, x-rays imaging, CBC and biochemical profile, histopathology of the tumor samples. Aged female patients (12 – 13 years are the most susceptible category for development of mammary tumours. The reproductive history showed that five of the patients with malignant mammary tumourshave never whelped and were not treated with any exogenous hormones. Malignant tumours (adenocarcinoma were diagnosed in 90% of the patients. Three patients died due to lung metastasis. Late diagnosis is one of the major problems that results in lethal outcome due to lung metastases. Since ovarian steroids play an important role in the aetiology, the most effective prevention of mammary tumoursis elective ovariectomy of the bitch at an early age.

  3. Insulin receptors in the mammary gland

    Insulin binding studies were conducted using mammary membrane preparations to further the authors understanding of insulin's role in regulating mammary metabolism, particularly ruminant mammary metabolism. Specific objectives were to: (1) characterize insulin binding to bovine mammary microsomes and determine if the specificity and kinetics of binding indicate the presence of insulin receptors in bovine mammary gland; (2) examine and compare insulin binding by liver and mammary microsomes of the pig and dairy cow; (3) examine insulin binding to bovine milk fat globule membranes (MFGM) and evaluate this model's usefulness in assessing insulin receptor regulation in the mammary gland of the cow; (4) examine the effect of dietary fat in insulin binding by rat mammary and liver microsomes. The specificity and kinetics of 125I-insulin binding of bovine mammary microsomes indicated the presence of insulin receptors in bovine mammary gland. Bovine liver and mammary microsomes specifically bound less 125I-insulin than did the corresponding porcine microsomes, and mammary microsomes, regardless of species, specifically bound less 125I-insulin than did liver microsomes. These differences in binding suggest differences in insulin responsiveness between pigs and cattle, as well as between the liver and mammary glands

  4. Prepubertal exposure to cow's milk reduces susceptibility to carcinogen-induced mammary tumorigenesis in rats

    Nielsen, Tina Skau; Khan, Galam; Davis, Jennifer;

    2011-01-01

    Cow's milk contains high levels of estrogens, progesterone and insulin-like growth factor 1 (IGF-1), all of which are associated with breast cancer. We investigated whether prepubertal milk exposure affects mammary gland development and carcinogenesis in rats. Sprague-Dawley rats were given either...... whole milk or tap water to drink from postnatal day (PND) 14 to PND 35, and thereafter normal tap water. Mammary tumorigenesis was induced by administering 7,12-dimethylbenz[a]anthracene on PND 50. Milk exposure increased circulating E2 levels on PND 25 by 10-fold (p < 0.001) and accelerated vaginal...... opening, which marks puberty onset, by 2.5 days (p < 0.001). However, rats exposed to milk before puberty exhibited reduced carcinogen-induced mammary carcinogenesis; that is, their tumor latency was longer (p < 0.03) and incidence was lower (p < 0.05) than in the controls. On PND 25 and 50, mammary...

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

    Mandrup, Karen; Hass, Ulla; Christiansen, Sofie;

    2012-01-01

    , 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......, indicating progressed development of mammary glands when exposed to oestrogens early in life. However, laboratories use different parameters to evaluate the development of mammary glands, making studies difficult to compare. Moreover, studies of whole mounts in Wistar rats are lacking. In the present study......‐pubertal Wistar rats, mammary gland development was accelerated after perinatal oestrogen exposure with increase in size, density and number of terminal end buds (TEBs). In female rats, the most sensitive parameters were the distance to the fifth gland, the relative growth towards the lymph node and the overall...

  6. Mammary blood flow and nutrient uptake

    Farmer, Chantal; Trottier, N.L.; Dourmad, Jean-Yves

    2015-01-01

    Sow milk is the major source of nutrients for suckling piglets and taking into account the large litter sizes of our current sow genotypes, it is imperative to maximize nutrient use by the mammary gland. The amount of nutrients available to mammary tissue is dependent upon the concentrations of nutrients in blood and the rate of its flow to the lactating glands. Nutrient availability to the udder may be estimated by measuring mammary arteriovenous differences, and mammary blood flow can be me...

  7. Mammary carcinoma diagnostics and therapy; Diagnostik und Therapie des Mammakarzinoms

    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.

  8. Mammary carcinosarcoma in cat: a case report

    J.D.G. Paniago; A.L.S. Vieira; N.M. Ocarino; S.A. França; C. Malm; Cassali, G.D.; R. Serakides

    2010-01-01

    A case of mammary carcinosarcoma is reported in a 13-year-old, mixed breed female cat, which was not spayed and had not received contraceptives. The patient presented extensive and coalescent nodules in all mammary glands. Based on the histological and immunohistochemical findings, the diagnosis of mammary carcinosarcoma was confirmed.

  9. Canine mammary tumours, an overview.

    Sleeckx, N; de Rooster, H; Veldhuis Kroeze, E J B; Van Ginneken, C; Van Brantegem, L

    2011-12-01

    Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Although the prevalence of these tumours decreases in regions where preventive ovari(ohyster)ectomy is performed, it remains an important disease entity in veterinary medicine. Moreover, treatment options are limited in comparison with human breast cancer. Nevertheless, recent human treatment protocols might have potential in bitches suffering from CMTs. PMID:21645126

  10. Differential immunization as a method to discover new antigens that are associated with tumour progression and metastasis; Differentielle Immunisierungstechniken als eine Methode um neue Antigene zu entdecken, die mit Tumorprogression und Metastasierung assoziiert sind

    Mengwasser, J.

    2003-04-01

    M receptor in B-cells. Their function is unknown. Even though both proteins are found in the nucleus and in the cytoplasm, the antibody I isolated binds in immunofluorescent studies to prohibitin/BAP37 only in the cytoplasm. This may indicate a modified conformation possibly associated with a modified function. I am the first who could show a cell surface expression or a secretion for these proteins. (orig.) [German] Bei der von mir durchgefuehrten subtraktiven Immunisierung konnte ich spezifische Antikoerper isolieren, die Antigene auf der hochmetastasierenden Zelllienie AT6.1 erkennen. Diese Antigene scheinen ebenfalls eine Funktion in der Tumorprogression zu spielen, da die Antikoerper in Versuchen das Tumorwachstum deutlich reduzieren konnten. Die Identifizierung und Charakterisierung dieser Antigene wird uns weitere Hinweise fuer die erforderlichen Veraenderungen von Tumorzellen auf ihrer Zelloberflaeche geben. Es besteht immer noch ein eklatanter Mangel an Molekuelen, die im Serum nachgewiesen werden koennen und die Diagnose von Krebs in fruehen Stadien ermoeglichen, aber auch den Verlauf einer Therapie ueberwachen koennen. In der von uns entwickelten Serum Immunisierung wurde von mir versucht, dem Ansatz, solche Molekuele zu identifizieren, gerecht zu werden. Ich konnte acht Antikoerper isolieren, die Molekuele im Serum erkennen, die vom Tumor sezerniert oder abgespalten werden. Einer dieser Antikoerper erschien als besonders interessant, da das von ihm gebundene Antigen auf vielen humanen Tumorzelllinien exprimiert wird. Es gelang mir, die Antigene zu identifizieren, die sich als Prohibitin und BAP37 herausstellten. Ueber die Funktionen beider Proteine ist noch nicht viel bekannt. Als Komplex wird ihnen eine Rolle in der Mitochondrienmembran als Chaperon zur Stabilisierung mitochondrialer Proteine zugesprochen. Prohibitin soll im Nukleus mit RB interagieren und somit die Funktion von E2F modulieren. BAP37 soll unter dem Namen REA (repressor of estrogen activity) das

  11. Ectopic mammary tissue in vulva

    Đorđević Momčilo

    2008-01-01

    Full Text Available Background. Ectopic mammary gland tissue is a residual tissue that persists during the embryologic development along ectodermal primitive milk streaks. Incomplete involution anywhere along the primitive milk streak can result in accessory or ectopic mammary tissue. Case report. A woman, 27-year old, admitted to Obstetrics and Gynecology Clinic Kragujevac for surgery, of goose-egg size, vulva tumor, of elastic consistency. Menarche started in 12 years of age, with the regular menstrual cycle, without previous gynecological diseases. The woman had one pregnancy terminated by cesarean section because of the multiple (twin pregnancy. Excision of the tumor was completely done in the total endotracheal anesthesia. Pathohistologic (PH findings was: Dysplasia fibrosa cystica simplex mammae, with focuses of sclerosing adenosis. Expression of estrogen (ER and progesterone receptors (PR were positive. Conclusion. Ectopic mammary tissue in vulva in adult period is very rarely seen, and can be changed pathologically as well as normally positioned breast tissue into benign cystic changes, benign tumors, adenomas and fibroadenomas and tumors. Cells with low ER/PR receptor level grow independently of estrogene stimulation and they could be resistant to hormonal therapy effects.

  12. Mammary neoplasms of the bitch.

    Cotchin, E

    1958-01-01

    In this paper, the interrelationships of the neoplasms of the canine mammary gland are investigated. These neoplasms are a group of tumors of a great variety of histological structure and sometimes of uncertain histogenesis. Particular attention is given to the histogenesis of the mucoid, cartilaginous, and bony elements. From 1950-56, a macroscopic and histological examination of mammary neoplasms from 424 bitches (2-17 years of age) was made. The tumors from 381 bitches were removed surgically while the others came from 43 bitches who were examined postmortem. Of the 160 tumors whose location was recorded, 105 occurred in the 2 hinder glands, 19 in the middle glands, and 46 in one or another of the 2 anterior glands. 186 of the 424 bitches bore malignant mammary tumors (87 carcinomas, 73 sarcomas, 27 complex malignant tumors) and 249 had benign tumors (19 simple and 230 complex). 40 of the benign complex tumors contained bone, an additional 63 contained cartilage but no bone, and 67 showed mucoid tissue but no cartilage or bone. It is suggested that there is a predominant proliferation of myoepithelial cells which tend to become embedded in a mucoid or chondroid matrix. The bone in the tumors appears to be formed by endochondral ossification of preformed cartilage, or by intramembranous ossification in the connective tissue of the tumor. Metastases were present in 41 of the 424 bitches. PMID:12311486

  13. Mammary Hypertrophy in an Ovariohysterectomized Cat

    Pukay, B.P.; Stevenson, D.A.

    1983-01-01

    A four year old ovariohysterectomized domestic short-haired cat under treatment for behavioral urine spraying and idiopathic alopecia developed mammary gland hypertrophy following treatment with megestrol acetate. Withdrawal of the progestin and treatment with androgen failed to cause regression of the hypertrophy. The affected mammary gland was surgically excised and recovery was uneventful.

  14. Effects of maternal dietary exposure to cadmium during pregnancy on mammary cancer risk among female offspring

    Jennifer Davis

    2013-01-01

    Full Text Available Background: Since heavy metal cadmium is an endocrine disrupting chemical, we investigated whether maternal exposure to cadmium during the pregnancy alters mammary tumorigenesis among female offspring. Methods: From gestation day 10 to day 19, pregnant rat dams were fed modified American Institute of Nutrition (AIN93G diet containing 39% energy from fat (baseline diet, or the baseline diet containing moderate (75 μg/kg of feed or high (150 μg/kg cadmium levels. Some dams were injected with 10 μg 17β-estradiol (E2 daily between gestation days 10 and 19. Results: Rats exposed to a moderate cadmium dose in utero were heavier and exhibited accelerated puberty onset. Both moderate and high cadmium dose led to increased circulating testosterone levels and reduced the expression of androgen receptor in the mammary gland. The moderate cadmium dose mimicked the effects of in utero E2 exposure on mammary gland morphology and increased both the number of terminal end buds and pre-malignant hyperplastic alveolar nodules (HANs, but in contrast to the E2, it did not increase 7, 12-dimethylbenz (a anthracene-induced mammary tumorigenesis. Conclusions: The effects of in utero cadmium exposure were dependent on the dose given to pregnant dams: Moderate, but not high, cadmium dose mimicked some of the effects seen in the in utero E2 exposed rats, such as increased HANs in the mammary gland.

  15. Mammary and extramammary Paget's disease*

    Lopes, Lauro Lourival; Lopes, Ione Maria Ribeiro Soares; Lopes, Lauro Rodolpho Soares; Enokihara, Milvia M. S. S.; Michalany, Alexandre Osores; Matsunaga, Nobuo

    2015-01-01

    Paget's disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen's disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget's disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent. PMID:25830993

  16. Breast metastases primitive extra mammary

    Less than 3% of all breast cancers originate from a primitive extra mammary. In 40% of cases it is the first manifestation of the primitive properly studied but 80% are associated with widely disseminated disease. It typically presents as a nodule on external quadrant s painful in half the cases. The majority (60%) of metastases derived from breast contralateral breast tumors are believed to via the lymphatic system. of the ; extra mammary the most common tumors are melanoma; hematologic and neuroendocrine. Although some imaging characteristics can guide diagnosis is histological. Cytology has good performance in experienced hands; but up to 25% of cases there may be difficulty in establishing diagnosis. Treatment depends on the type of tumor. Mastectomy should not be practiced or axillary clearance routine as is generally the context of disease disseminated. Radiation therapy may be useful for local control. It has been proposed laser ablation but no experience with it. The overall prognosis is bad. For a man of 45 with a breast metastasis occurs only a clear cell carcinoma of the kidney

  17. Mammary and extramammary Paget's disease.

    Lopes Filho, Lauro Lourival; Lopes, Ione Maria Ribeiro Soares; Lopes, Lauro Rodolpho Soares; Enokihara, Milvia M S S; Michalany, Alexandre Osores; Matsunaga, Nobuo

    2015-01-01

    Paget's disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen's disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget's disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent. PMID:25830993

  18. Mouse mammary tumor biology: a short history.

    Cardiff, Robert D; Kenney, Nicholas

    2007-01-01

    For over a century, mouse mammary tumor biology and the associated Mouse mammary tumor virus (MMTV) have served as the foundation for experimental cancer research, in general, and, in particular, experimental breast cancer research. Spontaneous mouse mammary tumors were the basis for studies of the natural history of neoplasia, oncogenic viruses, host responses, endocrinology, and neoplastic progression. However, lacking formal proof of a human mammary tumor virus, the preeminence of the mouse model faded in the 1980s. Since the late 1980s, genetically engineered mice (GEM) have proven extremely useful for studying breast cancer and have become the animal model for human breast cancer. Hundreds of mouse models of human breast cancer have been developed since the first demonstration, in 1984, that the mouse mammary gland could be molecularly targeted and used to test the oncogenicity of candidate human genes. Now, very few scientists can avoid using a mouse model to test the biology of their favorite gene. The GEM have attracted a new generation of molecular and cellular biologists eager to apply their skills to these surrogates of the human disease. Newcomers often enter the field without an appreciation of the origins of mouse mammary tumor biology and the basis for many of the prevailing concepts. Our purpose in writing this short history of mouse mammary tumor biology is to provide a historical perspective for the benefit of the newcomers. If Einstein was correct in that "we stand on the shoulders of giants," the neophytes should meet their giants. PMID:17433908

  19. Evolution of somatic mutations in mammary tumors in transgenic mice is influenced by the inherited genotype

    Li Yi

    2004-06-01

    Full Text Available Abstract Background MMTV-Wnt1 transgenic mice develop mammary hyperplasia early in development, followed by the appearance of solitary mammary tumors with a high proportion of cells expressing early lineage markers and many myoepithelial cells. The occurrence of tumors is accelerated in experiments that activate FGF proto-oncogenes or remove the tumor suppressor genes Pten or P53, implying that secondary oncogenic events are required for progression from mammary hyperplasia to carcinoma. It is not known, however, which oncogenic pathways contribute to Wnt1-induced tumorigenesis – further experimental manipulation of these mice is needed. Secondary events also appear to be required for mammary tumorigenesis in MMTV-Neu transgenic mice because the transgene in the tumors usually contains an acquired mutation that activates the Neu protein-tyrosine kinase. Methods cDNA or DNA from the mammary glands and mammary tumors from MMTV-Wnt1, MMTV-Wnt1/p53-/-, MMTV-Neu transgenic mice, and newly generated MMTV-Wnt1/MMTV-Neu bitransgenic mice, was sequenced to seek activating mutations in H-Ras, K-Ras, and N-Ras genes, or in the MMTV-Neu transgene. In addition, tumors from bitransgenic animals were examined to determine the cellular phenotype. Results We found activating mutations at codons 12, 13, and 61 of H-Ras in just over half of the mammary tumors in MMTV-Wnt1 transgenic mice, and we confirmed the high frequency of activating mutations of Neu in tumors in MMTV-Neu transgenic mice. Tumors appeared earlier in bitransgenic MMTV-Wnt1/MMTV-Neu mice, but no Ras or MMTV-Neu mutations were found in these tumors, which were phenotypically similar to those arising in MMTV-Wnt1 mice. In addition, no Ras mutations were found in the mammary tumors that arise in MMTV-Wnt1 transgenic mice lacking an intact P53 gene. Conclusions Tumorigenic properties of cells undergoing functionally significant secondary mutations in H-Ras or the MMTV-Neu transgene allow selection

  20. Absence of proteins related to murine mammary tumour virus polypeptides in rat mammary tumours

    Since normal rat DNA contains sequences which hybridize with the genome of the murine mammary tumour virus (MuMTV), it is possible that a related virus would play a role in mammary carcinogenesis in rats. The authors screened a number of rat mammary tumours for antigens related to the MuMTV polypeptides gp52 and p28 by means of a radioimmunoassay. (Auth.)

  1. Mammary gland tumors in captive African hedgehogs.

    Raymond, J T; Gerner, M

    2000-04-01

    From December 1995 to July 1999, eight mammary gland tumors were diagnosed in eight adult captive female African hedgehogs (Atelerix albiventris). The tumors presented as single or multiple subcutaneous masses along the cranial or caudal abdomen that varied in size for each hedgehog. Histologically, seven of eight (88%) mammary gland tumors were malignant. Tumors were classified as solid (4 cases), tubular (2 cases), and papillary (2 cases). Seven tumors had infiltrated into the surrounding stroma and three tumors had histologic evidence of neoplastic vascular invasion. Three hedgehogs had concurrent neoplasms. These are believed to be the first reported cases of mammary gland tumors in African hedgehogs. PMID:10813628

  2. Myoepithelial cells in canine mammary tumours.

    Sánchez-Céspedes, Raquel; Millán, Yolanda; Guil-Luna, Silvia; Reymundo, Carlos; Espinosa de Los Monteros, Antonio; Martín de Las Mulas, Juana

    2016-01-01

    Mammary tumours are the most common neoplasms of female dogs. Compared to mammary tumours of humans and cats, myoepithelial (ME) cell involvement is common in canine mammary tumours (CMT) of any subtype. Since ME cell involvement in CMT influences both histogenetic tumour classification and prognosis, correct identification of ME cells is important. This review describes immunohistochemical methods for identification of canine mammary ME cells used in vivo. In addition, phenotypic and genotypic methods to isolate ME cells for in vitro studies to analyse tumour-suppressor protein production and gene expression are discussed. The contribution of ME cells to both histogenetic classifications and the prognosis of CMT is compared with other species and the potential use of ME cells as a method to identify carcinoma in situ is discussed. PMID:26639832

  3. Selenium in human mammary carcinogenesis

    Overvad, Kim; Grøn, P.; Langhoff, Otto;

    1991-01-01

    In a case-referent study on the possible role of selenium in human mammary carcinogenesis, serum selenium was found to be 79 +/- 12 micrograms/l in 66 cases and 81 +/- 12 micrograms/l in 93 referents. An internal trend in serum selenium was observed among cases (TNM stage I 81 +/- 11 micrograms....../l and TNM stage II 76 +/- 13 micrograms selenium/l), indicating disease-mediated changes. The evaluation of selenium as a risk indicator in human breast cancer was therefore restricted to TNM stage I patients (n = 36). Multiple logistic regression analyses including variables associated with selenium...... levels revealed no association between selenium levels and breast cancer risk....

  4. Caratterizzazione molecolare dei tumori mammari Tripli Negativi

    Bertoni, Ramona

    2013-01-01

    I tumori mammari “Tripli Negativi” (TN) rappresentano circa il 15% di tutti i tumori mammari. Sono tumori clinicamente molto aggressivi, con una prognosi infausta: alta è l’incidenza di metastasi e di recidiva locale. Attualmente per pazienti affetti da questo tumore non esiste uno schema terapeutico efficace, né una terapia molecolare, infatti questi tumori non esprimono il recettore estrogenico (ER), quello progestinico (PGR) e il recettore HER2 (da cui il nome Tripli Negativi). Nella quasi...

  5. The mammary cellular hierarchy and breast cancer

    Oakes, Samantha R.; Gallego-Ortega, David; Ormandy, Christopher J.

    2014-01-01

    Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The mammary epithelium, unlike the hematopoietic cellular hierarchy, sits in a complex niche where communication between epithelial cells and signals from the systemic hormonal milieu, as well as from extra-cellular matrix, influence cell fate decisions and contribute to tissue homeostasis. We review the discovery, definition and ...

  6. Stem Cells and the Mammary Microenvironment

    Booth, Brian W.; Boulanger, Corinne A.; Smith, Gilbert H.

    2008-01-01

    An entire mammary epithelial outgrowth, capable of full secretory differentiation, may comprise the progeny of a single cellular antecedent. This conclusion is based upon the maintenance of retroviral insertion sites within the somatic DNA of successive transplant generations derived from a single mammary fragment. In addition, dissociation of these clonal dominant glands and implantation of dispersed cells at limiting dilution demonstrated that both duct-limited and lobule-limited outgrowths...

  7. Mammary stem cells have myoepithelial cell properties

    Prater, Michael D.; Petit, Val?rie; Russell, I Alasdair; Giraddi, Rajshekhar; Shehata, Mona; Menon, Suraj; Schulte, Reiner; Kalajzic, Ivo; Rath, Nicola; Olson, Michael F.; Metzger, Daniel; Faraldo, Marisa M.; Deugnier, Marie-Ange; Glukhova, Marina A.; Stingl, John

    2014-01-01

    Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt acin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepi...

  8. Regulation of leptin in involution of mammary gland

    LI Meng; LI Qingzhang

    2007-01-01

    Leptin, a protein hormone produced and secreted predominantly by white adipose tissue, has a critical role in the regulation and coordination of energy metabolism. Leptin is produced in the mammary gland by the fat tissue or by the mammary epithelium. In vitro study has shown that leptin triggers apoptosis in mammary epithelial cells. Mammary gland involution is characterized by extensive apoptosis of the epithelial cells. At the onset of involution, STAT3 is specifically activated. Various studies show that leptin act as a paracrine and autocrin factor to influence mammary epithelial cell proliferation and differentiation. This paper reviewed the function of leptin to the involution of mammary gland.

  9. Spleen tyrosine kinase regulates mammary epithelial cell proliferation in mammary glands of dairy cows.

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

    2016-05-01

    Spleen tyrosine kinase (SYK) is a nonreceptor tyrosine kinase that has been considered a hematopoietic cell-specific signal transducer involved in cell proliferation and differentiation. However, the role of SYK in normal mammary gland is still poorly understood. Here we show that SYK is expressed in mammary glands of dairy cows. Expression of SYK was higher in dry period mammary tissues than in lactating mammary tissues. Knockdown and overexpression of SYK affected dairy cow mammary epithelial cell proliferation as well as the expression of signal molecules involved in proliferation, including protein kinase B (PKB, also known as AKT1), p42/44 mitogen-activated protein kinase (MAPK), and signal transducer and activator of transcription 5 (STAT5). Dual-luciferase reporter assay showed that SYK increased the transcriptional activity of the AKT1 promoter, and cis-elements within the AKT1 promoter region from -439 to -84 bp mediated this regulation. These results suggest that SYK affects mammary epithelial cell proliferation by activating AKT1 at the transcriptional level in mammary glands of dairy cows, which is important for the mammary remodeling process in dry cows as well as for increasing persistency of lactation in lactating cows. PMID:26947307

  10. 4-Vinylcyclohexene Diepoxide (VCD) Inhibits Mammary Epithelial Differentiation and Induces Fibroadenoma Formation in Female Sprague Dawley Rats

    Wright, Laura E; Frye, Jennifer B.; Lukefahr, Ashley L; Marion, Samuel L.; Hoyer, Patricia B.; Besselsen, David G.; Funk, Janet L.

    2011-01-01

    4-Vinylcyclohexene diepoxide (VCD), an occupational chemical that targets ovarian follicles and accelerates ovarian failure in rodents, was used to test the effect of early-onset reproductive senescence on mammary fibroadenoma formation. One-month female Sprague Dawley rats were dosed with VCD (80 mg/kg or 160 mg/kg) and monitored for 22 months for persistent estrus and tumor development. Only high-dose VCD treatment accelerated the onset of persistent estrus relative to controls. However, bo...

  11. Development of Spontaneous Mammary Tumors in BALB/c p53 Heterozygous Mice : A Model for Li-Fraumeni Syndrome

    Kuperwasser, Charlotte; Hurlbut, Gregory D; Kittrell, Frances S; Dickinson, Ellen S.; Laucirica, Rudy; Medina, Daniel; Naber, Stephen P.; Jerry, D. Joseph

    2000-01-01

    Breast cancer is the most frequent tumor type among women in the United States and in individuals with Li-Fraumeni syndrome. The p53 tumor suppressor gene is altered in a large proportion of both spontaneous breast malignancies and Li-Fraumeni breast cancers. This suggests that loss of p53 can accelerate breast tumorigenesis, yet p53-deficient mice rarely develop mammary tumors. To evaluate the effect of p53 loss on mammary tumor formation, the p53null allele was back-crossed onto the BALB/c ...

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

    Gyorki, D.E.; Asselin-Labat, M.L.; Rooijen, van, J.; 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 influence have not been determined. Here we have explored a role for macrophages in regulating mammary stem cell (MaSC) activity, by assessing the ability of MaSCs to reconstitute a mammary gland ...

  13. Classification and grading of canine malignant mammary tumors

    Abbas Tavasoly; Hannaneh Golshahi; Annahita Rezaie; Mohammad Farhadi

    2013-01-01

    Histological grading is a good parameter to stratify tumors according to their biological aggressiveness. The Elston and Ellis grading method in humans, invasive ductal breast carcinomas and other invasive tumors are routinely used. The aims of this study were classification of mammary gland tumors and also application of a human grading method in canine mammary carcinoma. The samples included 37 tumors of mammary glands. Mammary tumors were carcinomas (n = 32) and sarcomas (n = 5). The carci...

  14. Wnt4 is not sufficient to induce lobuloalveolar mammary development

    Pelegri Francisco; Clark Rod J; Kim Young; Alexander Caroline M

    2009-01-01

    Abstract Background Brisken et al (2000) showed that Wnt4 null mammary glands were deficient in early lobuloalveolar mammary outgrowth during pregnancy, and implicated Wnt4 as an effector for the progesterone-induced mammary growth program. Though ectopic Wnt1 signaling is known to be mitogenic and oncogenic, no endogenously expressed Wnt ligands have ever been directly implicated in mammary growth and morphogenesis. Therefore, we generated conditional transgenic mice to test whether Wnt4 can...

  15. Positional Variations in Mammary Gland Development and Cancer

    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...

  16. Cell-cell interactions promote mammary epithelial cell differentiation

    1985-01-01

    Mammary epithelium differentiates in a stromal milieu of adipocytes and fibroblasts. To investigate cell-cell interactions that may influence mammary epithelial cell differentiation, we developed a co-culture system of murine mammary epithelium and adipocytes and other fibroblasts. Insofar as caseins are specific molecular markers of mammary epithelial differentiation, rat anti-mouse casein monoclonal antibodies were raised against the three major mouse casein components to study this interac...

  17. 9 CFR 310.17 - Inspection of mammary glands.

    2010-01-01

    ... mammary glands and diseased mammary glands of cattle, sheep, swine, and goats shall be removed without... accordance with the provisions of part 311 of this subchapter. (c) Lactating mammary glands of cattle, sheep... as “Brucellosis reactors” or as “Mastitis elimination cows” shall be condemned....

  18. Effects of BRCA1 Transgene Expression on Murine Mammary Gland Development and Mutagen-Induced Mammary Neoplasia

    Hoshino, Arichika; Yee, Cindy J; Campbell, Mel; Woltjer, Randall L.; Townsend, Rebecca L.; van Meer, Riet; Shyr, Yu; Holt, Jeffrey T.; Harold L. Moses; Jensen, Roy A.

    2007-01-01

    To characterize the role of BRCA1 in mammary gland development and tumor suppression, a transgenic mouse model of BRCA1 overexpression was developed. Using the mouse mammary tumor virus (MMTV) promoter/enhancer, transgenic mice expressing human BRCA1 or select mutant controls were generated. Transgenic animals examined during adolescence were shown to express the human transgene in their mammary glands. The mammary glands of 13-week-old virgin homozygous MMTV-BRCA1 mice presented the morpholo...

  19. Of Microenvironments and Mammary Stem Cells

    LaBarge, Mark A; Petersen, Ole W; Bissell, Mina J

    2007-06-01

    In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit.

  20. PTEN deficiency: a role in mammary carcinogenesis

    The PTEN gene is often mutated in primary human tumors and cell lines, but the low rate of somatic PTEN mutation in human breast cancer has led to debate over the role of this tumor suppressor in this disease. The involvement of PTEN in human mammary oncogenesis has been implicated from studies showing that germline PTEN mutation in Cowden disease predisposes to breast cancer, the frequent loss of heterozygosity at the PTEN locus, and reduced PTEN protein levels in sporadic breast cancers. To assay the potential contribution of PTEN loss in breast tumor promotion, Li et al. [1] crossed Pten heterozygous mice with mouse mammary tumor virus-Wnt-1 transgenic (Wnt-1 TG, Pten+/-) mice. Mammary ductal carcinoma developed earlier in Wnt-1 TG, Pten+/- mice than in mice bearing either genetic change alone, and showed frequent loss of the remaining wild-type PTEN allele. These data indicate a role for PTEN in breast tumorigenesis in an in vivo model

  1. Mammary stem cells have myoepithelial cell properties.

    Prater, Michael D; Petit, Valérie; Alasdair Russell, I; Giraddi, Rajshekhar R; Shehata, Mona; Menon, Suraj; Schulte, Reiner; Kalajzic, Ivo; Rath, Nicola; Olson, Michael F; Metzger, Daniel; Faraldo, Marisa M; Deugnier, Marie-Ange; Glukhova, Marina A; Stingl, John

    2014-10-01

    Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt actin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using two independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage-tracing approach we follow the progeny of myoepithelial cells that express α-smooth muscle actin and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy. PMID:25173976

  2. Mammary tumorigenesis by radiation and its prevention

    Onoda, Makoto; Suzuki, Keiko; Inano, Hiroshi [National Inst. of Radiological Sciences, Chiba (Japan)

    1999-06-01

    Since the breast cancer in women emerged as an important risk associated with exposure to ionizing radiation, we have investigated to clarify the relationship between the induction of mammary tumors by irradiation and the developmental stage of the mammary glands that regulated by the action of endocrine hormones. Besides the radiation, epidemiological studies showed that the process of biosynthesis/metabolism of steroid hormones and hyperlipidemia may be associated with an increased risk of mammary carcinogenesis. In this context, we have undertaken investigations to evaluate the anti-carcinogenic activities of dehydroepiandrosterone (DHEA), a major secretory steroid of the adrenal glands, bezafibrate (BEZF), an anti-hyperlipidemic drug derived from clofibrate, and simvastatin (SIMV), a prodrug of a specific inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, against diethylstilbestrol (DES)-dependent promotion/progression of rat mammary tumors initiated by {gamma}-rays. Pregnant Wistar-MS rats received whole-body irradiation with 2.6 Gy of {gamma}-rays from a {sup 60}Co source at day-20 of pregnancy. The mother rats were fed a diet containing either 0.6% DHEA, 0.15% BEZF or 0.03% SIMV beginning immediately after weaning. They were then implanted subcutaneously with a pellet of DES (3 mg/pellet) in the interscapular area 30 days after termination of nursing and were observed for 1 year for detection of palpable mammary tumors starting from the time of pellet implantation. The administration of dietary DHEA, BEZF or SIMV together with DES implantation in rats irradiated in late pregnancy significantly decreased the total incidence of mammary tumors to 35%, 27% and 36%, respectively, for the 1 year period, while higher tumor incidence (96%, 90% and 88%) was observed in rats fed controldiet. However, neither the number of mammary tumors per tumor-bearing rat nor the latency period in the drug treated groups was different from that observed in the control group

  3. Mammary tumorigenesis by radiation and its prevention

    Since the breast cancer in women emerged as an important risk associated with exposure to ionizing radiation, we have investigated to clarify the relationship between the induction of mammary tumors by irradiation and the developmental stage of the mammary glands that regulated by the action of endocrine hormones. Besides the radiation, epidemiological studies showed that the process of biosynthesis/metabolism of steroid hormones and hyperlipidemia may be associated with an increased risk of mammary carcinogenesis. In this context, we have undertaken investigations to evaluate the anti-carcinogenic activities of dehydroepiandrosterone (DHEA), a major secretory steroid of the adrenal glands, bezafibrate (BEZF), an anti-hyperlipidemic drug derived from clofibrate, and simvastatin (SIMV), a prodrug of a specific inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, against diethylstilbestrol (DES)-dependent promotion/progression of rat mammary tumors initiated by γ-rays. Pregnant Wistar-MS rats received whole-body irradiation with 2.6 Gy of γ-rays from a 60Co source at day-20 of pregnancy. The mother rats were fed a diet containing either 0.6% DHEA, 0.15% BEZF or 0.03% SIMV beginning immediately after weaning. They were then implanted subcutaneously with a pellet of DES (3 mg/pellet) in the interscapular area 30 days after termination of nursing and were observed for 1 year for detection of palpable mammary tumors starting from the time of pellet implantation. The administration of dietary DHEA, BEZF or SIMV together with DES implantation in rats irradiated in late pregnancy significantly decreased the total incidence of mammary tumors to 35%, 27% and 36%, respectively, for the 1 year period, while higher tumor incidence (96%, 90% and 88%) was observed in rats fed controldiet. However, neither the number of mammary tumors per tumor-bearing rat nor the latency period in the drug treated groups was different from that observed in the control group. From histological

  4. Quantitative of murine mammary tumor virus-related RNA in mammary tissues of low- and high-mammary-tumor-incidence mouse strains.

    Marcus, S L; Smith, S. W.; Sarkar, N H

    1981-01-01

    Lactating mammary glands and hormonally induced mammary tumors of BALB/c mice from three geographically separated breeding colonies were examined by molecular hybridization, using murine mammary tumor virus (MuMTV) cDNA representing the entire viral genome to determine the amount of MuMTV-related RNA expressed in these tissues. The RNA extracted from these tissues by the classical sodium dodecyl sulfate-pronase, phenol-chloroform procedure (method 1) contained barely detectable levels of MuMT...

  5. MIBI-99mTc mammary scintigraphy

    121 patients suspected of breast cancer were studied with MIBI-99mTc to evaluate the suitability of the mammary scintigraphy in patients with doubtful cancer diagnosis.The results show 93 % sensitivity and 95 % specificity and indicate the usefulness of this procedure to increase the accuracy of the diagnosis

  6. Mouse Mammary Tumor Virus Molecular Biology and Oncogenesis

    Susan R. Ross

    2010-09-01

    Full Text Available Mouse mammary tumor virus (MMTV, which was discovered as a milk‑transmitted, infectious cancer-inducing agent in the 1930s, has been used since that time as an animal model for the study of human breast cancer. Like other complex retroviruses, MMTV encodes a number of accessory proteins that both facilitate infection and affect host immune response. In vivo, the virus predominantly infects lymphocytes and mammary epithelial cells. High level infection of mammary epithelial cells ensures efficient passage of virus to the next generation. It also results in mammary tumor induction, since the MMTV provirus integrates into the mammary epithelial cell genome during viral replication and activates cellular oncogene expression. Thus, mammary tumor induction is a by-product of the infection cycle. A number of important oncogenes have been discovered by carrying out MMTV integration site analysis, some of which may play a role in human breast cancer.

  7. TGF-β1 promotes bovine mammary fibroblast proliferation through the ERK 1/2 signalling pathway.

    Gao, Yuanyuan; Wang, Yuping; Li, Yingying; Xia, Xiaojing; Zhao, Shuang; Che, Yanyi; Sun, Yingying; Lei, Liancheng

    2016-07-01

    The abnormal proliferation of bovine mammary fibroblasts (BMFBs) impairs mammary gland development and lactation. Severe manifestations develop into breast fibrosis, leading to the culling of cows and causing serious losses to the dairy industry. Transforming growth factor β1 (TGF-β1) is an important modulator of cell proliferation and extracellular matrix formation; however, limited information is available on BMFBs. In this study, a convenient and stable culture method for BMFBs was established. Treatment with 5 ng/mL of TGF-β1 significantly promoted the proliferation of BMFBs and accelerated the cell cycle. TGF-β1 stimulation for up to 12 h significantly increased the relative ERK1/2 mRNA expression and enhanced the protein expression of p-ERK1/2 and cyclin D1. Conversely, the ERK1/2 inhibitor PD98059 blocked these TGF-β1 effects. Further exploration using a mouse model showed that TGF-β1 significantly increased the proportion of fibroblasts and accelerating the cell transition from the G1 to G2/M phases. In addition, TGF-β1 enhanced the expression of fibrosis markers, α-SMA and I Collagen, which could be blocked efficiently by the PD98059 in mouse mammary gland. Finally, immunofluorescence analysis confirmed that TGF-β1 promoted fibroblast proliferation in healthy dairy cows after normal long-term dietary corn straw roughage supplementation. It is suggested that the diet may promote mammary fibroblast proliferation by raising the level of TGF-β1. Our study provides new insights into how nutrition causes undesirable changes in mammary gland structure. PMID:27063575

  8. Mammary development and breast cancer: the role of stem cells

    Ercan, C.; J. van Diest, P.; Vooijs, M.

    2011-01-01

    The mammary gland is a highly regenerative organ that can undergo multiple cycles of proliferation, lactation and involution, a process controlled by stem cells. The last decade much progress has been made in the identification of signaling pathways that function in these stem cells to control self-renewal, lineage commitment and epithelial differentiation in the normal mammary gland. The same signaling pathways that control physiological mammary development and homeostasis are also often fou...

  9. Prenatal Morphogenesis of Mammary Glands in Mouse and Rabbit

    Propper, Alain Y.; Howard, Beatrice A; Veltmaat, Jacqueline M.

    2013-01-01

    Our understanding of prenatal morphogenesis of mammary glands has recently greatly advanced. This review focuses on morphogenesis proper, as well as cellular processes and tissue interactions involved in the progression of the embryonic mammary gland through sequential morphogenic stages in both the mouse and rabbit embryo. We provide a synthesis of both historical and more recent studies of embryonic mammary gland development, as well as arguments to revise old concepts about mechanisms of m...

  10. Mammary leptin synthesis, milk leptin and their putative physiological roles

    Bonnet, Muriel; Delavaud, Carole; Laud, Karine; Gourdou, Isabelle; Leroux, Christine; Djiane, Jean; Chilliard, Yves

    2002-01-01

    International audience This paper reviews data on mammary leptin and leptin receptor gene expression as well as on blood and milk leptin levels during the pregnancy-lactation cycle in humans, rodents and ruminants, with the aim of better understanding milk leptin origin and functions. The few published papers report that leptin may be produced by different cell types in the mammary tissue, and may act as a paracrine factor on mammary epithelial cell proliferation, differentiation and/or ap...

  11. Mfge8 is critical for mammary gland remodeling during involution

    Atabai, Kamran; Fernandez, Rafael; Huang, Xiaozhu; Ueki, Iris; Kline, Ahnika; LI, YONG; Sadatmansoori, Sepid; Smith-Steinhart, Christine; Zhu, Weimin; Pytela, Robert; Werb, Zena; Sheppard, Dean

    2005-01-01

    Apoptosis is a critical process in normal mammary gland development and the rapid clearance of apoptotic cells prevents tissue injury associated with the release of intracellular antigens from dying cells. Milk fat globule-EGF-factor 8 (Mfge8) is a milk glycoprotein that is abundantly expressed in the mammary gland epithelium and has been shown to facilitate the clearance of apoptotic lymphocytes by splenic macrophages. We report that mice with disruption of Mfge8 had normal mammary gland dev...

  12. Histological and Morphometric Study of Lactating Mammary Glands in Sows

    Svätoslav Hluchý; Norbert Bolcsó

    2011-01-01

    This work deals with the quantitative histological morphometric description of the mammary glands of sows during the stage of lactation. As experimental animals were used White meat breed pigs (5 animals) kept in standard conditions VÚŽV in Nitra. After killing the animals we sampled mammary glands and have them processed by conventional histological and histochemical methods. Morphometric methods, we found that glandular parenchyma of mammary glands of sows consists of a lobules width 615.28...

  13. Hedgehog and Gli Signaling in Embryonic Mammary Gland Development

    Lee, May Yin; Sun, Li; Veltmaat, Jacqueline M.

    2013-01-01

    The first mouse mutation associated with a heritable defect in embryonic mammary gland development was Extratoes. It represents a functional null-mutation of the gene encoding Gli3, which is best known as a transcription factor mediating canonical Hedgehog (Hh) signaling. Here we review the roles of Hh and Gli proteins in murine embryonic mammary development. We propose that an off-state for Hh signaling, mediated by Gli3-repressor, is determinant for induction of a mammary instead of hair fo...

  14. Tissue proteomics of the human mammary gland

    Moreira, José Manuel Alfonso; Cabezón, Teresa; Gromova, Irina;

    2010-01-01

    phenotypes of the different cell subpopulations present in normal human mammary tissue, partly due to the formidable heterogeneity of mammary tissue, but also due to limitations of the current proteomic technologies. Work in our laboratories has attempted to address in a systematic fashion some of these...... biomarker discovery program. We review and present new data on the putative cell-progenitor marker cytokeratin 15 (CK15), and describe a novel marker, dihydropyriminidase-related protein 3 (DRP3) that in combination with CK15 and other well known proteins were used to define molecular phenotypes of normal...... human breast epithelial cells and their progenitors in resting acini, lactating alveoli, and large collecting ducts of the nipple. Preliminary results are also presented concerning DRP3 positive usual ductal hyperplasias (UDHs) and on single cell layer columnar cells (CCCs). At least two bona fide...

  15. Atherosclerosis and the internal mammary arteries

    One hundred and fifty patients with coronary artery disease (CAD), 14 (9.3%) of whom had coexisting peripheral vascular disease, underwent bilateral internal mammary arteriography to study the incidence and extent of atherosclerosis in these vessels. Significant atherosclerosis of the internal mammary arteries (IMAs) was present in three patients (2%), of whom one had coexisting peripheral vascular disease. Lesions in the IMAs were found either proximally, close to the origin or distally, around the terminal bifurcation. Six of the 14 patients with peripheral vascular disease (4% of total subjects) had significant atherosclerosis of the brachiocephalic arteries. Atherosclerotic involvement of the IMA is very unusual and rarely interferes with the use of these vessels for coronary bypass. More common, however, is atherosclerosis of the subclavian arteries, a contraindication for IMA grafting if the lesion is proximal to the IMA origin. (orig.)

  16. Alpha basic crystallin expression in canine mammary tumors

    Guvenc, Tolga; Gulbahar, Mustafa Yavuz; YARIM, Murat; Kabak, Yonca Betil; Karayigit, Onder; Sozmen, Mahmut

    2012-01-01

    The aim of this study was to evaluate prognostic and/or diagnostic factors of canine mammary tumors by immunohistochemically analyzing the expression of alpha basic crystallin (αB-c). For this, formalin-fixed, paraffin-embedded blocks of 51 naturally-occurring canine mammary tumors (11 benign and 40 malignant) were used. Tissue from eight normal canine mammary glands were served as a control. Immunohistochemically, in the control mammary tissues, a few luminal epithelial cells were αB-c posit...

  17. Morphogenesis of Mammary Glands in Buffalo (Bubalus bubalis)

    Amit Challana; Anuradha Gupta; Neelam Bansal; Varinder Uppal

    2014-01-01

    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 we...

  18. Mammary gland stem cells: More puzzles than explanations

    Suneesh Kaimala; Suneesh Kaimala; Satish Kumar

    2012-06-01

    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. At present, Lin–CD29hiCD49fhiCD24+/modSca-1– cells of the mammary gland have been reported to be enriched with MaSCs. We suggest that the inclusion of stem cell markers like Oct4, Sox2, Nanog and the mammary gland differentiation marker BRCA-1 may further narrow down the search for MaSCs. In addition, we have discussed some of the other unresolved puzzles on the mammary gland stem cells, such as their similarities and/or differences with mammary cancer stem cells, use of milk as source of mammary stem cells and the possibility of in vitro differentiation of embryonic stem (ES) cells into functional mammary gland structures in this review. Nevertheless, it is the lack of identity for a MaSC that is curtailing the advances in some of the above and other related areas.

  19. Epigenetic regulation of LSD1 during mammary carcinogenesis

    Wu, Yadi; Zhou, Binhua P

    2014-01-01

    Inheritable epigenetic regulation is integral to the dynamic control of gene expression under different stimuli for cellular homeostasis and disease progression. Histone methylation is a common and important type of chromatin modification. LSD1, the first known histone lysine-specific demethylase, operates as a key component of several corepressor complexes during development and in disease states. In this review, we focus on the regulation of LSD1 in mammary carcinogenesis. LSD1 plays a role in promoting mammary tumor metastasis and proliferation and in maintaining mammary cancer stem cells. Therefore, LSD1 represents a viable therapeutic target for effective treatment of mammary carcinogenesis. PMID:27308339

  20. Ultrasound appearance of chronic mammary duct ectasia

    Mammary duct ectasia (MDE), also called periductal mastitis, mammary dysplasia, or plasma cell mastitis, is a benign condition of the mammary gland first described by Haagensen in 1951. The etiology of MDE is unknown and its pathogenesis still controversial; the periductal inflammation could be either the cause or the result of dilated damaged ducts. The process is usually bilateral and asymptomatic, with only a small percentage of patients presenting with symptoms that may include long course of tumour formation, usually subareolar breast lumps, nipple discharge, nipple retraction, mastalgia, and mammary abscess or fistulas. Mammographic presentation of MDE is well known; its features include periductal calcification, benign intraductal calcification, and retroareolar duct dilatation. The periductal calcification results from dystrophic calcification and forms calcified rings or very dense, oval, elongated calcifications, each with a central lucency representing the dilated duct. Intraductal calcifications of duct ectasia represent inspissated intraductal material and are typically of uniform high density, often needle-like, and occasionally branching. Occasionally, there are no mammographic findings, and the diagnosis must rely on sonographic features. Appearance of MDE on ultrasonography (US) depends on the stage of the disease and the contents of the dilated ducts. The acute presentation has been demonstrated in the literature more often than has its chronic counterpart. In the former, duct content can vary from anechoic to isoechoic with surrounding fatty tissue. In chronic MDE, episodes of inflammation are longer. This tends to result in secretions that have a more solid, cheesy texture, partly due to cholesterol crystals, foam cells, and inflammatory cells. For both types of MDE, the appearance can mimic high-grade ductal carcinoma in situ (DCIS) on US. In this essay, 2 chronic MDE cases are presented and their US appearance discussed. Our goal is to explore

  1. Ultrasound appearance of chronic mammary duct ectasia

    Duchesne, N. [Ottawa Hospital, Dept. of Radiology, Ottawa, Ontario (Canada)]. E-mail: nathalie_duchesne_22@yahoo.ca; Skolnik, S. [Univ. of Toronto, Dept. of Family Medicine, Toronto, Ontario (Canada); Bilmer, S. [Ottawa Hospital, Dept. of Radiology, Ottawa, Ontario (Canada)

    2005-12-15

    Mammary duct ectasia (MDE), also called periductal mastitis, mammary dysplasia, or plasma cell mastitis, is a benign condition of the mammary gland first described by Haagensen in 1951. The etiology of MDE is unknown and its pathogenesis still controversial; the periductal inflammation could be either the cause or the result of dilated damaged ducts. The process is usually bilateral and asymptomatic, with only a small percentage of patients presenting with symptoms that may include long course of tumour formation, usually subareolar breast lumps, nipple discharge, nipple retraction, mastalgia, and mammary abscess or fistulas. Mammographic presentation of MDE is well known; its features include periductal calcification, benign intraductal calcification, and retroareolar duct dilatation. The periductal calcification results from dystrophic calcification and forms calcified rings or very dense, oval, elongated calcifications, each with a central lucency representing the dilated duct. Intraductal calcifications of duct ectasia represent inspissated intraductal material and are typically of uniform high density, often needle-like, and occasionally branching. Occasionally, there are no mammographic findings, and the diagnosis must rely on sonographic features. Appearance of MDE on ultrasonography (US) depends on the stage of the disease and the contents of the dilated ducts. The acute presentation has been demonstrated in the literature more often than has its chronic counterpart. In the former, duct content can vary from anechoic to isoechoic with surrounding fatty tissue. In chronic MDE, episodes of inflammation are longer. This tends to result in secretions that have a more solid, cheesy texture, partly due to cholesterol crystals, foam cells, and inflammatory cells. For both types of MDE, the appearance can mimic high-grade ductal carcinoma in situ (DCIS) on US. In this essay, 2 chronic MDE cases are presented and their US appearance discussed. Our goal is to explore

  2. Mammary Fibromatosis: Sonographic Features and Pathologic Correlations

    Jung, Hae Kyoung; Ko, Kyung Hee; Rho, Ji Young; Kang, Hye Yoon [Cha University College of Medicine, Pocheon (Korea, Republic of); Kim, Eun Kyung [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2010-09-15

    The purpose of this study was to determine if the sonographic features of mammary fibromatosis had correlation with the pathologic findings. We identified four cases of fibromatosis of the breast at our institution over a 10-year period. The patients were all women, and they ranged from 25 to 48 years of age (mean, 34.3 years). All four patients complained of palpable breast masses and were subsequently diagnosed with mammary fibromatosis. We retrospectively reviewed their imaging findings. Mammography obtained in one patient revealed architectural distortion. On sonography, all four cases showed spiculated, irregular, hypoechoic masses that could not be differentiated from malignant lesions. After surgical excision and vacuum assisted biopsy of the masses in four patients, there was no recurrence on clinical or sonographic follow-up over a 13-36 month period. Although mammary fibromatosis is a very rare condition, it should be included in the differential diagnosis when an un-calcified, spiculated, irregular and hypoechoic masses are encountered on breast sonography

  3. PKA signaling drives mammary tumorigenesis through Src.

    Beristain, A G; Molyneux, S D; Joshi, P A; Pomroy, N C; Di Grappa, M A; Chang, M C; Kirschner, L S; Privé, G G; Pujana, M A; Khokha, R

    2015-02-26

    Protein kinase A (PKA) hyperactivation causes hereditary endocrine neoplasias; however, its role in sporadic epithelial cancers is unknown. Here, we show that heightened PKA activity in the mammary epithelium generates tumors. Mammary-restricted biallelic ablation of Prkar1a, which encodes for the critical type-I PKA regulatory subunit, induced spontaneous breast tumors characterized by enhanced type-II PKA activity. Downstream of this, Src phosphorylation occurs at residues serine-17 and tyrosine-416 and mammary cell transformation is driven through a mechanism involving Src signaling. The phenotypic consequences of these alterations consisted of increased cell proliferation and, accordingly, expansion of both luminal and basal epithelial cell populations. In human breast cancer, low PRKAR1A/high SRC expression defines basal-like and HER2 breast tumors associated with poor clinical outcome. Together, the results of this study define a novel molecular mechanism altered in breast carcinogenesis and highlight the potential strategy of inhibiting SRC signaling in treating this cancer subtype in humans. PMID:24662820

  4. Oxytocin binding sites in bovine mammary tissue

    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.

  5. Gata-3 Negatively Regulates the Tumor-Initiating Capacity of Mammary Luminal Progenitor Cells and Targets the Putative Tumor Suppressor Caspase-14 ▿ §

    Asselin-Labat, Marie-Liesse; Sutherland, Kate D.; Vaillant, François; Gyorki, David E; Wu, Di; Holroyd, Sheridan; Breslin, Kelsey; Ward, Teresa; Shi, Wei; Bath, Mary L.; Deb, Siddhartha; Fox, Stephen B.; Smyth, Gordon K; Lindeman, Geoffrey J; Visvader, Jane E.

    2011-01-01

    The transcription factor Gata-3 is a definitive marker of luminal breast cancers and a key regulator of mammary morphogenesis. Here we have explored a role for Gata-3 in tumor initiation and the underlying cellular mechanisms using a mouse model of “luminal-like” cancer. Loss of a single Gata-3 allele markedly accelerated tumor progression in mice carrying the mouse mammary tumor virus promoter-driven polyomavirus middle T antigen (MMTV-PyMT mice), while overexpression of Gata-3 curtailed tum...

  6. CIRCADIAN CLOCK AND CELL CYCLE GENE EXPRESSION: IN MOUSE MAMMARY EPITHELIAL CELLS AND IN THE DEVELOPING MOUSE MAMMARY GLAND

    Metz, Richard P.; Qu, Xiaoyu; Laffin, Brian; Earnest, David; Porter, Weston W.

    2006-01-01

    Mouse mammary epithelial cells (HC-11) and mammary tissues were analyzed for developmental changes in circadian clock, cellular proliferation and differentiation marker genes. Expression of the clock genes, Per1 and Bmal1, were elevated in differentiated HC-11 cells whereas Per2 mRNA levels were higher in undifferentiated cells. This differentiation-dependent profile of clock gene expression was consistent with that observed in mouse mammary glands as Per1 and Bmal1 mRNA levels were elevated ...

  7. Key stages of mammary gland development: Molecular mechanisms involved in the formation of the embryonic mammary gland

    Hens, Julie R; Wysolmerski, John J

    2005-01-01

    The development of the embryonic mammary gland involves communication between the epidermis and mesenchyme and is coordinated temporally and spatially by various signaling pathways. Although many more genes are likely to control mammary gland development, functional roles have been identified for Wnt, fibroblast growth factor, and parathyroid hormone-related protein signaling. This review describes what is known about the molecular mechanisms that regulate embryonic mammary gland development.

  8. The cyclin-like protein Spy1/RINGO promotes mammary transformation and is elevated in human breast cancer

    Spy1 is a novel 'cyclin-like' activator of the G1/S transition capable of enhancing cell proliferation as well as inhibiting apoptosis. Spy1 protein levels are tightly regulated during normal mammary development and forced overexpression in mammary mouse models accelerates mammary tumorigenesis. Using human tissue samples, cell culture models and in vivo analysis we study the implications of Spy1 as a mediator of mammary transformation and breast cancer proliferation. We demonstrate that this protein can facilitate transformation in a manner dependent upon the activation of the G2/M Cdk, Cdk1, and the subsequent inhibition of the anti-apoptotic regulator FOXO1. Importantly, we show for the first time that enhanced levels of Spy1 protein are found in a large number of human breast cancers and that knockdown of Spy1 impairs breast cancer cell proliferation. Collectively, this work supports that Spy1 is a unique activator of Cdk1 in breast cancer cells and may represent a valuable drug target and/or a prognostic marker for subsets of breast cancers

  9. β1 integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli

    Li, Na; Zhang, Yu; Naylor, Matthew J.; Schatzmann, Franziska; Maurer, Francisca; Wintermantel, Tim; Schuetz, Gunther; Mueller, Ulrich; Streuli, Charles H; Hynes, Nancy E.

    2005-01-01

    Integrin–extracellular matrix interactions play important roles in the coordinated integration of external and internal cues that are essential for proper development. To study the role of β1 integrin in the mammary gland, Itgβ1flox/flox mice were crossed with WAPiCre transgenic mice, which led to specific ablation of β1 integrin in luminal alveolar epithelial cells. In the β1 integrin mutant mammary gland, individual alveoli were disorganized resulting from alterations in cell–basement membr...

  10. Claudin 7 expression and localization in the normal murine mammary gland and murine mammary tumors

    Claudins, membrane-associated tetraspanin proteins, are normally associated with the tight junctions of epithelial cells where they confer a variety of permeability properties to the transepithelial barrier. One member of this family, claudin 7, has been shown to be expressed in the human mammary epithelium and some breast tumors. To set the stage for functional experiments on this molecule, we examined the developmental expression and localization of claudin 7 in the murine mammary epithelium and in a selection of murine mammary tumors. We used real-time polymerase chain reaction, in situ mRNA localization, and immunohistochemistry (IHC) to examine the expression and localization of claudin 7. Frozen sections were examined by digital confocal microscopy for colocalization with the tight-junction protein ZO1. Claudin 7 was expressed constitutively in the mammary epithelium at all developmental stages, and the ratio of its mRNA to that of keratin 19 was nearly constant through development. By IHC, claudin 7 was located in the basolateral part of the cell where it seemed to be localized to discrete vesicles. Scant colocalization with the tight-junction scaffolding protein ZO1 was observed. Similar results were obtained from IHC of the airway epithelium and some renal tubules; however, claudin 7 did partly colocalize with ZO1 in EPH4 cells, a normal murine mammary cell line, and in the epididymis. The molecule was localized in the cytoplasm of MMTV-neu and the transplantable murine tumor cell lines TM4, TM10, and TM40A, in which its ratio to cytokeratin was higher than in the normal mammary epithelium. Claudin 7 is expressed constitutively in the mammary epithelium at approximately equal levels throughout development as well as in the murine tumors examined. Although it is capable of localizing to tight junctions, in the epithelia of mammary gland, airway, and kidney it is mostly or entirely confined to punctate cytoplasmic structures, often near the basolateral

  11. BALB/Mtv-Null Mice Responding to Strong Mouse Mammary Tumor Virus Superantigens Restrict Mammary Tumorigenesis▿

    Bhadra, Sanchita; Lozano, Mary M.; Dudley, Jaquelin P.

    2008-01-01

    The absence of endogenous mouse mammary tumor viruses (MMTVs) in the congenic mouse strain, BALB/Mtv-null, restricts the early steps of exogenous C3H MMTV infection, preventing the superantigen (Sag) response and mammary tumorigenesis. Here we demonstrate that BALB/Mtv-null mice also resist tumor induction by FM MMTV, which encodes a stronger Sag compared to C3H MMTV. In contrast to infections with C3H MMTV, Mtv-null mice show FM-MMTV Sag-specific responses comparable to those observed in sus...

  12. Can Accelerators Accelerate Learning?

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ)[1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

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

    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 ...

  14. Antitumor effect of magnetite nanoparticles in cat mammary adenocarcinoma

    Sincai, Mariana [Cell Biology-Histology Department, Faculty of Veterinary Medicine, Calea Aradului no.119, Timisoara 19000 (Romania)]. E-mail: msincai@yahoo.com; Ganga, Diana [Cell Biology-Histology Department, Faculty of Veterinary Medicine, Calea Aradului no.119, Timisoara 19000 (Romania); Ganga, Marius [Private Veterinary Practice, Timisoara (Romania); Argherie, Diana [Cell Biology-Histology Department, Faculty of Veterinary Medicine, Calea Aradului no.119, Timisoara 19000 (Romania); Bica, Doina [Laboratory of Magnetic Fluids, Center for Fundamental and Advanced Technical Research, Romanian Academy-Timisoara Branch (Romania)

    2005-05-15

    The antitumor effect of a magnetic fluid was studied after direct inoculation into cat mammary tumors. An external magnetic field was used to retain the nanoparticles in the tumor tissue. After 2 month, the mammary tumor regressed very much in size and the microscopic exam revealed that the tumor cells massively endocytosed magnetic nanoparticles and entered in lysis process.

  15. Antitumor effect of magnetite nanoparticles in cat mammary adenocarcinoma

    The antitumor effect of a magnetic fluid was studied after direct inoculation into cat mammary tumors. An external magnetic field was used to retain the nanoparticles in the tumor tissue. After 2 month, the mammary tumor regressed very much in size and the microscopic exam revealed that the tumor cells massively endocytosed magnetic nanoparticles and entered in lysis process

  16. Bovine Mammary Epithelial Cell Lineages and Parenchymal Development

    Mammary development proceeds from an aggregation of cells in the ventral ectoderm to the establishment of an elaborate tree of alveoli, ducts, and cisternae. However, despite abundant data on endocrine regulation of ruminant mammary growth, we know comparatively little about cell lineages, express...

  17. Huntingtin Regulates Mammary Stem Cell Division and Differentiation

    Salah Elias

    2014-04-01

    Full Text Available Little is known about the mechanisms of mitotic spindle orientation during mammary gland morphogenesis. Here, we report the presence of huntingtin, the protein mutated in Huntington’s disease, in mouse mammary basal and luminal cells throughout mammogenesis. Keratin 5-driven depletion of huntingtin results in a decreased pool and specification of basal and luminal progenitors, and altered mammary morphogenesis. Analysis of mitosis in huntingtin-depleted basal progenitors reveals mitotic spindle misorientation. In mammary cell culture, huntingtin regulates spindle orientation in a dynein-dependent manner. Huntingtin is targeted to spindle poles through its interaction with dynein and promotes the accumulation of NUMA and LGN. Huntingtin is also essential for the cortical localization of dynein, dynactin, NUMA, and LGN by regulating their kinesin 1-dependent trafficking along astral microtubules. We thus suggest that huntingtin is a component of the pathway regulating the orientation of mammary stem cell division, with potential implications for their self-renewal and differentiation properties.

  18. Huntingtin regulates mammary stem cell division and differentiation.

    Elias, Salah; Thion, Morgane S; Yu, Hua; Sousa, Cristovao Marques; Lasgi, Charlène; Morin, Xavier; Humbert, Sandrine

    2014-04-01

    Little is known about the mechanisms of mitotic spindle orientation during mammary gland morphogenesis. Here, we report the presence of huntingtin, the protein mutated in Huntington's disease, in mouse mammary basal and luminal cells throughout mammogenesis. Keratin 5-driven depletion of huntingtin results in a decreased pool and specification of basal and luminal progenitors, and altered mammary morphogenesis. Analysis of mitosis in huntingtin-depleted basal progenitors reveals mitotic spindle misorientation. In mammary cell culture, huntingtin regulates spindle orientation in a dynein-dependent manner. Huntingtin is targeted to spindle poles through its interaction with dynein and promotes the accumulation of NUMA and LGN. Huntingtin is also essential for the cortical localization of dynein, dynactin, NUMA, and LGN by regulating their kinesin 1-dependent trafficking along astral microtubules. We thus suggest that huntingtin is a component of the pathway regulating the orientation of mammary stem cell division, with potential implications for their self-renewal and differentiation properties. PMID:24749073

  19. Plasma accelerators

    Recently attention has focused on charged particle acceleration in a plasma by a fast, large amplitude, longitudinal electron plasma wave. The plasma beat wave and plasma wakefield accelerators are two efficient ways of producing ultra-high accelerating gradients. Starting with the plasma beat wave accelerator (PBWA) and laser wakefield accelerator (LWFA) schemes and the plasma wakefield accelerator (PWFA) steady progress has been made in theory, simulations and experiments. Computations are presented for the study of LWFA. (author)

  20. Linear Accelerators

    Vretenar, M

    2014-01-01

    The main features of radio-frequency linear accelerators are introduced, reviewing the different types of accelerating structures and presenting the main characteristics aspects of linac beam dynamics.

  1. Genetic mechanisms in Apc-mediated mammary tumorigenesis.

    Mari Kuraguchi

    2009-02-01

    Full Text Available Many components of Wnt/beta-catenin signaling pathway also play critical roles in mammary tumor development, yet the role of the tumor suppressor gene APC (adenomatous polyposis coli in breast oncongenesis is unclear. To better understand the role of Apc in mammary tumorigenesis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-cre and WAP-cre transgenic mice that express Cre-recombinase in mammary progenitor cells and lactating luminal cells, respectively. Only the K14-cre-mediated Apc heterozygosity developed mammary adenocarcinomas demonstrating histological heterogeneity, suggesting the multilineage progenitor cell origin of these tumors. These tumors harbored truncation mutation in a defined region in the remaining wild-type allele of Apc that would retain some down-regulating activity of beta-catenin signaling. Activating mutations at codons 12 and 61 of either H-Ras or K-Ras were also found in a subset of these tumors. Expression profiles of acinar-type mammary tumors from K14-cre; Apc(CKO/+ mice showed luminal epithelial gene expression pattern, and clustering analysis demonstrated more correlation to MMTV-neu model than to MMTV-Wnt1. In contrast, neither WAP-cre-induced Apc heterozygous nor homozygous mutations resulted in predisposition to mammary tumorigenesis, although WAP-cre-mediated Apc deficiency resulted in severe squamous metaplasia of mammary glands. Collectively, our results suggest that not only the epithelial origin but also a certain Apc mutations are selected to achieve a specific level of beta-catenin signaling optimal for mammary tumor development and explain partially the colon- but not mammary-specific tumor development in patients that carry germline mutations in APC.

  2. Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities.

    Janice B B Lam

    Full Text Available BACKGROUND: Adiponectin is an adipokine possessing beneficial effects on obesity-related medical complications. A negative association of adiponectin levels with breast cancer development has been demonstrated. However, the precise role of adiponectin deficiency in mammary carcinogenesis remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, MMTV-polyomavirus middle T antigen (MMTV-PyVT transgenic mice with reduced adiponectin expressions were established and the stromal effects of adiponectin haploinsufficiency on mammary tumor development evaluated. In mice from both FVB/N and C57BL/6J backgrounds, insufficient adiponectin production promoted mammary tumor onset and development. A distinctive basal-like subtype of tumors, with a more aggressive phenotype, was derived from adiponectin haplodeficient MMTV-PyVT mice. Comparing with those from control MMTV-PyVT mice, the isolated mammary tumor cells showed enhanced tumor progression in re-implanted nude mice, accelerated proliferation in primary cultures, and hyperactivated phosphatidylinositol-3-kinase (PI3K/Akt/beta-catenin signaling, which at least partly attributed to the decreased phosphatase and tensin homolog (PTEN activities. Further analysis revealed that PTEN was inactivated by a redox-regulated mechanism. Increased association of PTEN-thioredoxin complexes was detected in tumors derived from mice with reduced adiponectin levels. The activities of thioredoxin (Trx1 and thioredoxin reductase (TrxR1 were significantly elevated, whereas treatment with either curcumin, an irreversible inhibitor of TrxR1, or adiponectin largely attenuated their activities and resulted in the re-activation of PTEN in these tumor cells. Moreover, adiponectin could inhibit TrxR1 promoter-mediated transcription and restore the mRNA expressions of TrxR1. CONCLUSION: Adiponectin haploinsufficiency facilitated mammary tumorigenesis by down-regulation of PTEN activity and activation of PI3K

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

    Nørgaard, Jan Værum; Nielsen, Mette Olaf; Theil, Peter Kappel;

    2008-01-01

    mammary biopsies were collected on d -16, d - 6, d 5 and d 30 from parturition. Fetus weights, weight of mammary parenchyma, amount of mammary epithelium and rate of mammary cell proliferation increased from d -38 to d -6 from parturition, but was not significantly affected by late gestation feed...

  4. Postsurgical telecobalt radiotherapy of mammary carcinomas

    The first part of the study is a literature survey. The second part deals with patients and results of radiotherapy of the Klinik and Poliklinik fuer Radiologie der Universitaet Muenchen. The patients with mammary carcinomas, who were treated between 1960 and 1969 were classified according to the TNM classification or they were attributed to stage I or II or III. When the therapy was begun, the mean age of the patients was 55 years, 80% of the patients was between 40 and 60 years old, 45% of the patients were in stage I, 35% in stage II and almost 20% in stage III. (orig./MG)

  5. Mammary gland pathologies in the parturient buffalo

    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.

  6. ErbB2 enhances mammary tumorigenesis, oncogene-independent recurrence and metastasis in a model of IGF-IR-mediated mammary tumorigenesis

    Campbell Craig I

    2010-09-01

    Full Text Available Abstract Background The type I insulin-like growth factor receptor (IGF-IR and ErbB2 (Her-2 are receptor tyrosine kinases implicated in human breast cancer. Both proteins are currently the subject of targeted therapeutics that are used in the treatment of breast cancer or which are in clinical trials. The focus of this study was to utilize our inducible model of IGF-IR overexpression to explore the interaction of these two potent oncogenes. Results ErbB2 was overexpressed in our RM11A cell line, a murine tumor cell line that overexpresses human IGF-IR in an inducible manner. ErbB2 conferred an accelerated tumor onset and increased tumor incidence after injection of RM11A cells into the mammary glands of syngeneic wild type mice. This was associated with increased proliferation immediately after tumor cell colonization of the mammary gland; however, this effect was lost after tumor establishment. ErbB2 overexpression also impaired the regression of established RM11A tumors following IGF-IR downregulation and enhanced their metastatic potential. Conclusion This study has revealed that even in the presence of vast IGF-IR overexpression, a modest increase in ErbB2 can augment tumor establishment in vivo, mediate resistance to IGF-IR downregulation and facilitate metastasis. This supports the growing evidence suggesting a possible advantage of using IGF-IR and ErbB2-directed therapies concurrently in the treatment of breast cancer.

  7. Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation.

    Shuxian Jiang

    Full Text Available BACKGROUND: Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo. METHODOLOGY/PRINCIPAL FINDINGS: To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo. CONCLUSIONS/SIGNIFICANCE: Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate.

  8. Radiogenic neoplasia in thyroid and mammary clonogens

    The induction of cancer by ionizing radiation is a matter of great practical importance to the nuclear industry, to national defense, to radiological medicine and to the general public. It is increasingly apparent that carcinogenesis is one of the leading dose-limiting effects of radiation exposure (Co90). Quantitative information at the cellular level is essential to an understanding of the mechanisms of radiogenic neoplastic initiation and the stages of promotion and progression to overt neoplasia. We have developed two experimental models, the rat thyroid and rat mammary clonogen transplant systems, for the quantitative study of radiation carcinogenesis at the cellular level in vivo (C185). The most important steps taken or completed during the current grant year include: (a) demonstration of the high age-dependent radiosensitivity of prepubertal rat mammary clonogens to radiogenic damage which may influence their susceptibility to neoplastic initiation, and (b) demonstration of the feasibility of using a molecular test for clonogenicity in which Simple Sequence Repeats in the DNA serve as identifying signals of the genotypic origin of the cells. We have also (c) set up a large carcinogenesis experiment to test the effect of close intercellular contact in thyroid glands in situ on promotion-progression of radiogenically initiated clonogens, (d) achieved considerable further concentration of thyroid clonogens, and (e) begun to explore whether thyroid cells can be induced to give rise to three dimensional multicellular structures in culture in reconstituted basement membrane. These are discussed in this report

  9. Surface scanning: an application to mammary surgery

    Rigotti, Camilla; Ferrigno, Giancarlo; Aliverti, Andrea; Pedotti, Antonio

    1998-04-01

    The possibility of mathematically describing the body surface represents a useful tool for several medical sectors, such as prosthetics or plastic surgery, and could improve diagnosis and objective evaluation of deformities and the follow-up of progressive diseases. The approach presented is based on the acquisition of a surface scanned by a laser beam. The 3D coordinates of the spot generated on the surface by the laser beam are computed by an automatic image analyzer. Using at least two different views of the subject, the 3D coordinates are obtained by stereophotogrammetry. A software package for graphic representation and extraction of linear superficial and volumetric features from the acquired surface has been developed and some preliminary results with mammary reconstruction are presented. A good mammary reconstruction after mastectomy must achieve two results. First, the reconstruction should follow the patients' wishes and second, the reconstructed breast should be as similar as possible to the contralateral one. To achieve these goals, a knowledge of breast volume, area, and shape features are essential for the surgeon. In such a context, this system could be a valuable tool in improving breast reconstructive surgery.

  10. Progesterone induces adult mammary stem cell expansion.

    Joshi, Purna A; Jackson, Hartland W; Beristain, Alexander G; Di Grappa, Marco A; Mote, Patricia A; Clarke, Christine L; Stingl, John; Waterhouse, Paul D; Khokha, Rama

    2010-06-10

    Reproductive history is the strongest risk factor for breast cancer after age, genetics and breast density. Increased breast cancer risk is entwined with a greater number of ovarian hormone-dependent reproductive cycles, yet the basis for this predisposition is unknown. Mammary stem cells (MaSCs) are located within a specialized niche in the basal epithelial compartment that is under local and systemic regulation. The emerging role of MaSCs in cancer initiation warrants the study of ovarian hormones in MaSC homeostasis. Here we show that the MaSC pool increases 14-fold during maximal progesterone levels at the luteal dioestrus phase of the mouse. Stem-cell-enriched CD49fhi cells amplify at dioestrus, or with exogenous progesterone, demonstrating a key role for progesterone in propelling this expansion. In aged mice, CD49fhi cells display stasis upon cessation of the reproductive cycle. Progesterone drives a series of events where luminal cells probably provide Wnt4 and RANKL signals to basal cells which in turn respond by upregulating their cognate receptors, transcriptional targets and cell cycle markers. Our findings uncover a dynamic role for progesterone in activating adult MaSCs within the mammary stem cell niche during the reproductive cycle, where MaSCs are putative targets for cell transformation events leading to breast cancer. PMID:20445538

  11. Specialized membrane biogenesis in mammary epithelial cells

    The apical membrane of the mammary gland epithelial cell is highly differentiated and adapted to participate in the process of fat secretion. Certain of the apical membrane differentiation antigens are frequently expressed on membrane carcinoma cells, and knowledge of the normal mechanisms by which these antigens are regulated may have implications for a better understanding of tumor antigen expression. Because the apical membrane of the cell is lost during secretion, active membrane biosynthesis must accompany fat secretion, and the cell represents a good model for studying membrane biogenesis in polarized epithelial cells. Experiments have been carried out using primary cultures of cells established from mammary glands of late pregnant mice and also a mouse cell line, COMMA-1-D, that differentiates in an appropriate milieu. When fat globule membranes are purified from mouse milk and the protein composition analyzed by SDS-polyacrylamide gel electrophoresis, four major proteins are identifiable with molecular weights of 55, 67, 90, and 150 kDa. The 67-kDa component was identified as butyrophilin and the 150-kDa one as xanthine oxidase. In addition, a high molecular weight carbohydrate rich glycoprotein, PAS-O, is also present. 3 refs., 3 figs

  12. TCDD exposure disrupts mammary epithelial cell differentiation and function

    Collins, Loretta L.; Lew, Betina J.; Lawrence, B. Paige

    2009-01-01

    Mammary gland growth and differentiation during pregnancy is a developmental process that is sensitive to the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD is a widespread environmental contaminant and a potent ligand for the aryl hydrocarbon receptor (AhR). We demonstrate reduced β-casein protein induction in mouse mammary glands and in cultured SCp2 mammary epithelial cells following exposure to TCDD. SCp2 cells exposed to TCDD also show reduced cell clustering and less ...

  13. Mammary artery harvesting using the Da Vinci Si robotic system

    Leonardo Secchin Canale

    2014-03-01

    Full Text Available Internal mammary artery harvesting is an essential part of any coronary artery bypass operation. Totally endoscopic coronary artery bypass graft surgery has become reality in many centers as a safe and effective alternative to conventional surgery in selected patients. Internal mammary artery harvesting is the initial part of the procedure and should be performed equally safely if one wants to achieve excellence in patency rates for the bypass. We here describe the technique for mammary harvesting with the Da Vinci Si robotic system.

  14. A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

    Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm3. For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Using the first transgenic animal model to

  15. Control of ductal vs. alveolar differentiation of mammary clonogens and susceptibility to radiation-induced mammary cancer

    We have developed an in vitro-in vivo transplantation assay for measuring the concentration of clonogenic epithelial cells in cell suspensions of rat mammary tissue. Rat mammary clonogens from organoid cultures are capable of the same degree of PLDR as clonogens in vivo. The growth and differentiation of mammary clonogens to alveolar colonies or ductal colonies is regulated as follows: a) in the presence of E2 and high prolactin (Prl), cortisol induces mammary clonogens to proliferate and differentiate to form alveolar colonies which secrete milk and begin losing clonogenic potential, b) in cortisol deficient rats, Prl and E2 synergistically stimulate non-secretory ductal colonies, formation of which retain clonogenic potential, c) E2 without progesterone stimulates alveolar colony formation in the presence of cortical and high Prl, d) progesterone inhibits mammary clonogen differentiation to milk-producing cells and induces ductogenesis in a dose responsive fashion in the presence of E2, cortisol and high Prl. High prolactin levels coupled with glucocorticoid deficiency increases the susceptibility to mammary carcinogenesis following low dose radiation exposure by increasing the number of total mammary clonogens which are the presumptive target cells and by stimulating their proliferation after exposure. (author)

  16. Development of a mouse mammary tumor virus-negative mouse strain: a new system for the study of mammary carcinogenesis.

    Cohen, J C; Traina, V L; Breznik, T; Gardner, M.

    1982-01-01

    All inbred strains of mice transmit one or more copies of mouse mammary tumor virus (MMTV) DNA integrated as proviral sequences. This complicates efforts to define viral-induced mammary carcinogenesis. Here we report the use of surgical nonlethal splenectomy in tissue typing mice and the development of an MMTV-negative mouse strain. The MMTV-negative strain allows study of the involvement of non-MMTV genes in mammary carcinogenesis. In addition, it can be used as a sterile background into whi...

  17. Mammary remodelling and metabolic activity in dairy goats

    Safayi, Sina

    ) differences between PP and MP animals with respect to milk production and lactation persistency may be related to differences in mammary growth and remodelling also during lactation, 2) the factors responsible for interfering with mammary remodelling in continuous lactation throughout the dry period into the...... present thesis aimed to address the hypotheses that 1) differences between PP and MP animals with respect to milk production and lactation persistency may be related to differences in mammary growth and remodelling also during lactation, 2) the factors responsible for interfering with mammary remodelling...... be effectively renewed as one lactation comes to an end and prior to onset of the next lactation. Generally, the level of milk production and the changes in milk yield over the course of lactation depend on three main factors: 1) the number of MEC, which in turn is affected by the balance between the...

  18. Developmental biology: cell fate in the mammary gland

    Most breast cancers have their origin in the luminal epithelial cells of the mammary gland. Defining how a master regulator controls the development of this cell lineage could provide important hints about why this should be. ...

  19. Lessons Learned from Mouse Mammary Tumor Virus in Animal Models.

    Dudley, Jaquelin P; Golovkina, Tatyana V; Ross, Susan R

    2016-03-31

    Mouse mammary tumor virus (MMTV), which was discovered as a milk-transmitted, infectious, cancer-inducing agent in the 1930s, has been used as an animal model for the study of retroviral infection and transmission, antiviral immune responses, and breast cancer and lymphoma biology. The main target cells for MMTV infection in vivo are cells of the immune system and mammary epithelial cells. Although the host mounts an immune response to the virus, MMTV has evolved multiple means of evading this response. MMTV causes mammary tumors when the provirus integrates into the mammary epithelial and lymphoid cell genome during viral replication and thereby activates cellular oncogene expression. Thus, tumor induction is a by-product of the infection cycle. A number of important oncogenes have been discovered by carrying out MMTV integration site analysis, some of which may play a role in human breast cancer. PMID:27034391

  20. On How Mammary Gland Reprogramming Metalloproteinases Couple Form with Function

    Sloane, Bonnie F

    2012-01-01

    Metalloproteinases in extracellular proteolytic pathways are critical to mammary gland biology and tumorigenesis. However, intracellular and membrane proteases (e.g., caspases and cathepsins) may also play important roles.

  1. PPARδ activation acts cooperatively with 3-phosphoinositide-dependent protein kinase-1 to enhance mammary tumorigenesis.

    Claire B Pollock

    Full Text Available Peroxisome proliferator-activated receptorδ (PPARδ is a transcription factor that is associated with metabolic gene regulation and inflammation. It has been implicated in tumor promotion and in the regulation of 3-phosphoinositide-dependent kinase-1 (PDK1. PDK1 is a key regulator of the AGC protein kinase family, which includes the proto-oncogene AKT/PKB implicated in several malignancies, including breast cancer. To assess the role of PDK1 in mammary tumorigenesis and its interaction with PPARδ, transgenic mice were generated in which PDK1 was expressed in mammary epithelium under the control of the MMTV enhancer/promoter region. Transgene expression increased pT308AKT and pS9GSK3β, but did not alter phosphorylation of mTOR, 4EBP1, ribosomal protein S6 and PKCα. The transgenic mammary gland also expressed higher levels of PPARδ and a gene expression profile resembling wild-type mice maintained on a diet containing the PPARδ agonist, GW501516. Both wild-type and transgenic mice treated with GW501516 exhibited accelerated rates of tumor formation that were more pronounced in transgenic animals. GW501516 treatment was accompanied by a distinct metabolic gene expression and metabolomic signature that was not present in untreated animals. GW501516-treated transgenic mice expressed higher levels of fatty acid and phospholipid metabolites than treated wild-type mice, suggesting the involvement of PDK1 in enhancing PPARδ-driven energy metabolism. These results reveal that PPARδ activation elicits a distinct metabolic and metabolomic profile in tumors that is in part related to PDK1 and AKT signaling.

  2. Future accelerators (?)

    I describe the future accelerator facilities that are currently foreseen for electroweak scale physics, neutrino physics, and nuclear structure. I will explore the physics justification for these machines, and suggest how the case for future accelerators can be made

  3. Future accelerators (?)

    John Womersley

    2003-08-21

    I describe the future accelerator facilities that are currently foreseen for electroweak scale physics, neutrino physics, and nuclear structure. I will explore the physics justification for these machines, and suggest how the case for future accelerators can be made.

  4. Radiogenic neoplasia in thyroid and mammary clonogens

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process

  5. Chemoprevention of Radiation Induced Rat Mammary Neoplasms

    Huso, David L.

    1999-01-01

    Radiations encountered in space include protons and heavy ions such as iron as well as their secondaries. The relative biological effect (RBE) of these ions is not known, particularly at the doses and dose-rates expected for planetary missions. Neutrons, are not particularly relevant to space travel, but have been found experimentally to have an increase in their RBE with decreasing dose. If a similar trend of increasing RBE with decreasing dose is present for heavy ions and protons during irradiation in space, the small doses received during space travel could potentially have substantial carcinogenic risk. Clearly more investigation of the effects of heavy ions and protons is needed before accurate risk assessment for prolonged travel in space can be done. One means to mitigate the increased risk of cancer due to radiation exposure in space is by developing effective countermeasures that can reduce the incidence of tumor development. Tamoxifen has recently been shown to be an effective chemopreventive agent in both animal models and humans for the prevention of mammary tumors. Tamoxifen is a unique drug, with a highly specific mechanism of action affecting a specific radiation-sensitive population of epithelial cells in the mammary gland. In human studies, the annual incidence of a primary tumor in the contralateral breast of women with previous breast cancer is about 8 per 1000, making them an exceedingly high-risk group for the development of breast cancer. In this high risk group, treated with tamoxifen, daily, for 2 years, the incidence of a new primary tumor in the contralateral breast was approximately one third of that noted in the non-tamoxifen treatment group. Tamoxifen antagonizes the action of estrogen by competing for the nuclear receptor complex thereby altering the association of the receptor complex and nuclear binding sites. Its effects in reducing the development of breast cancer could be accomplished by controlling clinically undetectable

  6. Experimental studies on mammary tumors in rats

    The purpose of this study was to assess the effects of dietary fat components in radiation-induced rat mammary carcinogenesis, and the response of chemically- or radiation-induced rat mammary tumors (MT) to experimental radiotherapy. Female rats of F344 strain were fed, for 400 days after neutron irradiation, with a synthetic diet containing various fat components with different proportion. Transplanted MTs were tested for their response to radiotherapy in terms of their hormone dependency and antigenicity. An incidence rate of MT was significantly higher in rats given 20% corn oil than in those given 5% or 1% corn oil (61.5% vs 23.0% and 23.8%). In giving diet composed of different fat components with a constant rate of 20%, fish oil significantly inhibited the incidence of MT (16.7%) as compared with lard oil (77.0%) and corn oil (61.5%). In the case of corn oil, an MT incidence rate of 61.5% was reduced to 16.7% when the total caloric intake was decreased by 70%. No association was found between the MT incidence and serum levels of estrogen or prolactin in groups of different fat components. In rats transplanted with 7, 12-dimethylbenz(a)anthracene (DMBA), some of DMBA-induced MTs were spontaneously reduced, suggesting a high antigenicity. Other DMBA-induced MTs were rejected by syngeneic recipients upon cellular transplantation. A high antigenicity may be explained by tumor take and growth with a short latency upon transplantation into immunosuppressed syngeneic recipients. Ovarian hormone-dependent MTs tended to have a higher radiosensitivity than hormone-independent autonomous MTs. DMBA-induced MTs began to reduce 10 days and were completely destroyed 30 days after irradiation, irrespective of whether they were directly exposed to or shielded from neutron. This abscopal effect can be explained by immunological reaction of the host. (Namekawa, K) 87 refs

  7. Equine estrogen-induced mammary tumors in rats

    Okamoto, Yoshinori; Liu, Xiaoping; Suzuki, Naomi; OKAMOTO, KANAKO; Kim, Hyo Jeong; Santosh Laxmi, Y. R.; Sayama, Kazutoshi; Shibutani, Shinya

    2010-01-01

    Long-term hormone replacement therapy is associated with an increased risk of breast, ovarian and endometrial cancers in women. Equine estrogens are a principal component of hormone replacement therapy; however, their tumorigenic potential toward mammary tissue and reproductive organs has not been extensively explored. A pellet containing equilin was inserted under the skin of female ACI rats and the development of mammary tumors was monitored. Histological examination revealed premalignant l...

  8. The First Turkish Family with Ulnar Mammary Syndrome

    Karaarslan, Neşe; Tükel, Turgut; Kayserili, Hülya; Apak, Memnune Yüksel

    1998-01-01

    Ulnar mammary syndrome UMS is characterized by ulnar limb deficiencies or duplications apocrine mammary gland hypoplasia and or dysfunction abnormal dentition and genital anomalies The syndrome is inherited in an autosomal dominant manner with variable expression and different penetrance It was first described in 1975 by Mc Kusick citing a personal communication with Schinzel 1973 Here we describe a family with 9 affected individuals in 3 generations showing variable expressivity of UMS Key w...

  9. Condition of mammary glands in adolescent girls in Saratov region

    Kunina A.V.; Eyberman A.S.; Chernenkov Yu.V.; Gumenyuk O.I.; Kunina S.V.

    2011-01-01

    The study was undertaken to estimate the condition of mammary glands in adolescent girls. Material and methods. The study included 867 girls (aged 12-18). The questioning, total clinical examination, hormonal analysis and ultrasound examination were conducted. Results. The investigation shows that girls had breast dysmorphies (macromastia, hypoplasia, striae, asymmetry etc.). The dysplasia of mammary glands was diagnosed in 26% patients with menstrual disorders, thyroid diseases, mastalgia an...

  10. Human Mammary Tumor Virus (HMTV) sequences in human milk

    Nartey, Teiko; Moran, Heberth; Marin, Tania; Arcaro, Kathleen F; Anderton, Douglas L; Etkind, Polly; Holland, James F; Melana, Stella M; Pogo, Beatriz G-T

    2014-01-01

    Background Retroviral sequences 90-95% homologous to the mouse mammary tumor virus (MMTV) were present in 38% of the breast cancers studied from American women and were not detectable in non-tumor breast tissue from the same patient. The entire proviral structure was described and viral particles were isolated from primary cultures of human breast cancer. This virus was designated as human mammary tumor virus (HMTV). Hormone response elements present in the HMTV Long-Terminal-Repeat (LTR) sug...

  11. Immunohistochemical detection of estrogen receptors in canine mammary tumors

    Elena Atanaskova Petrov; Ivica Gjurovski; Trpe Ristoski; Goran Nikolovski; Pandorce Trenkoska; Plamen Trojacanec; Ksenija Ilievska; Toni Dovenski; Gordana Petrushevska

    2016-01-01

    Mammary tumors are among the most common neoplasms in intact female dogs.They have a complex morphology, usually affecting middle age and older bitches. Almost 50% of the mammary tumors in dogs are malignant neoplasms. Prognosis is based on several factors: stage, age, tumor size, metastasis, histopathology, ovariectomy status and hormone-receptor activity. Immunohistochemical (IHC) measurement has become increasingly an important diagnostic and prognostic parameter, with the development of m...

  12. Internal mammary lymph node biopsy guided by computed tomography

    Irving, Henry C; Hardy, Graham J.

    1982-01-01

    Internal mammary lymph node enlargement may be demonstrated using computed tomography (CT), and a confirmatory tissue diagnosis of metastatic involvement may be obtained using fine needle aspiration biopsy with needle tip placement guided by the CT scanner. A case history is described to illustrate how a patient presented 9 years after mastectomy with an internal mammary lymph node metastasis and how cytopathological diagnosis of this metastasis was achieved by CT guided biopsy.

  13. Laminin Mediates Tissue-specific Gene Expression in Mammary Epithelia

    Streuli, Charles H

    2011-01-01

    Tissue-specific gene expression in mammary epithelium is dependent on the extracellular matrix as well as hormones. There is good evidence that the basement membrane provides signals for regulating beta-casein expression, and that integrins are involved in this process. Here, we demonstrate that in the presence of lactogenic hormones, laminin can direct expression of the beta-casein gene. Mouse mammary epithelial cells plated on gels of native laminin or laminin-entactin undergo functional di...

  14. Accelerating Value Creation with Accelerators

    Jonsson, Eythor Ivar

    2015-01-01

    accelerator programs. Microsoft runs accelerators in seven different countries. Accelerators have grown out of the infancy stage and are now an accepted approach to develop new ventures based on cutting-edge technology like the internet of things, mobile technology, big data and virtual reality. It is also......Accelerators can help to accelerate value creation. Accelerators are short-term programs that have the objective of creating innovative and fast growing ventures. They have gained attraction as larger corporations like Microsoft, Barclays bank and Nordea bank have initiated and sponsored...

  15. Wnt4 is not sufficient to induce lobuloalveolar mammary development

    Pelegri Francisco

    2009-10-01

    Full Text Available Abstract Background Brisken et al (2000 showed that Wnt4 null mammary glands were deficient in early lobuloalveolar mammary outgrowth during pregnancy, and implicated Wnt4 as an effector for the progesterone-induced mammary growth program. Though ectopic Wnt1 signaling is known to be mitogenic and oncogenic, no endogenously expressed Wnt ligands have ever been directly implicated in mammary growth and morphogenesis. Therefore, we generated conditional transgenic mice to test whether Wnt4 can stimulate mammary epithelial cell growth. Results We found that despite pregnancy-associated expression levels of Wnt4, mammary glands did not display the side-branching typical of early pregnancy. Control experiments designed to test the Wnt4 construct in zebrafish reproduced other studies that demonstrated Wnt4-specific phenotypes distinct from Wnt1-induced phenotypes. Indeed, using qPCR-based array analyses, we found that a specific transcriptional target of Wnt4, namely Wnt16, was induced in Wnt4-expressing transgenic glands, to levels equivalent to that of early pregnant glands. Conclusion Taken together, we propose that Wnt4 is necessary, but not sufficient, to induce side-branch development.

  16. Effect of ovariohysterectomy in bitches with mammary neoplasms.

    Morris, J S; Dobson, J M; Bostock, D E; O'Farrell, E

    1998-06-13

    Ninety bitches with mammary tumours were studied for two years after the surgical removal of the primary tumour(s). Twenty-nine of the bitches had been spayed before the development of the mammary tumour, 22 were spayed when the tumours were removed and 39 were left entire. Fifty-eight of the bitches (64 per cent) had benign tumours and, of these, 15 (26 per cent) developed a new mammary tumour within two years, irrespective of whether the bitch was spayed. The other 32 bitches had malignant tumours which were grouped into 'invasive' and 'well defined' carcinomas. Sixty-three per cent of the spayed bitches and 57 per cent of the entire bitches, with invasive carcinoma were dead within two years of surgery as a result of their mammary tumours. For those with well defined carcinomas the tumour-related death rates were 18 per cent and 33 per cent respectively for the spayed and entire bitches. These findings suggest that ovariohysterectomy when mammary tumours are removed does not have a significant effect on the progression of malignant disease, and that about one in four bitches with a benign mammary tumour is likely to develop a further tumour in another gland. PMID:9670443

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

    2013-01-01

    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...

  18. Distinct luminal type mammary carcinomas arise from orthotopic Trp53 null mammary transplantation of juvenile versus adult mice

    Nguyen, David H.; Ouyang, Haoxu; Mao, Jian-Hua; Hlatky, Lynn; Barcellos-Hoff, Mary Helen

    2014-01-01

    Age and physiological status, like menopause, are risk factors for breast cancer. Less clear is what factors influence the diversity of breast cancer. In this study, we investigated the effect of host age on the distribution of tumor subtypes in mouse mammary chimera consisting of wild-type hosts and Trp53 nullizygous epithelium, which undergoes a high rate of neoplastic transformation. Wild-type mammary glands cleared of endogenous epithelium at 3 weeks of age were subsequently implanted dur...

  19. Estrogen receptor isoforms and progestin hormone dependence in a mouse mammary tumor model.

    Actis, A M; Caruso, S P; Levin, E

    1994-09-01

    The close interaction between receptors and other transcription factors suggests that their corresponding transducing signals can trigger functional and structural changes in other related molecules. The effect of a progestinic agent, medroxyprogesterone acetate (MPA), on some of the estrogen-receptor (ER) parameters was studied in 2 murine mammary tumor sublines with different progestin hormone dependence for their respective growth. The relative binding affinity of estradiol and tamoxifen for the ER, the receptor content and the ER isoforms studied by HPLC were determined in the hormone-autonomous (HA) and the hormone-dependent (HD) tumor sublines. In the HA subline administration of MPA did not modify the tumor growth rate, whereas this was accelerated in the HD subline. The ER content was clearly increased in the HD tumor subline, but not in the HA subline, compared with the untreated controls. In contrast, the E2 and tamoxifen relative binding affinity for the ER and the isoform profiles were affected by MPA treatment in the HA, but not in the HD tumor subline. The functional change (decrease in relative binding affinity) can be attributed to the appearance of a lower-molecular-size ER isoform under the progestinic treatment. Modifications in one receptor molecule by the action of ligands corresponding to another type of receptor show the interconection between transcription factors and the necessity of broadening conventional concepts regarding hormone dependence in mammary tumorigenesis. PMID:8077051

  20. The expression of oncogenes on the radiation-induced apoptosis in SCK mammary adenocarcinoma cell line

    The expression of p53, p21/WAF/CIP, Bcl-2, and Bax underlying the radiation-induced apoptosis in different pH environments using SCK mammary adenocarcinoma cell line was investigated. Mammary adenocarcinoma cells of A/J mice (SCK cells) in exponential growth phase were irradiated with a linear accelerator at room temperature. The cells were irradiated with 12 Gy and one hour later, the media was replaced with fresh media at a different pHs. After incubation at 37 .deg. for 0-48 h, the extent of apoptosis was determined using agarose gel electrophoresis and flow cytometry. The progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. Western blot analysis was used to monitor p53, P21/WAF/CIP, BcI-2, and Bax protein levels. The induction of apoptosis by irradiation in pH 6.6 medium was markedly less than that in pH 7.5 medium. The radiation-induced G2/M arrest in pH 6.6 medium lasted markedly longer than that in pH 7.5 medium. Considerable amounts of p53 and p21 proteins already existed at pH 7.5 and increased the level of p53 and p21 significantly after 12 Gy X-irradiation. An incubation at pH6.6 after 12 Gy X-irradiation did not change the level of p53 and p21 protein levels significantly. BcI-2 proteins were not significantly affected by radiation and showed no correlation with cell susceptibility to radiation-induced apoptosis in different pHs. An exposure to 12 Gy of X-rays increased the level of Bax protein at pH 7.5 but at pH 6.6, it was slight. The molecular mechanism underlying radiation-induced apoptosis in different pH environments using SCK mammary adenocarcinoma cell line was dependent of the expression p53 and p21/WAF/CIP proteins. We may propose following hypothesis that an acidic stress augments the radiation-induced G2/M arrest, which inhibiting the irradiated cells undergo post-mitotic apoptosis. The effects of environmental acidity on anti-apoptotic and pro-apoptotic function of BcI-2

  1. Contribution of MIBI 99mTc mammary scintigraphy in mammary cancer detection

    Recent publications indicate the interest in 99mTc - SESTA-MIBI in diagnosing mammary cancers. The goal of this paper was to study the feasibility of this method and define its place relative to the classical tripod: mammography, echography, cyto-puncture. The mammary scintigraphy is achieved, in condition ventral-decubitus at 10 minutes after the injection of 20 mCi of SESTA-MIBI, in 100 patients for which a surgery decision was made. Ten minute incidences from the left, right and front sides were achieved. A visual score ranging from G1 to G4 was established: G1 - no anomalous fixation; G2 - slight fixation of irregular shape; G3 - moderate well-defined fixation; G4 - intense circular fixation. The final diagnosis is given by histology. Results with the score ranging from G1 to G4 for five diagnosis types are given. By considering G3 and G4 as positive to biopsy the sensitivity found was 91.2%; the specificity, 62.8%; the positive predicting value, 76.4% and the VPN, 84.4%. Five falsely negative cancers correspond to micro-calcification sub-centimeter lesions. In conclusion, the contribution of the mammary scintigraphy consists in identification of positive MIBI lesions having a uncertain and/or ensuring ensuring and multi-focal lesions for the cases in which the tripod indicate a single lesion. Making evident these multi-focal lesions allows establishing a surgical operation scheme which will guide an enlarged extirpation

  2. Proteotypic classification of spontaneous and transgenic mammary neoplasms

    Mammary tumors in mice are categorized by using morphologic and architectural criteria. Immunolabeling for terminal differentiation markers was compared among a variety of mouse mammary neoplasms because expression of terminal differentiation markers, and especially of keratins, provides important information on the origin of neoplastic cells and their degree of differentiation. Expression patterns for terminal differentiation markers were used to characterize tumor types and to study tumor progression in transgenic mouse models of mammary neoplasia (mice overexpressing Neu (Erbb2), Hras, Myc, Notch4, SV40-TAg, Tgfa, and Wnt1), in spontaneous mammary carcinomas, and in mammary neoplasms associated with infection by the mouse mammary tumor virus (MMTV). On the basis of the expression of terminal differentiation markers, three types of neoplasm were identified: first, simple carcinomas composed exclusively of cells with a luminal phenotype are characteristic of neoplasms arising in mice transgenic for Neu, Hras, Myc, Notch4, and SV40-TAg; second, 'complex carcinomas' displaying luminal and myoepithelial differentiation are characteristic of type P tumors arising in mice transgenic for Wnt1, neoplasms arising in mice infected by the MMTV, and spontaneous adenosquamous carcinomas; and third, 'carcinomas with epithelial to mesenchymal transition (EMT)' are a characteristic feature of tumor progression in Hras-, Myc-, and SV40-TAg-induced mammary neoplasms and PL/J and SJL/J mouse strains, and display de novo expression of myoepithelial and mesenchymal cell markers. In sharp contrast, EMT was not detected in papillary adenocarcinomas arising in BALB/cJ mice, spontaneous adenoacanthomas, neoplasms associated with MMTV-infection, or in neoplasms arising in mice transgenic for Neu and Wnt1. Immunohistochemical profiles of complex neoplasms are consistent with a stem cell origin, whereas simple carcinomas might originate from a cell committed to the

  3. Lymphatic vessels assessment in feline mammary tumours

    Diracca Laura

    2007-01-01

    Full Text Available Abstract Background The lymphatic vessels play a crucial role in a variety of human cancers since tumour cell lymphatic invasion significantly influences prognosis. It is not known if pre-existing lymphatics are enough for tumour dissemination or de novo development is necessary. VEGFR-3 is an angiogenetic mediator for both lymphatic and blood vessels during embryonic development, and only for lymphatics after birth. VEGF is a mediator of both vasculogenesis and angiogenesis, regulates the growth of lymphatics in various experimental models, and is produced in many solid tumours. CD44 mediates hyaluronic acid (HA-dependent cell adhesion: besides promoting invasion, this interaction also supports neoangiogenesis that indirectly stimulates tumour cell proliferation. The expression of VEGF-C (Vascular Endothelial Growth Factor – C, its receptor VEGFR-3 and CD44, were studied on feline mammary samples to assess the importance of lymphangiogenesis and lymphangiotrophism in neoplasia. Methods Samples were taken from six normal mammary glands (NMG, ten benign (BT and 32 malignant (MT tumours. Immunohistochemical laminin/VEGFR-3 double stain, VEGF-C and CD44 stains were applied to 4 μm-thick sections, and their expression evaluated in intratumoral/extratumoral and intramammary/extramammary fields. Results All groups revealed a higher number of lymphatics in the extratumoral/extramammary areas. VEGF-C expression in the epithelium paralleled the number of positive vessels in the NMG, BT and MT, whereas VEGF-C higher expression was noted in the intratumoral fields only in infiltrating MT. CD44 score was lower in extratumoral than intratumoral fields in tumours and showed a significant increase in extramammary/extratumoral fields from NMG to MT. Pearson test showed a significant and inversely proportional correlation between CD44 expression and the number of lymphatic vessels with VEGFR-3 in malignant infiltrating tumours. Conclusion The number of both

  4. Isolation and characterization of proteins of the mouse mammary tumour virus

    A vaccination procedure was developed to mouse mammary tumor virus (MuMTV) induced mouse mammary tumorigenesis. The structural proteins of MuMTV were purified so that their immunogenic qualities were retained. Radioimmunoassays were developed for the proteins. (Auth.)

  5. Laser accelerator

    Vigil, Ricardo

    2014-01-01

    Approved for public release; distribution is unlimited In 1979,W. B. Colson and S. K. Ride proposed a new kind of electron accelerator using a uniform magnetic field in combination with a circularly-polarized laser field. A key concept is to couple the oscillating electric field to the electron’s motion so that acceleration is sustained. This dissertation investigates the performance of the proposed laser accelerator using modern high powered lasers and mag-netic fields that are significan...

  6. Amino acids and mammary gland development: nutritional implications for milk production and neonatal growth

    Rezaei, Reza; Wu, Zhenlong; Hou, Yongqing; Fuller W Bazer; Wu, Guoyao

    2016-01-01

    Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural development of the mammary gland occurs during fetal growth, prepubertal and post-pubertal periods, pregnancy, and lactation under the control of various hormones (particularly estrogen, growth hormone, insulin-like growth factor-I, progesterone, placental lactogen, and prolactin) in a ...

  7. Nuclear proteins from lactating mammary glands bind to the promoter of a milk protein gene.

    LUBON, H.; Hennighausen, L

    1987-01-01

    The gene for the whey acidic protein (WAP) is expressed specifically in the lactating mammary glands of rodents. We present evidence that nuclear proteins from mammary epithelial cells form a multiple nucleoprotein complex with the WAP gene promoter/upstream region. As monitored by mobility shifts, nuclear proteins from lactating mammary glands and from the mammary cell line MCF-7 form four high affinity complexes with a fragment spanning the region between nucleotides -175 and -88. Nuclear p...

  8. Cytokeratin expression during mouse embryonic and early postnatal mammary gland development

    Sun, Peng; Yuan, Yuanyang; Li, Aihua; Li, Boan; Dai, Xing

    2009-01-01

    Cytokeratins are intermediate filament proteins found in most epithelial cells including the mammary epithelium. Specific cytokeratin expression has been found to mark different epithelial cell lineages and also to associate with putative mammary stem/progenitor cells. However, a comparative analysis of the expression of cytokaratins during embryonic and postnatal mammary development is currently lacking. Moreover, it is not clear whether the different classes of putative mammary stem/progeni...

  9. A temporal requirement for Hippo signaling in mammary gland differentiation, growth, and tumorigenesis

    Chen, Qian; Zhang, Nailing; Gray, Ryan S.; Li, Huili; Ewald, Andrew J.; Zahnow, Cynthia A.; Pan, Duojia

    2014-01-01

    In this study, Chen et al. discover that the Hippo pathway is functionally dispensable in virgin mammary glands but specifically required during pregnancy. YAP hyperactivation in mammary epithelia leads to defects in terminal differentiation. Loss of YAP causes no obvious defects in virgin mammary glands but potently suppresses oncogene-induced mammary tumors. This selective requirement for YAP in oncogenic growth suggests YAP inhibitors as targeted therapies against breast cancers.

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

    KINOSHITA, YUICHI; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; SHIKATA, NOBUAKI; Tsubura, Airo

    2014-01-01

    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 whol...

  11. Differential Roles of ERα and ERβ in Normal and Neoplastic Development in the Mouse Mammary Gland

    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...

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

    Vicki Plaks; Audrey Brenot; Devon A. Lawson; Linnemann, Jelena R.; Eline C. Van Kappel; Karren C. Wong; Frederic de Sauvage; Ophir D. Klein; Zena Werb

    2013-01-01

    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 regenerati...

  13. Functional Characterization of Stem Cell Activity in the Mouse Mammary Gland

    Bruno, Robert D.; Smith, Gilbert H.

    2011-01-01

    Any portion of the mouse mammary gland is capable of recapitulating a clonally derived complete and functional mammary tree upon transplantation into an epithelial divested mammary fat-pad of a recipient host. As such, it is an ideal model tissue for the study somatic stem cell function. This review will outline what is known regarding the function of stem/progenitor cells in the mouse mammary gland, including how progenitor populations can be functionally defined, the evidence for and potent...

  14. Mammary number and litter size in Rodentia: The “one-half rule”

    Gilbert, Avery Nelson

    1986-01-01

    Litter size and mammary number in the mammalian order Rodentia show a significant positive correlation. Mean litter size is typically one-half the number of available mammaries, while maximum litter size approximates mammary number. Similar relationships are found in the families Muridae, Cricetidae, and Sciuridae. The relationship of litter size to mammary number is significantly different between the arboreal and terrestrial squirrels, and between the hystricomorph and nonhystricomorph rode...

  15. Heat shock protein expression in canine malignant mammary tumours

    Sarli Giuseppe

    2006-06-01

    Full Text Available Abstract Background Abnormal levels of Heat Shock Proteins (HSPs have been observed in many human neoplasms including breast cancer and it has been demonstrated that they have both prognostic and therapeutic implications. In this study, we evaluated immunohistochemical expression of HSPs in normal and neoplastic canine mammary glands and confronted these results with overall survival (OS, in order to understand the role of HSPs in carcinogenesis and to establish their potential prognostic and/or therapeutic value. Methods Immunohistochemical expression of Hsp27, Hsp72, Hsp73 and Hsp90 was evaluated in 3 normal canine mammary glands and 30 malignant mammary tumours (10 in situ carcinomas, 10 invasive carcinomas limited to local structures without identifiable invasion of blood or lymphatic vessels, 10 carcinomas with invasion of blood or lymphatic vessels and/or metastases to regional lymph nodes. A semi-quantitative method was used for the analysis of the results. Results Widespread constitutive expression of Hsp73 and Hsp90 was detected in normal tissue, Hsp72 appeared to be focally distributed and Hsp27 showed a negative to rare weak immunostaining. In mammary tumours, a significant increase in Hsp27 (P Conclusion These results suggest that Hsp27, Hsp72 and Hsp90 are involved in canine mammary gland carcinogenesis. In addition, Hsp27 appears to be implicated in tumour invasiveness and its high immunodetection in invasive tumours is indicative of a poorer clinical outcome.

  16. Thyroid hormone requirement for retinoic acid induction of mouse mammary tumor virus expression.

    Bolander, F F; Blackstone, M E

    1990-01-01

    In normal mouse mammary epithelium, insulin, cortisol, and prolactin are absolute requirements for mouse mammary tumor virus expression. Retinoic acid further increased mouse mammary tumor virus expression two- to threefold but only when triiodothyronine was also present; neither retinoic acid nor triiodothyronine alone had any effect.

  17. File list: ALL.Brs.10.AllAg.Mammary_cells [Chip-atlas[Archive

    Full Text Available ALL.Brs.10.AllAg.Mammary_cells mm9 All antigens Breast Mammary cells SRX187511,SRX1...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.10.AllAg.Mammary_cells.bed ...

  18. File list: ALL.Brs.05.AllAg.Mammary_cells [Chip-atlas[Archive

    Full Text Available ALL.Brs.05.AllAg.Mammary_cells mm9 All antigens Breast Mammary cells SRX187511,SRX1...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.05.AllAg.Mammary_cells.bed ...

  19. File list: Oth.Brs.50.AllAg.Mammary_cells [Chip-atlas[Archive

    Full Text Available Oth.Brs.50.AllAg.Mammary_cells mm9 TFs and others Breast Mammary cells SRX187508,SR...X187509,SRX187514,SRX403482,SRX852562,SRX187513,SRX403483,SRX852565,SRX852563,SRX852564 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.50.AllAg.Mammary_cells.bed ...

  20. File list: Pol.Brs.50.AllAg.Mammary_cells [Chip-atlas[Archive

    Full Text Available Pol.Brs.50.AllAg.Mammary_cells mm9 RNA polymerase Breast Mammary cells SRX852566,SR...X187510,SRX852567,SRX187515 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.50.AllAg.Mammary_cells.bed ...

  1. File list: Pol.Brs.05.AllAg.Mammary_cells [Chip-atlas[Archive

    Full Text Available Pol.Brs.05.AllAg.Mammary_cells mm9 RNA polymerase Breast Mammary cells SRX187510,SR...X187515,SRX852567,SRX852566 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.05.AllAg.Mammary_cells.bed ...

  2. File list: Oth.Brs.05.AllAg.Mammary_cells [Chip-atlas[Archive

    Full Text Available Oth.Brs.05.AllAg.Mammary_cells mm9 TFs and others Breast Mammary cells SRX187508,SR...X403482,SRX852565,SRX187509,SRX403483,SRX187514,SRX852563,SRX852562,SRX187513,SRX852564 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.05.AllAg.Mammary_cells.bed ...

  3. File list: InP.Brs.20.AllAg.Mammary_cells [Chip-atlas[Archive

    Full Text Available InP.Brs.20.AllAg.Mammary_cells mm9 Input control Breast Mammary cells SRX403481,SRX...187517,SRX187512,SRX403484 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Brs.20.AllAg.Mammary_cells.bed ...

  4. Mammary carcinogenesis in rats: basic facts and recent results in Brookhaven

    Shellabarger, C.J.; Stone, J.P.; Holtzman, s.

    1982-01-01

    Some research results from experiments investigating neutron-induced mammary carcinogenesis in rats are presented. The additive effects of neutrons and 3-methylcholanthrene on mammary adenocarcinoma were determined. Synergism between diethylstilbestrol and neutrons was likewise studied. Differences in mammary neoplastic response between strains of laboratory rats was also investigated. (ACR)

  5. Mammary carcinogenesis in rats: basic facts and recent results in Brookhaven

    Some research results from experiments investigating neutron-induced mammary carcinogenesis in rats are presented. The additive effects of neutrons and 3-methylcholanthrene on mammary adenocarcinoma were determined. Synergism between diethylstilbestrol and neutrons was likewise studied. Differences in mammary neoplastic response between strains of laboratory rats was also investigated

  6. File list: His.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available His.Brs.05.AllAg.Mammary_stem_cells mm9 Histone Breast Mammary stem cells SRX213393...,SRX213410,SRX213404,SRX185809,SRX185869,SRX213407 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.05.AllAg.Mammary_stem_cells.bed ...

  7. File list: ALL.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available ALL.Brs.10.AllAg.Mammary_stem_cells mm9 All antigens Breast Mammary stem cells SRX1...91028,SRX188640,SRX213393,SRX213410,SRX213404,SRX213407,SRX185869,SRX185809,SRX185841 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.10.AllAg.Mammary_stem_cells.bed ...

  8. File list: His.Brs.50.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available His.Brs.50.AllAg.Mammary_stem_cells mm9 Histone Breast Mammary stem cells SRX213393...,SRX185869,SRX185809,SRX213410,SRX213404,SRX213407 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.50.AllAg.Mammary_stem_cells.bed ...

  9. File list: Oth.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available Oth.Brs.05.AllAg.Mammary_stem_cells mm9 TFs and others Breast Mammary stem cells ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.05.AllAg.Mammary_stem_cells.bed ...

  10. File list: Oth.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available Oth.Brs.10.AllAg.Mammary_stem_cells mm9 TFs and others Breast Mammary stem cells ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.10.AllAg.Mammary_stem_cells.bed ...

  11. File list: ALL.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available ALL.Brs.05.AllAg.Mammary_stem_cells mm9 All antigens Breast Mammary stem cells SRX1...85841,SRX188640,SRX191028,SRX213393,SRX213410,SRX213404,SRX185809,SRX185869,SRX213407 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.05.AllAg.Mammary_stem_cells.bed ...

  12. File list: Pol.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available Pol.Brs.10.AllAg.Mammary_stem_cells mm9 RNA polymerase Breast Mammary stem cells ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.10.AllAg.Mammary_stem_cells.bed ...

  13. File list: Unc.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available Unc.Brs.10.AllAg.Mammary_stem_cells mm9 Unclassified Breast Mammary stem cells http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.10.AllAg.Mammary_stem_cells.bed ...

  14. File list: Unc.Brs.50.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available Unc.Brs.50.AllAg.Mammary_stem_cells mm9 Unclassified Breast Mammary stem cells http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.50.AllAg.Mammary_stem_cells.bed ...

  15. File list: Unc.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available Unc.Brs.05.AllAg.Mammary_stem_cells mm9 Unclassified Breast Mammary stem cells http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.05.AllAg.Mammary_stem_cells.bed ...

  16. File list: His.Brs.20.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available His.Brs.20.AllAg.Mammary_stem_cells mm9 Histone Breast Mammary stem cells SRX213393...,SRX213410,SRX185869,SRX185809,SRX213404,SRX213407 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.20.AllAg.Mammary_stem_cells.bed ...

  17. File list: DNS.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available DNS.Brs.10.AllAg.Mammary_stem_cells mm9 DNase-seq Breast Mammary stem cells SRX1910...28,SRX188640 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Brs.10.AllAg.Mammary_stem_cells.bed ...

  18. File list: Pol.Brs.50.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available Pol.Brs.50.AllAg.Mammary_stem_cells mm9 RNA polymerase Breast Mammary stem cells ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.50.AllAg.Mammary_stem_cells.bed ...

  19. File list: Pol.Brs.50.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available Pol.Brs.50.AllAg.Mammary_glands mm9 RNA polymerase Breast Mammary glands SRX1078976...,SRX1184165,SRX1078977,SRX1078989,SRX1078990 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.50.AllAg.Mammary_glands.bed ...

  20. File list: His.Brs.50.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available His.Brs.50.AllAg.Mammary_glands mm9 Histone Breast Mammary glands SRX396744,SRX1184...,SRX031072,SRX031071,SRX031211 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.50.AllAg.Mammary_glands.bed ...

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

    Full Text Available His.Brs.10.AllAg.Mammary_glands mm9 Histone Breast Mammary glands SRX396744,SRX1184...,ERX200437,ERX200405,ERX200401 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.10.AllAg.Mammary_glands.bed ...

  2. File list: InP.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available InP.Brs.05.AllAg.Mammary_glands mm9 Input control Breast Mammary glands SRX213417,S...00420,ERX200416,ERX200438,SRX1078980,ERX200398,ERX200402 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Brs.05.AllAg.Mammary_glands.bed ...

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

    Full Text Available Oth.Brs.50.AllAg.Mammary_glands mm9 TFs and others Breast Mammary glands SRX209679,...200399 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.50.AllAg.Mammary_glands.bed ...

  4. File list: Unc.Brs.50.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available Unc.Brs.50.AllAg.Mammary_glands mm9 Unclassified Breast Mammary glands SRX216177 ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.50.AllAg.Mammary_glands.bed ...

  5. File list: Pol.Brs.20.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available Pol.Brs.20.AllAg.Mammary_glands mm9 RNA polymerase Breast Mammary glands SRX1184165...,SRX1078976,SRX1078977,SRX1078989,SRX1078990 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.20.AllAg.Mammary_glands.bed ...

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

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

    Full Text Available Unc.Brs.20.AllAg.Mammary_glands mm9 Unclassified Breast Mammary glands SRX216177 ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.20.AllAg.Mammary_glands.bed ...

  8. File list: InP.Brs.20.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available InP.Brs.20.AllAg.Mammary_glands mm9 Input control Breast Mammary glands SRX213420,S...0406,ERX200402,SRX1078980,SRX396747,SRX396745,SRX1078982 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Brs.20.AllAg.Mammary_glands.bed ...

  9. File list: InP.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available InP.Brs.10.AllAg.Mammary_glands mm9 Input control Breast Mammary glands SRX213411,E...200398,ERX200420,ERX200438,ERX200429,ERX200402,SRX396747 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Brs.10.AllAg.Mammary_glands.bed ...

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

    Full Text Available Oth.Brs.10.AllAg.Mammary_glands mm9 TFs and others Breast Mammary glands SRX209678,...200399 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.10.AllAg.Mammary_glands.bed ...

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

    Full Text Available Pol.Brs.05.AllAg.Mammary_glands mm9 RNA polymerase Breast Mammary glands SRX1078977...,SRX1184165,SRX1078989,SRX1078976,SRX1078990 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.05.AllAg.Mammary_glands.bed ...

  12. File list: ALL.Brs.50.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available ALL.Brs.50.AllAg.Mammary_glands mm9 All antigens Breast Mammary glands SRX396744,SR...31072,SRX031071,SRX031211,SRX216177,SRX1078980,SRX396747,SRX396745,SRX1078982 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.50.AllAg.Mammary_glands.bed ...

  13. File list: His.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available His.Brs.05.AllAg.Mammary_glands mm9 Histone Breast Mammary glands ERX200400,SRX2134...,ERX200419,ERX200401,ERX200405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.05.AllAg.Mammary_glands.bed ...

  14. File list: Oth.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available Oth.Brs.05.AllAg.Mammary_glands mm9 TFs and others Breast Mammary glands ERX200430,...200399 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.05.AllAg.Mammary_glands.bed ...

  15. File list: Unc.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available Unc.Brs.10.AllAg.Mammary_glands mm9 Unclassified Breast Mammary glands SRX216177 ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.10.AllAg.Mammary_glands.bed ...

  16. File list: ALL.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available ALL.Brs.05.AllAg.Mammary_glands mm9 All antigens Breast Mammary glands ERX200400,ER...216177,ERX200416,ERX200438,SRX1078980,ERX200398,ERX200402,ERX200399,ERX200405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.05.AllAg.Mammary_glands.bed ...

  17. File list: ALL.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available ALL.Brs.10.AllAg.Mammary_glands mm9 All antigens Breast Mammary glands SRX213411,SR...X200417,ERX200426,ERX200435,SRX396747,ERX200437,ERX200399,ERX200405,ERX200401 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.10.AllAg.Mammary_glands.bed ...

  18. File list: Oth.Brs.20.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available Oth.Brs.20.AllAg.Mammary_glands mm9 TFs and others Breast Mammary glands SRX209678,...200399 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.20.AllAg.Mammary_glands.bed ...

  19. File list: ALL.Brs.20.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available ALL.Brs.20.AllAg.Mammary_glands mm9 All antigens Breast Mammary glands SRX209678,SR...31209,SRX031208,SRX031071,SRX216177,SRX1078980,SRX396747,SRX396745,SRX1078982 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.20.AllAg.Mammary_glands.bed ...

  20. File list: Pol.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

    Full Text Available Pol.Brs.10.AllAg.Mammary_glands mm9 RNA polymerase Breast Mammary glands SRX1184165...,SRX1078977,SRX1078976,SRX1078989,SRX1078990 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.10.AllAg.Mammary_glands.bed ...

  1. File list: ALL.Brs.50.AllAg.Mammary_cells [Chip-atlas[Archive

    Full Text Available ALL.Brs.50.AllAg.Mammary_cells mm9 All antigens Breast Mammary cells SRX187508,SRX1...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.50.AllAg.Mammary_cells.bed ...

  2. Bovine mammary stem cells: Transcriptome profiling and the stem cell niche

    Identification and transcriptome analysis of mammary stem cells (MaSC) are important steps toward understanding the molecular basis of mammary epithelial growth, homeostasis and tissue repair. Our objective was to evaluate the molecular profiles of four categories of cells within the bovine mammary ...

  3. LIBO accelerates

    2002-01-01

    The prototype module of LIBO, a linear accelerator project designed for cancer therapy, has passed its first proton-beam acceleration test. In parallel a new version - LIBO-30 - is being developed, which promises to open up even more interesting avenues.

  4. Induction accelerators

    Takayama, Ken

    2011-01-01

    A broad class of accelerators rests on the induction principle whereby the accelerating electrical fields are generated by time-varying magnetic fluxes. Particularly suitable for the transport of bright and high-intensity beams of electrons, protons or heavy ions in any geometry (linear or circular) the research and development of induction accelerators is a thriving subfield of accelerator physics. This text is the first comprehensive account of both the fundamentals and the state of the art about the modern conceptual design and implementation of such devices. Accordingly, the first part of the book is devoted to the essential features of and key technologies used for induction accelerators at a level suitable for postgraduate students and newcomers to the field. Subsequent chapters deal with more specialized and advanced topics.

  5. Mammary blood flow regulation in the nursing rabbit

    Cardiac output and mammary blood flow distribution prior to and after suckling were studied in 10 nursing rabbits by means of radionuclide-labeled microspheres. Suckling was followed by a 5.8% rise in cardiac output and a 20.4% rise in mammary blood flow. Determinations of intraglandular blood flow distribution have shown that there was a 43% increase in blood flow to the glands suckled from as compared to a 22.7% rise to the contralateral untouched glands and a 4.9% rise in the remainder of untouched glands. The conclusion is that a local mechanism may be involved in the regulation of mammary blood flow in the nursing rabbit

  6. Survivin and related proteins in canine mammary tumors: immunohistochemical expression.

    Bongiovanni, L; Romanucci, M; Malatesta, D; D'Andrea, A; Ciccarelli, A; Della Salda, L

    2015-03-01

    Survivin is reexpressed in most human breast cancers, where its expression has been associated with tumor aggressiveness, poor prognosis, and poor response to therapy. Survivin expression was evaluated in 41 malignant canine mammary tumors (CMTs) by immunohistochemistry, in relation to histological grade and stage, and correlated with that of some related molecules (β-catenin, caspase 3, heat shock proteins) to understand their possible role in canine mammary tumorigenesis. An increase in nuclear survivin expression, compared with healthy mammary glands, was observed in CMTs, where nuclear immunolabeling was related to the presence of necrosis. No statistically significant relation was found between the expression of the investigated molecules and the histological grade or stage. The present study may suggest an important involvement of survivin in CMT tumorigenesis. Its overexpression in most of the cases evaluated might suggest that targeting survivin in CMTs may be a valid anticancer therapy. PMID:24686389

  7. Mammary remodeling in primiparous and multiparous dairy goats during lactation

    Safayi, Sina; Theil, Peter Kappel; Elbrønd, Vibeke Sødring;

    2010-01-01

    obtained from both mammary glands of 3 PP and 6 MP (=2 parity) dairy goats at parturition (d 1), d 10, 60, and 180 of lactation. Gene transcription relating to MEC turnover and vascular function was quantified by real-time reverse transcription-PCR, mammary morphology was characterized (quantitative...... histology), and cell turnover was determined (terminal deoxynucleotidyl transferase dUTP nick end labeling assay and Ki-67). Primiparous glands showed higher expression for the genes involved in angiogenesis; namely, vascular endothelial growth factor receptor 2, and angiopoietin 1 and 2 and their receptor......, a few days after parturition (d 10). Primiparous glands also had higher rates of MEC proliferation in early lactation. It therefore appears that initiation of lactation is associated with development and growth of the mammary gland into early lactation, which continues for a longer period in PP...

  8. Xenobiotic-metabolizing enzymes in canine mammary tumours.

    Kumaraguruparan, R; Subapriya, R; Balachandran, C; Manohar, B Murali; Thangadurai, A; Nagini, S

    2006-09-01

    Mammary tumours are the most common neoplasms in female dogs. The present study was designed to evaluate the relationship between different clinical stages with activities of phase I and phase II carcinogen-metabolizing enzymes in canine mammary tumours. The levels of cytochrome P450 and cytochrome b5 and the activities of glutathione S-transferase (GST), gamma-glutamyl transpeptidase (GGT), DT-diaphorase (DTD) and NADPH diaphorase in tumour tissues of 25 bitches was estimated. Enhanced levels of cytochrome P450 and b5 and phase II enzyme activities were observed in tumour tissues compared to the corresponding uninvolved adjacent tissues. The magnitude of the changes in phase I and phase II enzyme status was, however, more pronounced in stages I and II compared to stages III and IV. The results suggest that the balance between phase I carcinogen activation and phase II detoxification systems may play an important role in canine mammary tumour development. PMID:16014333

  9. The effects of spaceflight on mammary metabolism in pregnant rats

    Plaut, K.; Maple, R.; Vyas, C.; Munaim, S.; Darling, A.; Casey, T.; Alberts, J. R.

    1999-01-01

    The effects of spaceflight on mammary metabolism of 10 pregnant rats was measured on Day 20 of pregnancy and after parturition. Rats were flown on the space shuttle from Day 11 through Day 20 of pregnancy. After their return to earth, glucose oxidation to carbon dioxide increased 43% (P Casein mRNA and gross histology were not altered at Day 20 of pregnancy. Six rats gave birth (on Day 22 to 23 of pregnancy) and mammary metabolic activity was measured immediately postpartum. The earlier effects of spaceflight were no longer apparent. There was also no difference in expression of beta-casein mRNA. It is clear from these studies that spaceflight does not impair the normal development of the mammary gland, its ability to use glucose, nor the ability to express mRNA for a major milk protein.

  10. Malignant mammary tumor in female dogs: environmental contaminants

    Bissacot Denise Z

    2010-06-01

    Full Text Available Abstract Mammary tumors of female dogs have greatly increased in recent years, thus demanding rapid diagnosis and effective treatment in order to determine the animal survival. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adjacent adipose tissue of canine mammary tumor. High Precision Liquid Chromatography - HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in nine female dogs, without predilection for breed or age. After surgery, masses were carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor were collected to detect of environmental contaminants. The identified pyrethroids were allethrin, cyhalothrin, cypermethrin, deltamethrin and tetramethrin, with a contamination level of 33.3%. Histopathology demonstrated six female dogs (66.7% as having complex carcinoma and three (33.3% with simple carcinoma. From these tumors, seven (77.8% presented aggressiveness degree III and two (22.2% degree I. Five tumors were positive for estrogen receptors in immunohistochemical analysis. The contamination level was observed in more aggressive tumors. This was the first report in which the level of environmental contaminants could be detected in adipose tissue of female dogs with malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis. Hence, the dog may be used as a sentinel animal for human breast cancer, since human beings share the same environment and basically have the same eating habits.

  11. Immunohistochemical detection of estrogen receptors in canine mammary tumors

    Elena Atanaskova Petrov

    2016-03-01

    Full Text Available Mammary tumors are among the most common neoplasms in intact female dogs.They have a complex morphology, usually affecting middle age and older bitches. Almost 50% of the mammary tumors in dogs are malignant neoplasms. Prognosis is based on several factors: stage, age, tumor size, metastasis, histopathology, ovariectomy status and hormone-receptor activity. Immunohistochemical (IHC measurement has become increasingly an important diagnostic and prognostic parameter, with the development of monoclonal antibodies against nuclear estrogen and progestin receptors. The aim of this study was to detect the presence of ER receptors in malignant canine mammary tumors and to identify their association with the clinical course of the tumor. Mammary tumor samples have been obtained by mastectomy from dogs presented at our clinic. Detailed clinical examination, CBC and basic serum biochemical profile were performed in all patients. Surgery was the only treatment. Histopathological examination and immunohistochemical detection of estrogen α receptors (ERα was performed on 8 formalin-fixed, paraffin-embedded tissue samples, using the PT LINK immunoperoxidase technique. Histopathological examination of the mammary tumor samples (n=11 revealed tubular adenocarcinoma (n=6,54.5% and ductal adenocarcinoma (n=3, 27.3%, one patient with benign adenoma and one with mastitis. Patients with positive ER tumors are alive, without remission, while 3 of the patients that were ER negative died due to lung metastases. According to our results, it can be concluded that the appearance and development of canine mammary tumors is highly connected with ovarian steroid hormones and that immunostaining of the tumors may be used as a good prognostic parameter in these patients.

  12. Functional Interactions between 17β-Estradiol and Progesterone Regulate Autophagy during Acini Formation by Bovine Mammary Epithelial Cells in 3D Cultures

    Katarzyna Zielniok

    2014-01-01

    Full Text Available Mammary gland epithelium forms a network of ducts and alveolar units under control of ovarian hormones: 17-beta-estradiol (E2 and progesterone (P4. Mammary epithelial cells (MECs cultured on reconstituted basement membrane (rBM form three-dimensional (3D acini composed of polarized monolayers surrounding a lumen. Using the 3D culture of BME-UV1 bovine MECs we previously demonstrated that autophagy was induced in the centrally located cells of developing spheroids, and sex steroids increased this process. In the present study we showed that E2 and P4 enhanced the expression of ATG3, ATG5, and BECN1 genes during acini formation, and this effect was accelerated in the presence of both hormones together. The stimulatory action of E2 and P4 was also reflected by increased levels of Atg5, Atg3, and LC3-II proteins. Additionally, the activity of kinases involved in autophagy regulation, Akt, ERK, AMPK, and mTOR, was examined. E2 + P4 slightly increased the level of phosphorylated AMPK but diminished phosphorylated Akt and mTOR on day 9 of 3D culture. Thus, the synergistic actions of E2 and P4 accelerate the development of bovine mammary acini, which may be connected with stimulation of ATGs expression, as well as regulation of signaling pathways (PI3K/Akt/mTOR; AMPK/mTOR involved in autophagy induction.

  13. Lymph Drainage of the Mammary Glands in Female Cats

    Raharison, Fidiniaina; Sautet, Jean

    2006-01-01

    The mammary gland is a common site of neoplasms in the female cat. All the malignant tumors metastasize to a lesser or a greater extent through the lymphatic system. However, the anatomical knowledge of this system is not sufficiently well known in cats to develop a reasoned model for the extirpation of these glands in case of malignant tumors. A study of the lymph drainage in 50 female cats was done by indirect injection in vivo of India ink inside the mammary parenchyma. After a waiting inte...

  14. Evaluation of Mammary Gland Development and Function in Mouse Models

    Plante, Isabelle; Stewart, Michael K.G.; Laird, Dale W.

    2011-01-01

    The human mammary gland is composed of 15-20 lobes that secrete milk into a branching duct system opening at the nipple. Those lobes are themselves composed of a number of terminal duct lobular units made of secretory alveoli and converging ducts1. In mice, a similar architecture is observed at pregnancy in which ducts and alveoli are interspersed within the connective tissue stroma. The mouse mammary gland epithelium is a tree like system of ducts composed of two layers of cells, an inner la...

  15. Coronary bypass using bilateral internal mammary arteries in an achondroplast.

    Alassal, Mohamed Abdulwahab; Youssef, Mostafa; Koudieh, Mohammed

    2015-01-01

    Coronary bypass grafting for ischemic heart disease in achondroplastic dwarfs is very rare. Shortage of veins and inadequate vein quality may cause difficulties during surgery. Only 2 cases of coronary bypass surgery in an achondroplastic dwarf, in which the left internal mammary artery and vein grafts were used, have been reported. We describe the case of a 55-year-old male achondroplastic dwarf who had triple-vessel coronary disease and underwent successful coronary bypass surgery using one saphenous vein graft and bilateral internal mammary artery grafts. The anatomic and surgical challenges in achondroplasia are highlighted. PMID:24887865

  16. Radiogenic neoplasia in thyroid and mammary clonogens

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. Previous results indicated that these clonogens are the precursor cells of radiogenic cancer, and that initiation, is common event at the clonegenic cell level. Detailed information on the physiologic control of clonogen proliferation, differentiation, and total numbers is thus essential to an understanding of the carcinogenic process. We report here studies on investigations on the relationships between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamus-pituitary feedback axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH-(thyrotropin-) responsive sub- population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and a large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cell interactions during the neoplastic process

  17. The mammary glands of the Amazonian manatee, Trichechus inunguis (Mammalia: Sirenia): morphological characteristics and microscopic anatomy.

    Rodrigues, Fernanda Rosa; da Silva, Vera Maria Ferreira; Barcellos, José Fernando Marques

    2014-08-01

    The mammaries from carcasses of two female Amazonian manatees were examined. Trichechus inunguis possesses two axillary mammaries beneath the pectoral fins, one on each side of the body. Each papilla mammae has a small hole on its apex--the ostium papillare. The mammaries are covered by a stratified squamous keratinized epithelium. The epithelium of the mammary ducts became thinner more deeply in the tissue and varied from stratified to simple cuboidal. There was no evidence of glandular activity or secretion into the ducts of the mammary glands. PMID:24920139

  18. The t10,c12 isomer of conjugated linoleic acid stimulates mammary tumorigenesis in transgenic mice overexpressing erbB2 in the mammary epithelium

    Ip, Margot M.; McGee, Sibel O.; Masso-Welch, Patricia A.; IP, CLEMENT; Meng, Xiaojing; Ou, Lihui; Shoemaker, Suzanne

    2007-01-01

    Conjugated linoleic acid (CLA), a family of isomers of octadecadienoic acid, inhibits rat mammary carcinogenesis, angiogenesis, and lung metastasis from a transplantable mammary tumor. c9,t11-CLA, the predominant isomer in dairy products, and t10,c12-CLA, a component of CLA supplements, are equally effective. The objective of the current studies was to test the efficacy of these two CLA isomers in a clinically relevant breast cancer model. Transgenic mice overexpressing erbB2 in the mammary e...

  19. A mouse mammary tumor virus mammary gland enhancer confers tissue-specific but not lactation-dependent expression in transgenic mice.

    Mok, E; Golovkina, T V; Ross, S R

    1992-01-01

    The long terminal repeat (LTR) of mouse mammary tumor virus (MMTV) is known to contain a number of transcriptional regulatory elements, including glucocorticoid response elements. In this study, we showed that a mammary gland/salivary gland enhancer found in the LTR of this virus directs expression of a heterologous promoter to both virgin and lactating mammary glands in transgenic mice. Using transgenic mice containing hybrid gene constructs with various deletions of the LTR sequences linked...

  20. Identification and characterization of cancer initiating cells from BRCA1 related mammary tumors using markers for normal mammary stem cells

    Vassilopoulos, Athanassios; Wang, Rui-Hong; Petrovas, Constantinos; Ambrozak, David; Koup, Richard; Deng, Chu-Xia

    2008-01-01

    It is hypothesized that cancer stem cells arise either from normal stem cells or from progenitor cells that have gained the ability to self-renew. Here we determine whether mammary cancer stem cells can be isolated by using antibodies that have been used for the isolation of normal mammary stem cells. We show that BRCA1 mutant cancer cell lines contained a subpopulation of CD24+CD29+ or CD24+CD49f+ cells that exhibited increased proliferation and colony forming ability in vitro, and enhanced ...

  1. Overexpression of Human Cripto-1 in Transgenic Mice Delays Mammary Gland Development and Differentiation and Induces Mammary Tumorigenesis

    Sun, Youping; Strizzi, Luigi; Raafat, Ahmed; Hirota, Morihisa; Bianco, Caterina; Feigenbaum, Lionel; Kenney, Nicholas; Wechselberger, Christian; Callahan, Robert; Salomon, David S.

    2005-01-01

    Overexpression of Cripto-1 has been reported in several types of human cancers including breast cancer. To investigate the role of human Cripto-1 (CR-1) in mammary gland development and tumorigenesis, we developed transgenic mice that express the human CR-1 transgene under the regulation of the whey acidic protein (WAP) promoter in the FVB/N mouse background. The CR-1 transgene was detected in the mammary gland of 15-week-old virgin WAP-CR-1 female mice that eventually developed hyperplastic ...

  2. Quantification of mammary organoid toxicant response and mammary tissue motility using OCT fluctuation spectroscopy (Conference Presentation)

    Yu, Xiao; Blackmon, Richard L.; Carabas-Hernendez, Patricia; Fuller, Ashley; Troester, Melissa A.; Oldenburg, Amy L.

    2016-03-01

    Mammary epithelial cell (MEC) organoids in 3D culture recapitulate features of breast ducts in vivo. OCT has the ability to monitor the evolution of MEC organoids non-invasively and longitudinally. The anti-cancer drug Doxorubicin (Dox) is able to inhibit proliferation of cancer cells and has been widely used for chemotherapy of breast cancers; while environmental toxins implicated in breast cancer such as estrogen regulates mammary tumor growth and stimulates the proliferation and metastatic potential of breast cancers. Here we propose a quantitative method for measuring motility of breast cells in 3D cultures based upon OCT speckle fluctuation spectroscopy. The metrics of the inverse power-law exponent (α) and fractional modulation amplitude (M) were extracted from speckle fluctuation spectra. These were used to quantify the responses of MEC organoids to Dox, and estrogen. We investigated MEC organoids comprised of two different MEC lines: MCF10DCIS.com exposed to Dox, and MCF7 exposed to estrogen. We found an increase (p<0.001) in α of MEC along time (t=0, 1 hour, 24 hours, 48 hours and 6 days) at each dose of Dox (0, 1 μM and 10 μM), indicating lower fluctuation intensity at higher frequencies. We also observed a decrease (p<0.001) in M for increasing time. However, both α and M of MCF7 treated with estrogen (0, 1 nM and 10 nM) exhibited the opposite trend along time. This novel technology provides rapid and non-invasive measurements of the effects of toxicants on MEC motility for understanding breast cancer development and assessing anti-cancer drugs.

  3. ApcMin, a mutation in the murine Apc gene, predisposes to mammary carcinomas and focal alveolar hyperplasias.

    Moser, A R; Mattes, E M; Dove, W. F.; Lindstrom, M.J.; Haag, J D; Gould, M N

    1993-01-01

    ApcMin (Min, multiple intestinal neoplasia) is a point mutation in the murine homolog of the APC gene. Min/+ mice develop multiple intestinal adenomas, as do humans carrying germ-line mutations in APC. Female mice carrying Min are also prone to develop mammary tumors. Min/+ mammary glands are more sensitive to chemical carcinogenesis than are +/+ mammary glands. Transplantation of mammary cells from Min/+ or +/+ donors into +/+ hosts demonstrates that the propensity to develop mammary tumors ...

  4. Can widely used cell type markers predict the suitability of immortalized or primary mammary epithelial cell models?

    Ontsouka, Edgar; Bertschi, Janique Sabina; Huang, Xiao; Lüthi, Michael; Müller, Stefan Jürg; Albrecht, Christiane

    2016-01-01

    BACKGROUND Mammary cell cultures are convenient tools for in vitro studies of mammary gland biology. However, the heterogeneity of mammary cell types, e.g., glandular milk secretory epithelial or myoepithelial cells, often complicates the interpretation of cell-based data. The present study was undertaken to determine the relevance of bovine primary mammary epithelial cells isolated from American Holstein (bMECUS) or Swiss Holstein-Friesian (bMECCH) cows, and of primary bovine mammary alv...

  5. Can widely used cell type markers predict the suitability of immortalized or primary mammary epithelial cell models?

    Ontsouka, Edgar Corneille; Bertschi, Janique Sabina; Huang, Xiao; Lüthi, Michael; Müller, Stefan; Albrecht, Christiane

    2016-01-01

    Background Mammary cell cultures are convenient tools for in vitro studies of mammary gland biology. However, the heterogeneity of mammary cell types, e.g., glandular milk secretory epithelial or myoepithelial cells, often complicates the interpretation of cell-based data. The present study was undertaken to determine the relevance of bovine primary mammary epithelial cells isolated from American Holstein (bMECUS) or Swiss Holstein–Friesian (bMECCH) cows, and of primary bovine mammary alveola...

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

    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

  7. Interrogation of the rat mammary gland using intraductal impedance spectroscopy

    Extant technologies for the detection of breast cancer exploit changes in the morphology of the mammary ductal epithelial network and can involve ionizing radiation. Intraductal surveillance of mammary epithelium has the potential to allow for earlier detection based on changes in function of the epithelium. This study investigated the feasibility of using intraductal impedance spectroscopy (IIS) to assess changes in resistance in the mammary epithelium in a small group of female rats in resting, pregnant and ultimately lactating states. In resting rats, intraductal surveillance was able to detect only a single resistive capacitance (RC). In pregnant animals, a second RC became evident in the frequency range between 1 and 190 Hz. The real resistance of this low frequency RC increased when measurements were made after the animals had begun lactating. Equivalent circuit modeling revealed this increase to be a 1.7-fold change from pregnancy to lactation. A model of tight junction closure in the context of ductal expansion is proposed. These results suggest that physiologic measurements can be made in rodent mammary epithelium using this technique allowing for assessment of function in normal and disease states

  8. Detection of Mouse Mammary Tumour Virus in house mice

    Steffensen, Lise K; Leirs, Herwig; Heiberg, Ann-Charlotte

    The prevalence of human breast cancer (HBC) is affected by several parameters. For the past decades MMTV, Mouse Mammary Tumor Virus, known to cause breast cancer in mice, has been hypothesized to affect the frequency of hormone dependent HBC. Though conclusive evidence has not been produced, still...

  9. Aflatoxins ingestion and canine mammary tumors: There is an association?

    Frehse, M S; Martins, M I M; Ono, E Y S; Bracarense, A P F R L; Bissoqui, L Y; Teixeira, E M K; Santos, N J R; Freire, R L

    2015-10-01

    The aim of this study was to determine the presence of mycotoxins on dogs feed and to explore the potential association between mycotoxins exposure and the chance of mamary tumors in a case-control study. The study included 256 female dogs from a hospital population, 85 with mammary tumors (case group) and 171 without mammary tumors (control group). An epidemiological questionnaire was applied to both groups, and the data were analyzed by the EpiInfo statistical package. For the study, 168 samples of the feed offered to dogs were analyzed for the presence of aflatoxins, fumonisins and zearalenone by high-performance liquid chromatography. Mycotoxins were found in 79 samples (100%) in the case group and 87/89 (97.8%) in the control group. Mycotoxins were detected in all types of feed, regardless feed quality. Level of aflatoxin B1 (p = 0.0356, OR = 2.74, 95%, CI 1.13 to 6.60), aflatoxin G1 (AFG1) (p = 0.00007, OR = 4.60, 95%, CI = 2.16 to 9.79), and aflatoxin G2 (AFG2) (p = 0.0133, OR = 9.91, 95%, CI 1.21 to 81.15) were statistically higher in case of mammary cancer. In contrast, neutering was a protective factor for mammary cancer (p = 0.0004, OR = 0.32, 95%, CI = 0.17 to 0.60). PMID:26271706

  10. Collagen density promotes mammary tumor initiation and progression

    Knittel Justin G

    2008-04-01

    Full Text Available Abstract Background Mammographically dense breast tissue is one of the greatest risk factors for developing breast carcinoma. Despite the strong clinical correlation, breast density has not been causally linked to tumorigenesis, largely because no animal model has existed for studying breast tissue density. Importantly, regions of high breast density are associated with increased stromal collagen. Thus, the influence of the extracellular matrix on breast carcinoma development and the underlying molecular mechanisms are not understood. Methods To study the effects of collagen density on mammary tumor formation and progression, we utilized a bi-transgenic tumor model with increased stromal collagen in mouse mammary tissue. Imaging of the tumors and tumor-stromal interface in live tumor tissue was performed with multiphoton laser-scanning microscopy to generate multiphoton excitation and spectrally resolved fluorescent lifetimes of endogenous fluorophores. Second harmonic generation was utilized to image stromal collagen. Results Herein we demonstrate that increased stromal collagen in mouse mammary tissue significantly increases tumor formation approximately three-fold (p p Conclusion This study provides the first data causally linking increased stromal collagen to mammary tumor formation and metastasis, and demonstrates that fundamental differences arise and persist in epithelial tumor cells that progressed within collagen-dense microenvironments. Furthermore, the imaging techniques and signature identified in this work may provide useful diagnostic tools to rapidly assess fresh tissue biopsies.

  11. The epigenetic landscape of mammary gland development and functional differentiation

    Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conf...

  12. Heterogeneity of mammary lesions represent molecular differences

    Human breast cancer is a heterogeneous disease, histopathologically, molecularly and phenotypically. The molecular basis of this heterogeneity is not well understood. We have used a mouse model of DCIS that consists of unique lines of mammary intraepithelial neoplasia (MIN) outgrowths, the premalignant lesion in the mouse that progress to invasive carcinoma, to understand the molecular changes that are characteristic to certain phenotypes. Each MIN-O line has distinguishable morphologies, metastatic potentials and estrogen dependencies. We utilized oligonucleotide expression arrays and high resolution array comparative genomic hybridization (aCGH) to investigate whole genome expression patterns and whole genome aberrations in both the MIN-O and tumor from four different MIN-O lines that each have different phenotypes. From the whole genome analysis at 35 kb resolution, we found that chromosome 1, 2, 10, and 11 were frequently associated with whole chromosome gains in the MIN-Os. In particular, two MIN-O lines had the majority of the chromosome gains. Although we did not find any whole chromosome loss, we identified 3 recurring chromosome losses (2F1-2, 3E4, 17E2) and two chromosome copy number gains on chromosome 11. These interstitial deletions and duplications were verified with a custom made array designed to interrogate the specific regions at approximately 550 bp resolution. We demonstrated that expression and genomic changes are present in the early premalignant lesions and that these molecular profiles can be correlated to phenotype (metastasis and estrogen responsiveness). We also identified expression changes associated with genomic instability. Progression to invasive carcinoma was associated with few additional changes in gene expression and genomic organization. Therefore, in the MIN-O mice, early premalignant lesions have the major molecular and genetic changes required and these changes have important phenotypic significance. In contrast, the changes

  13. Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells

    Hirai, H.; Lochter, A.; Galosy, S.; Koshida, S.; Niwa, S.; Bissell, M.J.

    1997-10-13

    Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized.

  14. Comparative expression pathway analysis of human and canine mammary tumors

    Marconato Laura

    2009-03-01

    Full Text Available Abstract Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.

  15. Tandem accelerators

    After the installation of Ti-acceleration tubes and substantial modifications and additions to the EN tandem accelerator the performance of the machine has stabilized. The voltage behaviour of the tubes obviously improves as conditioning times necessary to run up to 6 MV decrease. A gridded lens has been added at the entrance of the first acceleration tube, and a second foil stripper is now installed in the short dead section between the high-energy tubes. The MP tandem also has been running stably during most of the year. However, beam instabilities originating from the last tube section and wear problems at the low-energy set of pelletron-chains caused some loss of beam time. During the fall, one set of pelletron charging chains has to be replaced after 49,000 hours of operation. In the course of the year, the MP and the EN tandem accelerators finished their 100,000th and 150,000th hours of operations, respectively. Preparations for the installation of the 3 MV negative heavy ion injector for the MP are progressing steadily. External beam transport, terminal ion optics, and data acquisition and control systems are to a major extent completed; the integration of the terminal power supplies has started. After the final assembly of the accelerator column structure, first voltage runs can be performed. (orig.)

  16. Functional characterization of Mammary Gland Protein-40, a chitinase-like glycoprotein expressed during mammary gland apoptosis.

    Anand, Vijay; Jaswal, Shalini; Singh, Surender; Kumar, Sudarshan; Jena, Manoj Kumar; Verma, Arvind Kumar; Yadav, Munna Lal; Janjanam, Jagadeesh; Lotfan, Masoud; Malakar, Dhruba; Dang, Ajay Kumar; Mohanty, Tushar Kumar; Kaushik, Jai Kumar; Mohanty, Ashok Kumar

    2016-02-01

    MGP-40 is a chitinase-like protein which is over expressed during mammary gland involution. However, its physiological function in the mammary gland is poorly understood. In the present investigation, we have reported the functional significance of buffalo specific MGP-40 in the mammary gland by using an in vitro model of the buffalo mammary epithelial cell (BuMEC) line. MGP-40 was highly up regulated in BuMECs in serum starved condition as well as after treatment with prolactin suggesting its role in the stress response. Subsequently, to study the effect of MGP-40 on BuMECs, the cells were transfected with a mammalian expression construct of pCI neo harboring MGP-40 gene. It was observed that over expression of MGP-40 enhanced proliferation of BuMECs and protected the cells from apoptosis under serum free condition. In contrast, MGP-40 attenuated the mitogenic effect of insulin in BuMECs. Besides, over expression of the MGP-40 reduced dome formation, acinar polarization and casein synthesis in BuMECs in the presence of lactogenic hormones, it also induced Stat3 phosphorylation and epithelial to mesenchymal transition (EMT) -like features. Together, our data suggest that MGP-40 is involved in protection of BuMECs under stress conditions, inhibits cellular differentiation and induces EMT-like features. A schematic diagram depicting possible association of MGP-40 in various molecular pathways has been presented. PMID:26659075

  17. Transcriptomic signature of Bexarotene (Rexinoid LGD1069 on mammary gland from three transgenic mouse mammary cancer models

    Bissonnette Reid P

    2008-09-01

    Full Text Available Abstract Background The rexinoid bexarotene (LGD1069, Targretin is a highly selective retinoid × receptor (RXR agonist that inhibits the growth of pre-malignant and malignant breast cells. Bexarotene was shown to suppress the development of breast cancer in transgenic mice models without side effects. The chemopreventive effects of bexarotene are due to transcriptional modulation of cell proliferation, differentiation and apoptosis. Our goal in the present study was to obtain a profile of the genes modulated by bexarotene on mammary gland from three transgenic mouse mammary cancer models in an effort to elucidate its molecular mechanism of action and for the identification of biomarkers of effectiveness. Methods Serial analysis of gene expression (SAGE was employed to profile the transcriptome of p53-null, MMTV-ErbB2, and C3(1-SV40 mammary cells obtained from mice treated with bexarotene and their corresponding controls. Results This resulted in a dataset of approximately 360,000 transcript tags representing over 20,000 mRNAs from a total of 6 different SAGE libraries. Analysis of gene expression changes induced by bexarotene in mammary gland revealed that 89 genes were dysregulated among the three transgenic mouse mammary models. From these, 9 genes were common to the three models studied. Conclusion Analysis of the indicated core of transcripts and protein-protein interactions of this commonly modulated genes indicate two functional modules significantly affected by rexinoid bexarotene related to protein biosynthesis and bioenergetics signatures, in addition to the targeting of cancer-causing genes related with cell proliferation, differentiation and apoptosis.

  18. Regulation of mammary stem cell population with dietary intake of soy protein isolate reveals novel mechanisms for diet-mediated control of mammary tumorigenesis

    Breast cancer risk is highly modified by environmental factors including diet. Previously, we showed that dietary intake of soy protein isolate (SPI) decreased mammary tumor incidence and increased mammary tumor latency in rats relative to those fed a control casein (CAS) diet, when exposed to the c...

  19. Particle acceleration

    Vlahos, L.; Machado, M. E.; Ramaty, R.; Murphy, R. J.; Alissandrakis, C.; Bai, T.; Batchelor, D.; Benz, A. O.; Chupp, E.; Ellison, D.

    1986-01-01

    Data is compiled from Solar Maximum Mission and Hinothori satellites, particle detectors in several satellites, ground based instruments, and balloon flights in order to answer fundamental questions relating to: (1) the requirements for the coronal magnetic field structure in the vicinity of the energization source; (2) the height (above the photosphere) of the energization source; (3) the time of energization; (4) transistion between coronal heating and flares; (5) evidence for purely thermal, purely nonthermal and hybrid type flares; (6) the time characteristics of the energization source; (7) whether every flare accelerates protons; (8) the location of the interaction site of the ions and relativistic electrons; (9) the energy spectra for ions and relativistic electrons; (10) the relationship between particles at the Sun and interplanetary space; (11) evidence for more than one acceleration mechanism; (12) whether there is single mechanism that will accelerate particles to all energies and also heat the plasma; and (13) how fast the existing mechanisms accelerate electrons up to several MeV and ions to 1 GeV.

  20. Accelerator design

    The feasibility of constructing a TeV region electron-positron linear collider in Japan is discussed. The design target of the collider is given as follows: Energy, 1 TeV + 1 TeV; luminosity, 1032-1033/cm2/s; total length, 25km; electric power, 250MW; energy dispersion, 1%-10%; the start of the first experiment, early 1990s. For realizing the above target, the following research and developmental works are necessary. (a) Development of an acceleration tube with short filling time and high shunt resistance. (b) Short pulse microwave source with high peak power. (c) High current, single bunch linac. (d) Beam dynamics. As for the acceleration tube, some possibility is considered: For example, the use of DAW (Disk and Washer) which is being developed for TRISTAN as a traveling-wave tube; and the Jungle Gym-type acceleration tube. As a promising candidate for the microwave source, the Lasertron has been studied. The total cost of the collider construction is estimated to be about 310 billion yen, of which 120 billion yen is for the tunnel and buildings, and 190 billion yen for the accelerator facilities. The operation cost is estimated to be about 3 billion yen per month. (Aoki, K.)

  1. Accelerator operations

    This section is concerned with the operation of both the tandem-linac system and the Dynamitron, two accelerators that are used for entirely different research. Developmental activities associated with the tandem and the Dynamitron are also treated here, but developmental activities associated with the superconducting linac are covered separately because this work is a program of technology development in its own right

  2. Optimization and characterization of an in vitro bovine mammary cell culture system to study regulation of milk protein synthesis and mammary differentiation

    A long term bovine mammary cell culture system that maintains normal mammary cell function was established and optimized to study milk protein synthesis and secretion and mammary differentiation. This culture system used bovine mammary acini isolated from developing or lactating mammary gland by enzymatic dissociation, and cryopreserved until thawed and plated for growth in vitro for these studies. Cells in M199 with lactogenic hormones ± fetal calf serum (FCS) were cultured on plastic, 100ul and 500ul type I collagen, and Matrigel, or embedded within type I collagen. Cell morphology, cell number, and total TCA-precipitable 35S-labelled proteins were monitored. Milk protein (αs,1-casein, lactoferrin (LF), α-lactalbumin, and β-lactoglobulin) secretion and intracellular levels were determined by an ELISA assay

  3. Advanced accelerators

    This report discusses the suitability of four novel particle acceleration technologies for multi-TeV particle physics machines: laser driven linear accelerators (linac), plasma beat-wave devices, plasma wakefield devices, and switched power and cavity wakefield linacs. The report begins with the derivation of beam parameters practical for multi-TeV devices. Electromagnetic field breakdown of materials is reviewed. The two-beam accelerator scheme for using a free electron laser as the driver is discussed. The options recommended and the conclusions reached reflect the importance of cost. We recommend that more effort be invested in achieving a self-consistent range of TeV accelerator design parameters. Beat-wave devices have promise for 1-100 GeV applications and, while not directly scalable to TeV designs, the current generation of ideas are encouraging for the TeV regime. In particular, surfatrons, finite-angle optical mixing devices, plasma grating accelerator, and the Raman forward cascade schemes all deserve more complete analysis. The exploitation of standard linac geometry operated in an unconventional mode is in a phase of rapid evolution. While conceptual projects abound, there are no complete designs. We recommend that a fraction of sponsored research be devoted to this approach. Wakefield devices offer a great deal of potential; trades among their benefits and constraints are derived and discussed herein. The study of field limitation processes has received inadequate attention; this limits experiment designers. The costs of future experiments are such that investment in understanding these processes is prudent. 34 refs., 12 figs., 3 tabs

  4. Autocrine-paracrine regulation of the mammary gland.

    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

  5. Heat shock protein expression in canine malignant mammary tumours

    Abnormal levels of Heat Shock Proteins (HSPs) have been observed in many human neoplasms including breast cancer and it has been demonstrated that they have both prognostic and therapeutic implications. In this study, we evaluated immunohistochemical expression of HSPs in normal and neoplastic canine mammary glands and confronted these results with overall survival (OS), in order to understand the role of HSPs in carcinogenesis and to establish their potential prognostic and/or therapeutic value. Immunohistochemical expression of Hsp27, Hsp72, Hsp73 and Hsp90 was evaluated in 3 normal canine mammary glands and 30 malignant mammary tumours (10 in situ carcinomas, 10 invasive carcinomas limited to local structures without identifiable invasion of blood or lymphatic vessels, 10 carcinomas with invasion of blood or lymphatic vessels and/or metastases to regional lymph nodes). A semi-quantitative method was used for the analysis of the results. Widespread constitutive expression of Hsp73 and Hsp90 was detected in normal tissue, Hsp72 appeared to be focally distributed and Hsp27 showed a negative to rare weak immunostaining. In mammary tumours, a significant increase in Hsp27 (P < 0.01), Hsp72 (P < 0.05) and Hsp90 (P < 0.01) expression was observed as well as a significant reduction in Hsp73 (P < 0.01) immunoreactivity compared to normal mammary gland tissue. Hsp27 demonstrated a strong positivity in infiltrating tumour cells and metaplastic squamous elements of invasive groups. High Hsp27 expression also appeared to be significantly correlated to a shorter OS (P = 0.00087). Intense immunolabelling of Hsp72 and Hsp73 was frequently detected in infiltrative or inflammatory tumour areas. Hsp90 expression was high in all tumours and, like Hsp73, it also showed an intense positivity in lymphatic emboli. These results suggest that Hsp27, Hsp72 and Hsp90 are involved in canine mammary gland carcinogenesis. In addition, Hsp27 appears to be implicated in tumour invasiveness and

  6. Cadmium in milk and mammary gland in rats and mice

    The purpose of the present investigation was to study the uptake of cadmium in mammary tissue, effects on milk secretion and composition, and lactational transport of cadmium to the sucklings. Cadmium exposure during lactation resulted in retention of cadmium in the mammary tissue in mice and rats. The uptake of cadmium in the mammary tissue was rapid, as shown in lactating mice by whole-body autoradiography 4 h after an intravenous injection of a tracer dose of 109CdCl2. Retention of cadmium in kidneys of suckling pups was observed in the autoradiograms at 7 days after exposure of the dams. Lactating rats were intravenously infused with 109CdCl2 in 0.9% saline via osmotic minipumps from day 3 to day 16 after parturition. The cadmium dose given was 0, 8.8, 62 and 300 μg Cd/kg body wt. per day. Plasma and milk were collected at day 10 and 16 after parturition. Plasma cadmium levels in dams increased from day 10 to day 16. Cadmium levels were higher in milk than in plasma, with milk/plasma ratios varying from 2 to 6. Zinc levels in milk were positively correlated to cadmium levels in milk (r2=0.26; P=0.03). In milk, 109Cd was distributed in fat (46-52%), casein fraction (40-46%), and whey fraction (6-8%). There was a high correlation between cadmium concentrations in pups' kidney and cadmium concentrations in dam's milk (r2=0.98; P 109Cd was bound to metallothionein in mammary tissue. The fraction of radiolabelled cadmium bound to metallothionein increased in a dose-dependent manner in both the liver (88-98%) and mammary tissue (57-80%). The present results indicate a low transfer of cadmium to the suckling pup, which might be due to binding of cadmium to metallothionein in the mammary tissue. However, during the susceptible developmental period even a low cadmium exposure may be of concern. (orig.)

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

    Hvid, Henning; Klopfleisch, Robert; Vienberg, Sara Gry; Hansen, Bo F.; Thorup, Inger; Jensen, Henrik Elvang; Oleksiewicz, Martin B.

    2011-01-01

    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...... than the expression of the IR-B. By immunohistochemistry, expression of IR and IGF-1R was detected in all mammary gland epithelial cells. Expression of ERα and PR was comparable between mammary gland and ovary, whereas expression of ERβ was lower in mammary gland than in the ovary. Finally, expression...

  8. PUMA Cooperates with p21 to Regulate Mammary Epithelial Morphogenesis and Epithelial-To-Mesenchymal Transition

    Zhang, Yanhong; Yan, Wensheng; Jung, Yong Sam; Chen, Xinbin

    2013-01-01

    Lumen formation is essential for mammary morphogenesis and requires proliferative suppression and apoptotic clearance of the inner cells within developing acini. Previously, we showed that knockdown of p53 or p73 leads to aberrant mammary acinus formation accompanied with decreased expression of p53 family targets PUMA and p21, suggesting that PUMA, an inducer of apoptosis, and p21, an inducer of cell cycle arrest, directly regulate mammary morphogenesis. To address this, we generated multipl...

  9. Proteinases of the mammary gland: developmental regulation in vivo and vectorial secretion in culture

    Talhouk, Rabih S.; CHIN, JENNIE R.; UNEMORI, ELAINE N.; Werb, Zena; Bissell, Mina J.

    1991-01-01

    The extracellular matrix (ECM) is an important regulator of mammary epithelial cell function both in vivo and in culture. Substantial remodeling of ECM accompanies the structural changes in the mammary gland during gestation, lactation and involution. However, little is known about the nature of the enzymes and the processes involved. We have characterized and studied the regulation of cell-associated and secreted mammary gland proteinases active at neutral pH that may be involved in degradat...

  10. Id-1 is not expressed in the luminal epithelial cells of mammary glands

    Uehara, Norihisa; Chou, Yu-Chien; Galvez, Jose J; de-Candia, Paola; Cardiff, Robert D; Benezra, Robert; Shyamala, Gopalan

    2003-01-01

    Background The family of inhibitor of differentiation/DNA binding (Id) proteins is known to regulate development in several tissues. One member of this gene family, Id-1, has been implicated in mammary development and carcinogenesis. Mammary glands contain various cell types, among which the luminal epithelial cells are primarily targeted for proliferation, differentiation and carcinogenesis. Therefore, to assess the precise significance of Id-1 in mammary biology and carcinogenesis, we exami...

  11. Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8

    Hanayama, Rikinari; Nagata, Shigekazu

    2005-01-01

    During the involution of mammary glands, epithelial cells undergo apoptosis and are cleared for the next cycle of lactation. The clearance of apoptotic epithelial cells is mediated by neighboring epithelial cells and by macrophages that migrate into the mammary glands. Here, we report that milk fat globule EGF factor 8 (MFG-E8), a secreted glycoprotein that binds to apoptotic cells by recognizing phosphatidylserine, was expressed by epithelial cells and macrophages in mammary glands and was i...

  12. Adipophilin regulates maturation of cytoplasmic lipid droplets and alveolae in differentiating mammary glands

    Russell, Tanya D.; Schaack, Jerome; Orlicky, David J.; Palmer, Carol; Chang, Benny Hung-Junn; Chan, Lawrence; McManaman, James L.

    2011-01-01

    Milk lipids originate by secretion of triglyceride-rich cytoplasmic lipid droplets (CLDs) from mammary epithelial cells. Adipophilin (ADPH)/Plin2, a member of the perilipin family of CLD binding proteins, is hypothesized to regulate CLD production in these cells during differentiation of the mammary gland into a secretory organ. We tested this hypothesis by comparing CLD accumulation in differentiating mammary glands of wild-type and ADPH-deficient mice. ADPH deficiency did not prevent CLD fo...

  13. Could protein tertiary structure influence mammary transgene expression more than tissue specific codon usage?

    He, Zuyong; Zhao, Yiqiang; Mei, Gui; Li, Ning; Chen, Yaosheng

    2010-01-01

    Animal mammary glands have been successfully employed to produce therapeutic recombinant human proteins. However, considerable variation in animal mammary transgene expression efficiency has been reported. We now consider whether aspects of codon usage and/or protein tertiary structure underlie this variation in mammary transgene expression. Electronic supplementary material The online version of this article (doi:10.1007/s11248-010-9411-8) contains supplementary material, which is available ...

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

    Chatterjee, Sumanta; Bacopulos, Stephanie; Yang, Wenyi; Amemiya, Yutaka; Spyropoulos, Demetri; Raouf, Afshin; Seth, Arun

    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. Result...

  15. Loss of sfrp1 promotes ductal branching in the murine mammary gland

    Gauger Kelly J; Shimono Akihiko; Crisi Giovanna M; Schneider Sallie

    2012-01-01

    Abstract Background Secreted frizzled-related proteins (SFRPs) are a family of proteins that block the Wnt signaling pathway and loss of SFRP1 expression is found in breast cancer along with a multitude of other human cancers. Activated Wnt signaling leads to inappropriate mammary gland development and mammary tumorigenesis in mice. When SFRP1 is knocked down in immortalized non-malignant mammary epithelial cells, the cells exhibit a malignant phenotype which resembles the characteristics obs...

  16. Transgenic Insulin-like Growth Factor-1 stimulates activation of COX-2 signaling in mammary glands

    Tian, Jie; Lambertz, Isabel; Berton, Thomas R.; Rundhaug, Joyce E.; Kiguchi, Kaoru; Shirley, Stephanie H.; DiGiovanni, John; Conti, Claudio J.; Fischer, Susan M.; Fuchs-Young, Robin

    2011-01-01

    Studies show that elevated IGF-1 levels are associated with an increased risk of breast cancer; however, mechanisms through which IGF-1 promotes mammary tumorigenesis in vivo have not been fully elucidated. To assess the possible involvement of COX-2 signaling in the protumorigenic effects of IGF-1 in mammary glands, we used the unique BK5.IGF-1 mouse model in which transgenic (Tg) mice have significantly increased incidence of spontaneous and DMBA–induced mammary cancer compared to wild type...

  17. Bisected, complex N-glycans and galectins in mouse mammary tumor progression and human breast cancer

    Miwa, Hazuki E.; Koba, Wade R; Fine, Eugene J; Giricz, Orsi; Kenny, Paraic A; Stanley, Pamela

    2013-01-01

    Bisected, complex N-glycans on glycoproteins are generated by the glycosyltransferase MGAT3 and cause reduced cell surface binding of galectins. Previously, we showed that MGAT3 reduces growth factor signaling and retards mammary tumor progression driven by the Polyoma middle T antigen (PyMT) expressed in mammary epithelium under the mouse mammary tumor virus (MMTV) promoter. However, the penetrance of the tumor phenotype became variable in mixed FVB/N and C57BL/6 female mice and we therefore...

  18. Effect of glycogen synthase kinase-3 inactivation on mouse mammary gland development and oncogenesis

    Dembowy, J; Adissu, H A; Liu, J. C.; Zacksenhaus, E; Woodgett, J R

    2014-01-01

    Many components of the Wnt/β-catenin signaling pathway have critical functions in mammary gland development and tumor formation, yet the contribution of glycogen synthase kinase-3 (GSK-3α and GSK-3β) to mammopoiesis and oncogenesis is unclear. Here, we report that WAP-Cre-mediated deletion of GSK-3 in the mammary epithelium results in activation of Wnt/β-catenin signaling and induces mammary intraepithelial neoplasia that progresses to squamous transdifferentiation and development of adenosqu...

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

    Lund, Leif R.; Rømer, John; Thomasset, Nicole; Solberg, Helene; Pyke, Charles; Bissell, Mina J.; Danø, 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 ...

  20. Development of Foreign Mammary Epithelial Morphology in the Stroma of Immunodeficient Mice

    Gat Rauner; Amos Leviav; Eliezer Mavor; Itamar Barash

    2013-01-01

    Systemic growth and branching stimuli, and appropriate interactions with the host stroma are essential for the development of foreign epithelia in the mammary gland of immunodeficient mice. These factors were manipulated to promote and investigate the generation of representative bovine epithelial morphology in the transplanted mouse mammary stroma. The bovine mammary epithelium is unique in its commitment to rapid proliferation and high rate of differentiation. Its morphological organization...

  1. Mammary Fat of Breast Cancer: Gene Expression Profiling and Functional Characterization

    Fengliang Wang; Sheng Gao; Fei Chen; Ziyi Fu; Hong Yin; Xun Lu; Jing Yu; Cheng Lu

    2014-01-01

    Mammary fat is the main composition of breast, and is the most probable candidate to affect tumor behavior because the fat produces hormones, growth factors and adipokines, a heterogeneous group of signaling molecules. Gene expression profiling and functional characterization of mammary fat in Chinese women has not been reported. Thus, we collected the mammary fat tissues adjacent to breast tumors from 60 subjects, among which 30 subjects had breast cancer and 30 had benign lesions. We isolat...

  2. Morphological and immunohistochemical assays of surgically removed mammary gland tumors in bitches

    Magaš Vladimir; Jović S.; Nešić V.; Bacetić D.; Aleksić-Kovačević Sanja

    2007-01-01

    In this study an estimation of the malignancy of mammary gland tumors was carried out based upon clinical examination, macroscopic and pathohistological characteristics of neoplasms and expression of cytokeratins. In the study 60 bitches of different ages, race and reproductive status with clinically evident signs of mammary gland tumor were included. After clinical examination the mammary gland tumors were excided, after which tissue samples were taken for subsequent pathohistological and im...

  3. Synergism of diethylstilbestrol and other carcinogens in concurrent development of hepatic, mammary, and pituitary tumors in castrated male rats

    Castrated male WF rats, given implants of pellets containing 5.0 mg diethylstilbestrol (DES), were given N-butyl-N-nitrosourea (NBU) in small amounts, which alone produced no mammary tumors in intact female rats. Treatment resulted in the high yield of hepatic tumors (HT), mammary tumors (MT), and pituitary tumors (PT) concurrently in each rat. If animals were further tested with prolactin, the development of HT and MT was accelerated, whereas that of PT was suppressed. None of the intact or castrated rats receiving NBU and/or prolactin developed tumors in any tissues if DES treatment was omitted. Exposure of male rats, preconditioned similarly to NBU treatment, to 200 rads of 14.1-MeV fast-neutron radiation also elicited HT, MT, and PT with an efficiency comparable to that of NBU-treated rats. These findings indicate that DES played an essential role in the whole carcinogenic process in each tissue and that castrated male rats, if conditioned properly with estrogens, are useful for the study of the carcinogenesis mechanism in these tissues

  4. Homeobox genes in mammary gland development and neoplasia

    Both normal development and neoplastic progression involve cellular transitions from one physiological state to another. Whereas much is being discovered about signal transduction networks involved in regulating these transitions, little progress has been made in identifying the higher order genetic determinants that establish and maintain mammary cell identity and dictate cell type-specific responses to mammotropic signals. Homeobox genes are a large superfamily of genes whose members function in establishing and maintaining cell fate and cell identity throughout embryonic development. Recent genetic and expression analyses strongly suggest that homeobox genes may perform similar functions at specific developmental transition points in the mammary gland. These analyses also suggest that homeobox genes may play a contributory or causal role in breast cancer

  5. Modeling and analysis of transport in the mammary glands

    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. (paper)

  6. Modeling and analysis of transport in the mammary glands

    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.

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

    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......-immunoreactivity was revealed homogeneously in the cytoplasm of the secretory cells, which might suggest that EGF is present as a precursor molecule in the mammary glands. Altered glucose metabolism during lactation results in secondary hypoinsulinaemia in the lactating rat. As insulin is also known to affect...... lactation in several species, we treated normal lactating rats daily with insulin and studied the effect on the composition of milk. A significant increase in the content of total protein and milk fat was observed after a few days of insulin-treatment, as compared to a control group [total protein: 50 (36...

  8. Intracellular behaviour of samarium and europium in lactating mammary gland

    Ayadi Ahlem; Maghraoui Samira; El Hili Ali; Galle Pierre; Tekaya Leila

    2012-01-01

    The subcellular localization of samarium and europium,two rare-earths,increasingly used in both medical and industrial fields,has been studied in several organs such as liver and kidney but never in the mammary gland despite of its importance in the biology of lactation and nutrition domains.The intracellular behaviour of samarium and europium after their intra-peritoneal administration in the lactating mammary gland cells was investigated.The results showed the presence of very electron dense deposits in the glandular epithelial cell lysosomes.These particular lysosomes were never observed in the marnrnary cell lysosomes of control rats.These intralysosomal deposits were probably composed of insoluble samarium or europium phosphates by analogy with previous studies,the transmission electron microscopy,the ion mass microscopy and the electron probe microanalysis,and other techniques allowing the identification of the chemical structure of the intralysosomal deposits.

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

    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. PMID:25435974

  10. Neuroendocrine carcinoma of the mammary gland in a dog.

    Nakahira, R; Michishita, M; Yoshimura, H; Hatakeyama, H; Takahashi, K

    2015-01-01

    A 10-year-old female border collie was presented with a mass (2 cm diameter) in the fifth mammary gland. The mass was located in the subcutis and the cut surface was grey-white in colour. Microscopically, the mass was composed of tumour cells arranged in nests of various sizes separated by delicate fibrovascular stroma. The tumour cells had small, round hypochromatic nuclei and abundant cytoplasm. Metastases were observed in the inguinal lymph node. Immunohistochemically, most tumour cells expressed cytokeratin (CK) 20, chromogranin A, neuron-specific enolase, synaptophysin and oestrogen receptor-β, but not low molecular weight CK (CAM5.2), p63 and insulin. Ultrastructurally, the tumour cells contained a large number of electron-dense granules corresponding to neuroendocrine granules. Based on these findings, this case was diagnosed as a neuroendocrine carcinoma of the mammary gland. PMID:25670668

  11. Low-calorie diet prevents the development of mammary tumors in C3H mice and reduces circulating prolactin level, murine mammary tumor virus expression, and proliferation of mammary alveolar cells

    Sarkar, Nurul H.; Fernandes, Gabriel; Telang, Nitin T.; Kourides, Ione A.; Good, Robert A.

    1982-01-01

    The effect of carlorie intake on the development of spontaneous mammary tumors in virgin C3H mice was studied. Only about 10% of the mice fed a low-calorie diet [10 kcal/day (1 kcal = 4.184 kJ)] since weaning developed mammary tumors, compared to about 60% of those mice that were reared on high-calorie diets (16 kcal/day or lab chow ad lib). In order to understand the mechanism by which a low-calorie diet decreases the occurrence of mammary tumors in mice, we compared the sex cycle, the amoun...

  12. MUON ACCELERATION

    BERG,S.J.

    2003-11-18

    One of the major motivations driving recent interest in FFAGs is their use for the cost-effective acceleration of muons. This paper summarizes the progress in this area that was achieved leading up to and at the FFAG workshop at KEK from July 7-12, 2003. Much of the relevant background and references are also given here, to give a context to the progress we have made.

  13. KEKB accelerator

    KEKB, the B-Factory at High Energy Accelerator Research Organization (KEK) recently achieved the luminosity of 1 x 1034 cm-2s-1. This luminosity is two orders higher than the world's level at 1990 when the design of KEKB started. This unprecedented result was made possible by KEKB's innovative design and technology in three aspects - beam focusing optics, high current storage, and beam - beam interaction. Now KEKB is leading the luminosity frontier of the colliders in the world. (author)

  14. Δn89β-Catenin Induces Precocious Development, Differentiation, and Neoplasia in Mammary Gland

    Imbert, Alexandra; Eelkema, Rachel; Jordan, Sara; Feiner, Helen; Cowin, Pamela

    2001-01-01

    To investigate the role of β-catenin in mammary gland development and neoplasia, we expressed a stabilized, transcriptionally active form of β-catenin lacking the NH2-terminal 89 amino acids (ΔN89β-catenin) under the control of the mouse mammary tumor virus long terminal repeat. Our results show that ΔN89β-catenin induces precocious lobuloalveolar development and differentiation in the mammary glands of both male and female mice. Virgin ΔN89β-catenin mammary glands resemble those found in wil...

  15. Expression profile of microRNAs in c-Myc induced mouse mammary tumors

    Sun, Yuan; Wu, Jack; Wu, Si-hung; Thakur, Archana; Bollig, Aliccia; Huang, Yong; Liao, D. Joshua

    2008-01-01

    c-Myc is a transcription factor overexpression of which induces mammary cancer in transgenic mice. To explore whether certain microRNAs (mirRNA) mediate c-Myc induced mammary carcinogenesis, we studied mir-RNA expression profile in mammary tumors developed from MMTV-c-myc transgenic mice, and found 50 and 59 mirRNAs showing increased and decreased expression, respectively, compared with lactating mammary glands of wild type mice. Twenty-four of these mirRNAs could be grouped into eight cluste...

  16. Transgenic Mammary Epithelial Osteopontin (Spp1) Expression Induces Proliferation and Alveologenesis

    Hubbard, Neil E; Chen, Qian J.; Sickafoose, Laura K.; Wood, Meghan B.; Gregg, Jeffrey P; Abrahamsson, Ninnie M.; Engelberg, Jesse A; Walls, Judith E; Borowsky, Alexander D.

    2013-01-01

    Osteopontin (OPN) Spp1 is involved in differentiation of the mammary gland. We engineered mice to overexpress OPN in mammary epithelium and describe an altered mammary phenotype. Three transgenic (Tg) founder lines FVB/N Tg(MMTV-Opn)(1-3BOR) were propagated after FVB/NJ pronuclear injections. Mammary glands from Tg-OPN mice compared to littermate controls showed, at 4 weeks of age, exaggerated terminal end buds; at 8 and 12 weeks, more numerous and complex ducts with increased luminal protein...

  17. A Novel Mechanism of Resistance to Mouse Mammary Tumor Virus Infection

    Golovkina, Tatyana V.

    2000-01-01

    Exogenous mouse mammary tumor virus (MMTV) is carried from the gut of suckling pups to the mammary glands by lymphocytes and induces mammary gland tumors. MMTV-induced tumor incidence in inbred mice of different strains ranges from 0 to as high as 100%. For example, mice of the C3H/HeN strain are highly susceptible, whereas mice of the I/LnJ strain are highly resistant. Of the different factors that together determine the susceptibility of mice to development of MMTV-induced mammary tumors, g...

  18. Anti-tumor effect of SLPI on mammary but not colon tumor growth.

    Amiano, Nicolás O; Costa, María J; Reiteri, R Macarena; Payés, Cristian; Guerrieri, Diego; Tateosian, Nancy L; Sánchez, Mercedes L; Maffia, Paulo C; Diament, Miriam; Karas, Romina; Orqueda, Andrés; Rizzo, Miguel; Alaniz, Laura; Mazzolini, Guillermo; Klein, Slobodanka; Sallenave, Jean-Michel; Chuluyan, H Eduardo

    2013-02-01

    Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor that was related to cancer development and metastasis dissemination on several types of tumors. However, it is not known the effect of SLPI on mammary and colon tumors. The aim of this study was to examine the effect of SLPI on mammary and colon tumor growth. The effect of SLPI was tested on in vitro cell apoptosis and in vivo tumor growth experiments. SLPI over-expressing human and murine mammary and colon tumor cells were generated by gene transfection. The administration of murine mammary tumor cells over-expressing high levels of SLPI did not develop tumors in mice. On the contrary, the administration of murine colon tumor cells over-expressing SLPI, developed faster tumors than control cells. Intratumoral, but not intraperitoneal administration of SLPI, delayed the growth of tumors and increased the survival of mammary but not colon tumor bearing mice. In vitro culture of mammary tumor cell lines treated with SLPI, and SLPI producer clones were more prone to apoptosis than control cells, mainly under serum deprivation culture conditions. Herein we demonstrated that SLPI induces the apoptosis of mammary tumor cells in vitro and decreases the mammary but not colon tumor growth in vivo. Therefore, SLPI may be a new potential therapeutic tool for certain tumors, such as mammary tumors. PMID:22767220

  19. Comparison of mouse mammary gland imaging techniques and applications: Reflectance confocal microscopy, GFP Imaging, and ultrasound

    Genetically engineered mouse models of mammary gland cancer enable the in vivo study of molecular mechanisms and signaling during development and cancer pathophysiology. However, traditional whole mount and histological imaging modalities are only applicable to non-viable tissue. We evaluated three techniques that can be quickly applied to living tissue for imaging normal and cancerous mammary gland: reflectance confocal microscopy, green fluorescent protein imaging, and ultrasound imaging. In the current study, reflectance confocal imaging offered the highest resolution and was used to optically section mammary ductal structures in the whole mammary gland. Glands remained viable in mammary gland whole organ culture when 1% acetic acid was used as a contrast agent. Our application of using green fluorescent protein expressing transgenic mice in our study allowed for whole mammary gland ductal structures imaging and enabled straightforward serial imaging of mammary gland ducts in whole organ culture to visualize the growth and differentiation process. Ultrasound imaging showed the lowest resolution. However, ultrasound was able to detect mammary preneoplastic lesions 0.2 mm in size and was used to follow cancer growth with serial imaging in living mice. In conclusion, each technique enabled serial imaging of living mammary tissue and visualization of growth and development, quickly and with minimal tissue preparation. The use of the higher resolution reflectance confocal and green fluorescent protein imaging techniques and lower resolution ultrasound were complementary

  20. Immunological characterization of a low oncogenic mouse mammary tumor virus BALB/cNIV mice.

    Vacquier, J P; Cardiff, R D; Blair, P B

    1981-01-01

    Antigenic determinants of mouse mammary tumor virus (MuMTV) from the low-mammary-tumor-incidence strain BALB/cNIV were compared by competition radioimmunoassay with those of MuMTV's isolated from several high- and low-mammary-tumor-incidence mouse strains, using rabbit hyperimmune sera against BALB/cNIV MuMTV and against MuMTV from the high-mammary-tumor-incidence strain BALB/cfC3H. Using anti-BALB/cfC3H serum in competition radioimmunoassay, BALB/cNIV MuMTV lacked antigenic determinants pres...

  1. Accelerating networks

    Evolving out-of-equilibrium networks have been under intense scrutiny recently. In many real-world settings the number of links added per new node is not constant but depends on the time at which the node is introduced in the system. This simple idea gives rise to the concept of accelerating networks, for which we review an existing definition and-after finding it somewhat constrictive-offer a new definition. The new definition provided here views network acceleration as a time dependent property of a given system as opposed to being a property of the specific algorithm applied to grow the network. The definition also covers both unweighted and weighted networks. As time-stamped network data becomes increasingly available, the proposed measures may be easily applied to such empirical datasets. As a simple case study we apply the concepts to study the evolution of three different instances of Wikipedia, namely, those in English, German, and Japanese, and find that the networks undergo different acceleration regimes in their evolution

  2. Role of JNK in mammary gland development and breast cancer

    Cellurale, Cristina; Girnius, Nomeda; Jiang, Feng; Cavanagh-Kyros, Julie; Lu, Shaolei; Garlick, David S.; Mercurio, Arthur M.; Davis, Roger J

    2011-01-01

    JNK signaling has been implicated in the developmental morphogenesis of epithelial organs. In this study we employed a compound deletion of the murine Jnk1 and Jnk2 genes in the mammary gland to evaluate the requirement for these ubiquitously expressed genes in breast development and tumorigenesis. JNK1/2 was not required for breast epithelial cell proliferation or motility. However, JNK1/2 deficiency caused increased branching morphogenesis and defects in the clearance of lumenal epithelial ...

  3. Clear cell mammary malignant myoepithelioma with abundant glycogens.

    Kuwabara, H.; Uda, H

    1997-01-01

    Malignant myoepithelioma (myoepithelial carcinoma) of the breast is extremely rare. A case is reported of a 46 year old female with clear cell mammary malignant myoepithelioma that, on histological examination, was glycogen abundant clear cell carcinoma. Immunohistochemically, the clear cells showed myoepithelial differentiation--that is, they were a smooth muscle actin and S100 protein positive. This case shows that glycogen abundant clear cell carcinoma is a variant of malignant myoepitheli...

  4. Three-dimensional culture models of mammary gland

    Campbell, Jonathan J.; Watson, Christine J

    2009-01-01

    The mammary gland is a complex tissue comprised of a branching network of ducts embedded within an adipocyte-rich stroma. The ductal epithelium is a bi-layer of luminal and myoepithelial cells, the latter being in contact with a basement membrane. During pregnancy, tertiary branching occurs and lobuloalveolar structures, which produce milk during lactation, form in response to hormonal and cytokine signals. Postlactational regression is characterized by extensive cell death and tissue remodel...

  5. Angiotropic metastatic malignant melanoma in a canine mammary gland

    Yang, Hai Jie; Lee, Eun-Mi; Kim, Ah-Young; Lee, Eun-Joo; Hong, Il-Hwa; Huh, Sung-Oh; Jeong, Kyu-Shik

    2011-01-01

    An eleven-year-old spayed female Yorkshire Terrier presented with a sublumbar mass and upon ultrasonographic examination, was revealed to have a mammary gland tumor. Black to reddish colored masses, located in the visceral peritoneum of the sublumbar region was observed on laparotomy with masectomy of the right side. In the laparotomy, we observed reddish masses multifocally located in the serosal membrane of the large intestine. Histopathologic examination of the intestinal and abdominal mas...

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

    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...

  7. Characterization of an epithelial cell line from bovine mammary gland.

    German, Tania; Barash, Itamar

    2002-05-01

    Elucidation of the bovine mammary gland's unique characteristics depends on obtaining an authentic cell line that will reproduce its function in vitro. Representative clones from bovine mammary cell populations, differing in their attachment capabilities, were cultured. L-1 cells showed strong attachment to the plate, whereas H-7 cells detached easily. Cultures established from these clones were nontumorigenic upon transplantation to an immunodeficient host; they exhibited the epithelial cell characteristics of positive cytokeratin but not smooth muscle actin staining. Both cell lines depended on fetal calf serum for proliferation. They exhibited distinct levels of differentiation on Matrigel in serum-free, insulin-supplemented medium on the basis of their organization and beta-lactoglobulin (BLG) secretion. H-7 cells organized into mammospheres, whereas L-1 cells arrested in a duct-like morphology. In both cell lines, prolactin activated phosphorylation of the signal transducer and activator of transcription, Stat5-a regulator of milk protein gene transcription, and of PHAS-I-an inhibitor of translation initiation in its nonphosphorylated form. De novo synthesis and secretion of BLG were detected in differentiated cultures: in L-1 cells, BLG was dependent on lactogenic hormones for maximal induction but was less stringently controlled than was beta-casein in the mouse CID-9 cell line. L-1 cells also encompassed a near-diploid chromosomal karyotype and may serve as a tool for studying functional characteristics of the bovine mammary gland. PMID:12418925

  8. Experimental manipulation of radiographic density in mouse mammary gland

    Extensive mammographic density in women is associated with increased risk for breast cancer. Mouse models provide a powerful approach to the study of human diseases, but there is currently no model that is suited to the study of mammographic density. We performed individual manipulations of the stromal, epithelial and matrix components of the mouse mammary gland and examined the alterations using in vivo and ex vivo radiology, whole mount staining and histology. Areas of density were generated that resembled densities in mammographic images of the human breast, and the nature of the imposed changes was confirmed at the cellular level. Furthermore, two genetic models, one deficient in epithelial structure (Pten conditional tissue specific knockout) and one with hyperplastic epithelium and mammary tumors (MMTV-PyMT), were used to examine radiographic density. Our data show the feasibility of altering and imaging mouse mammary gland radiographic density by experimental and genetic means, providing the first step toward modelling the biological processes that are responsible for mammographic density in the mouse

  9. Clinicopathologic evaluation of mammary Paget′s disease

    Meibodi Naser

    2008-01-01

    Full Text Available Mammary and extramammary Paget′s diseases are rare neoplasms of epidermis and mucosal epithelium. Due to their nonspecific and variable clinical view, they have differential diagnosis with eczema, melanoma, Bowen′s disease, etc. To the best of our knowledge, no such study has been performed in Iran regarding the prevalence, clinical aspects, underlying disease and pathological characteristics of these two diseases. In this study, we have evaluated the clinical and histopathological aspects of this disorder. Materials and Methods: In this retrospective study, all Paget′s biopsied samples referred to the Pathology Department of Imam-Reza hospital, Mashhad, since 1984 till 2004 were evaluated. Collected data were analyzed by descriptive statistical methods. Results: Among 98925 specimens, there were 29 cases of Paget′s disease. All cases were married women suffering from mammary Paget. The mean age was 53 ± 11 years. Left and right breast involvement was observed in 17 and 12 cases, all unilateral. The most common clinical view was ulcerated (27% and then erythematosus exudative plaques. More than 50% of patients were symptomatic. Most common symptoms were itching, pain and burning. The exclusive underlying pathological diagnosis was ductal carcinoma (55%. Discussion: In most cases, the clinical view of mammary Paget′s disease was helpful. Unilateral ulcerated plaque was the most common clinical sign. Majority of the accompanying pathology was ductal carcinoma. We had no cases of extramammary Paget′s disease in our study.

  10. Altered oxidant-antioxidant profile in canine mammary tumours.

    Kumaraguruparan, R; Balachandran, C; Manohar, B Murali; Nagini, S

    2005-05-01

    Mammary tumours are the most common neoplasms in female dogs. Oxidative stress arising due to overproduction of reactive oxygen species, coupled with altered antioxidant capacities has been implicated in the pathogenesis of all types of cancers. However, the extent of lipid peroxidation and the status of antioxidants in canine mammary tumours have not been investigated. The present study was designed to evaluate the oxidant-antioxidant profile in canine mammary tumours. Lipid peroxidation as evidenced by the formation of thiobarbituric acid-reactive substances, lipid hydroperoxides, and conjugated dienes, as well as the status of the antioxidants superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase, glutathione S-transferase and vitamin C, in tumour tissues of 25 bitches was estimated. Lipid peroxidation in tumour tissues was enhanced compared to the corresponding adjacent uninvolved tissues. This was accompanied by significant elevation in both enzymatic and non-enzymatic antioxidants. This study suggests that upregulation of antioxidants induced by lipid peroxidation confers a selective growth advantage to tumour cells over their adjacent normal counterparts. PMID:15751580

  11. Modern View of the Mammary Gland Cancer Local Recurrence Problem

    Poddubnaya I.V.

    2009-06-01

    Full Text Available The notions of local, regional and locoregional recurrences of the mammary gland cancer are singled out in modern literature. A confusion of the recurrence notions leads to difficulties not only in detection of their appearance rate and a clinicomorphological characteristic, but in assessment of the disease treatment and prognosis possibilities. The world data of the recurrence appearance clinicomorphological risk factors such as a primary tumor size, the regional lymph node lesion, the patient age, a presence of multiple centers and peritumoral tumor invasion, a use of postoperative radial therapy and etc. is systematized in the review. The data of the tumor receptor status and genetic factor role in development of the mammary gland local recurrences is presented. A clinicomorphological characteristic of the local recurrences considering a localization, number of tumoral nodes, a tumor shift, a presence of calcinates and such complications as a tumor ulceration or decomposition, a germination of neighboring structures and infection is given. The different types of the local recurrence treatment (surgical, medicinal, radial method and their combinations and a site of local recurrence in prognosis of disease in patients with a mammary gland cancer are studied.

  12. Unexpected severe consequences of Pikfyve deletion by aP2- or Aq-promoter-driven Cre expression for glucose homeostasis and mammary gland development.

    Ikonomov, Ognian C; Sbrissa, Diego; Delvecchio, Khortnal; A Rillema, James; Shisheva, Assia

    2016-06-01

    Systemic deficiency of PIKfyve, the evolutionarily conserved phosphoinositide kinase synthesizing cellular PtdIns5P and PtdIns(3,5)P2 and implicated in insulin signaling, causes early embryonic death in mice. In contrast, mice with muscle-specific Pikfyve disruption have normal lifespan but exhibit early-age whole-body glucose intolerance and muscle insulin resistance, thus establishing the key role of muscle PIKfyve in glucose homeostasis. Fat and muscle tissues control postprandial glucose clearance through different mechanisms, raising questions as to whether adipose Pikfyve disruption will also trigger whole-body metabolic abnormalities, and if so, what the mechanism might be. To clarify these issues, here we have characterized two new mouse models with adipose tissue disruption of Pikfyve through Cre recombinase expression driven by adipose-specific aP2- or adiponectin (Aq) promoters. Whereas both mouse lines were ostensibly normal until adulthood, their glucose homeostasis and systemic insulin sensitivity were severely dysregulated. These abnormalities stemmed in part from accelerated fat-cell lipolysis and elevated serum FFA Intriguingly, aP2-Cre-PIKfyve(fl/fl) but not Aq-Cre-PIKfyve(fl/fl) females had severely impaired pregnancy-induced mammary gland differentiation and lactogenesis, consistent with aP2-Cre-mediated Pikfyve excision in nonadipogenic tissues underlying this defect. Intriguingly, whereas mammary glands from postpartum control and Aq-Cre-PIKfyve(fl/fl) mice or ex vivo mammary gland explants showed profound upregulation of PIKfyve protein levels subsequent to prolactin receptor activation, such increases were not apparent in aP2-Cre-PIKfyve(fl/fl) females. Collectively, our data identify for the first time that adipose tissue Pikfyve plays a key role in the mechanisms regulating glucose homeostasis and that the PIKfyve pathway is critical in mammary epithelial differentiation during pregnancy and lactogenesis downstream of prolactin receptor

  13. The Mouse Mammary Tumor Virus Transcription Enhancers for Hematopoietic Progenitor and Mammary Gland Cells Share Functional Elements

    Reuss, Frank U.; Coffin, John M.

    2000-01-01

    Expression of mouse mammary tumor virus (MMTV)-encoded superantigens in B lymphocytes is required for viral transmission and pathogenesis. We have previously established a critical role of an enhancer element within the long terminal repeat (LTR) for MMTV sag gene expression in B-lymphoid progenitor cells. We now demonstrate enhancer activity of this element in a promyelocytic progenitor cell line. We also map the position of the enhancer within the U3 region of the MMTV LTR and show that the...

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

    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.

  15. Accelerators and the Accelerator Community

    Malamud, Ernest; Sessler, Andrew

    2008-06-01

    In this paper, standing back--looking from afar--and adopting a historical perspective, the field of accelerator science is examined. How it grew, what are the forces that made it what it is, where it is now, and what it is likely to be in the future are the subjects explored. Clearly, a great deal of personal opinion is invoked in this process.

  16. Association of cellular and molecular responses in the rat mammary gland to 17β-estradiol with susceptibility to mammary cancer

    We are using ACI and BN rats, which differ markedly in their susceptibility to 17β-estradiol (E2)-induced mammary cancer, to identify genetic variants and environmental factors that determine mammary cancer susceptibility. The objective of this study was to characterize the cellular and molecular responses to E2 in the mammary glands of ACI and BN rats to identify qualitative and quantitative phenotypes that associate with and/or may confer differences in susceptibility to mammary cancer. Female ACI and BN rats were treated with E2 for 1, 3 or 12 weeks. Mammary gland morphology and histology were examined by whole mount and hematoxylin and eosin (H&E) staining. Cell proliferation and epithelial density were evaluated by quantitative immunohistochemistry. Apoptosis was evaluated by quantitative western blotting and flow cytometry. Mammary gland differentiation was examined by immunohistochemistry. Gene expression was evaluated by microarray, qRT-PCR and quantitative western blotting assays. Extracellular matrix (ECM) associated collagen was evaluated by Picrosirius Red staining and Second Harmonic Generation (SHG) microscopy. The luminal epithelium of ACI rats exhibited a rapid and sustained proliferative response to E2. By contrast, the proliferative response exhibited by the mammary epithelium of BN rats was restrained and transitory. Moreover, the epithelium of BN rats appeared to undergo differentiation in response to E2, as evidenced by production of milk proteins as well as luminal ectasia and associated changes in the ECM. Marked differences in expression of genes that encode proteins with well-defined roles in mammary gland development (Pgr, Wnt4, Tnfsf11, Prlr, Stat5a, Areg, Gata3), differentiation and milk production (Lcn2, Spp1), regulation of extracellular environment (Mmp7, Mmp9), and cell-cell or cell-ECM interactions (Cd44, Cd24, Cd52) were observed. We propose that these cellular and molecular phenotypes are heritable and may underlie, at least in

  17. Binding of transcobalamin II by human mammary epithelial cells.

    Adkins, Y; Lönnerdal, B

    2001-01-01

    The presence of nutrient binders in milk may have an important role during milk production and may influence the nutrient's bioavailability to the infant. Human milk and plasma contain at least two types of vitamin B12 binders: transcobalamin II (TCII) and haptocorrin (Hc). Vitamin B12 in milk is exclusively bound to Hc (Hc-B12). In plasma, the major vitamin B12 binding protein that is responsible for delivering absorbed vitamin B12 to most tissues and cells is TCII (TCII-B12). Currently, little is known about the route of secretion of vitamin B12 into human milk. It is possible that a receptor-mediated pathway is involved, since maternal vitamin B12 supplementation increases the amount of the vitamin secreted into human milk if the mother's vitamin B12 consumption is low, but remains unchanged if her intake is adequate. In this study, we investigated the process by which the mammary gland acquires vitamin B12 from maternal circulation, whether as a free vitamin or as a Hc-B12 or TCII-B12 complex. TCII was purified from plasma incubated with [57Co]vit B12 (B12*), while Hc was purified from whey incubated with B12*. Both proteins were separated by fast protein liquid chromatography using gel filtration and anion-exchange columns. Purity of the separated proteins was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Binding studies were carried out on a monolayer of normal human mammary epithelial cells (HMEC) at 4 degrees C using free B12* and TCII-B12* and Hc-B12* complexes. Minimal binding of free B12* and Hc-B12* to HMEC was observed; however, HMEC exhibited a high affinity for the TCII-B12* complex. This study suggests that a specific cell surface receptor for the TCII-B12 complex exists in the mammary gland. It is possible that once vitamin B12 is in the mammary gland it is transferred to Hc (which may be synthesized by the mammary gland) and then secreted into milk as a Hc-B12 complex. PMID:11787717

  18. Identification and characterization of cancer initiating cells from BRCA1 related mammary tumors using markers for normal mammary stem cells

    Athanassios Vassilopoulos, Rui-Hong Wang, Constantinos Petrovas, David Ambrozak, Richard Koup, Chu-Xia Deng

    2008-01-01

    Full Text Available It is hypothesized that cancer stem cells arise either from normal stem cells or from progenitor cells that have gained the ability to self-renew. Here we determine whether mammary cancer stem cells can be isolated by using antibodies that have been used for the isolation of normal mammary stem cells. We show that BRCA1 mutant cancer cell lines contained a subpopulation of CD24+CD29+ or CD24+CD49f+ cells that exhibited increased proliferation and colony forming ability in vitro, and enhanced tumor-forming ability in vivo. The purified CD24+CD29+ cells could differentiate and reconstitute the heterogeneity found in parental cells when plated as a monolayer. Under low-attachment conditions, we detected “tumorspheres” only in the presence of double positive cells, which maintained their ability to self-renew. Furthermore, CD24+CD29+ cells could form tubular structures reminiscent of the mammary ductal tree when grown in three-dimensional cultures, implying that these cancer cells maintain some of the characteristics of the normal stem cells. Nevertheless, they could still drive tumor formation since as low as 500 double positive cells immediately after sorting from BRCA1 mutant primary tumors were able to form tumors with the same heterogeneity found in the original tumors. These data provide evidence that breast cancer stem cells originate from normal stem cells and advance our understanding of BRCA1-associated tumorigenesis with possible implications for future cancer treatment.

  19. accelerating cavity

    On the inside of the cavitytThere is a layer of niobium. Operating at 4.2 degrees above absolute zero, the niobium is superconducting and carries an accelerating field of 6 million volts per metre with negligible losses. Each cavity has a surface of 6 m2. The niobium layer is only 1.2 microns thick, ten times thinner than a hair. Such a large area had never been coated to such a high accuracy. A speck of dust could ruin the performance of the whole cavity so the work had to be done in an extremely clean environment.

  20. ABC- and SLC-Transporters in Murine and Bovine Mammary Epithelium - Effects of Prochloraz

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

    2016-01-01

    Some chemicals are ligands to efflux transporters which may result in high concentrations in milk. Limited knowledge is available on the influence of maternal exposure to chemicals on the expression and function of transporters in the lactating mammary gland. We determined gene expression of ABC and SLC transporters in murine mammary tissue of different gestation and lactation stages, in murine mammary cells (HC11) featuring resting and secreting phenotypes and in bovine mammary tissue and cells (BME-UV). Effects on transporter expression and function of the imidazole fungicide prochloraz, previously reported to influence BCRP in mammary cells, was investigated on transporter expression and function in the two cell lines. Transporters studied were BCRP, MDR1, MRP1, OATP1A5/OATP1A2, OCTN1 and OCT1. Gene expressions of BCRP and OCT1 in murine mammary glands were increased during gestation and lactation, whereas MDR1, MRP1, OATP1A5 and OCTN1 were decreased, compared to expressions in virgins. All transporters measured in mammary 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 and protein expression in both differentiated HC11 and BME-UV cells and increased protein function in HC11 cells, resulting in decreased accumulation of the MDR1 substrate digoxin. In conclusion, our results demonstrate that murine (HC11) and bovine (BME-UV) mammary epithelial cells can be applied to characterize expression and function of transporters as well as effects of contaminants on the mammary transporters. An altered expression, induced by a drug or toxic chemical, on any of the transporters expressed in the mammary epithelial cells during lactation may modulate the well-balanced composition of nutrients and/or secretion of contaminants in milk with potential adverse effects on breast-fed infants and dairy consumers. PMID:27028005

  1. Prolactin Suppression of Gonadotropin-Releasing Hormone Initiation of Mammary Gland Involution in Female Rats.

    Rieanrakwong, Duangjai; Laoharatchatathanin, Titaree; Terashima, Ryota; Yonezawa, Tomohiro; Kurusu, Shiro; Hasegawa, Yoshihisa; Kawaminami, Mitsumori

    2016-07-01

    It has been demonstrated that mammary gland involution after lactation is initiated by accumulation of milk in alveoli after weaning. Here, we report that involution is also dependent on mammary GnRH expression that is suppressed by PRL during lactation. Reduction of plasma prolactin (PRL) by the withdrawal of suckling stimuli increased GnRH and annexin A5 (ANXA5) expression in the mammary tissues after lactation with augmentation of epithelial apoptosis. Intramammary injection of a GnRH antagonist suppressed ANXA5 expression and apoptosis of epithelial cells after forcible weaning at midlactation, whereas local administration of GnRH agonist (GnRHa) caused apoptosis of epithelial cells with ANXA5 augmentation in lactating rats. The latter treatment also decreased mammary weight, milk production, and casein accumulation. Mammary mast cells were strongly immunopositive for GnRH and the number increased in the mammary tissues after weaning. GnRHa was shown to be a chemoattractant for mast cells by mammary local administration of GnRHa and Boyden chamber assay. PRL suppressed the mammary expression of both ANXA5 and GnRH mRNA. It also decreased mast cell numbers in the gland after lactation. These results are the first to demonstrate that GnRH, synthesized locally in the mammary tissues, is required for mammary involution after lactation. GnRH is also suggested to introduce mast cells into the regressing mammary gland and would be in favor of tissue remodeling. The suppression of these processes by PRL is a novel physiological function of PRL. PMID:27175971

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

    Fei Dong; Zhi-Bin Ji; Cun-Xian Chen; Gui-Zhi Wang; Jian-Min Wang

    2013-01-01

    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...

  3. Angiogenic responses elicited from chorioallantoic membrane vessels by neoplastic, preneoplastic, and normal mammary tissues from GR mice.

    Strum, J. M.

    1983-01-01

    Neoplastic tumors are able to elicit the ingrowth of new capillaries, a process known as angiogenesis. The chorioallantoic membrane (CAM) of chicken embryos was used in an assay for this response, and normal mammary glands and various mammary growths from GR mice, including plaques, hyperplasic alveolar nodules, and hormone-dependent and hormone-independent tumors were tested. Fifteen percent of the male mammary glands tested were positive, as were 28% of the resting female mammary glands. Fi...

  4. Rbpj conditional knockout reveals distinct functions of Notch4/Int3 in mammary gland development and tumorigenesis

    Raafat, A.; Lawson, S; Bargo, S; Klauzinska, M; Strizzi, L; Goldhar, AS; Buono, K; Salomon, D.; Vonderhaar, BK; Callahan, R

    2008-01-01

    Transgenic mice expressing the Notch 4 intracellular domain (ICD) (Int3) in the mammary gland have two phenotypes: arrest of mammary alveolar/lobular development and mammary tumorigenesis. Notch4 signaling is mediated primarily through the interaction of Int3 with the transcription repressor/activator Rbpj. We have conditionally ablated the Rbpj gene in the mammary glands of mice expressing whey acidic protein (Wap)-Int3. Interestingly, Rbpj knockout mice (Wap-Cre+/Rbpj−/−/ Wap-Int3) have nor...

  5. Long-term in vivo expression of genes introduced by retrovirus-mediated transfer into mammary epithelial cells.

    Smith, G. H.; Gallahan, D; Zwiebel, J A; Freeman, S M; Bassin, R H; Callahan, R

    1991-01-01

    Nonimmortalized mouse mammary epithelial cells expressing Escherichia coli beta-galactosidase from a murine amphotropic packaged retroviral vector were injected into the epithelium-divested mammary fat pads of syngeneic mice. Mammary glands formed from the injected mammary epithelial cells contained ductal and lobular cells, both of which expressed beta-galactosidase when examined in situ more than 12 months later. These results indicate that stable recombinant gene expression can be achieved...

  6. Intervention of T-cells in transportation of mouse mammary tumor virus (milk factor) to mammary gland cells in vivo.

    Tsubura, A; Inaba, M; Imai, S; Murakami, A; Oyaizu, N; Yasumizu, R; Ohnishi, Y; Tanaka, H; Morii, S; Ikehara, S

    1988-11-15

    Using BALB/c nu/nu, BALB/c nu/nufC3H (BALB/c nu/nu mice raised by C3H/HeN foster mother), BALB/c thymus-engrafted BALB/c nu/nufC3H, BALB/c nu/+, and BALB/c nu/+fC3H mice, we examined what kinds of cells are carriers of blood-borne mouse mammary tumor virus (B-MMTV). A radioimmunoassay and an immunoperoxidase assay revealed the presence of MMTV-gp52 antigen in the mammary glands of all BALB/c nu/+fC3H and BALB/c thymus-engrafted BALB/c nu/nufC3H mice (more than 60 days old) but only of some BALB/c nu/nufC3H mice (more than 120 days old): those that possessed a significant number of functional T-cells. BALB/c nu/+ mice did not show the antigen expression at any age. Transfer experiments of cells or plasma from young (less than 12 weeks) BALB/c nu/nufC3H to BALB/c +/+ virgins revealed that cells besides T-cells can also become carriers of B-MMTV. This was confirmed by Southern blotting analyses; exogenous provirus DNA sequences were found in B-cells as well as T-cells of BALB/c nu/+fC3H mice. However, when young BALB/c nu/nu mice were inoculated with BALB/c nu/nufC3H blood, they did not show the MMTV-gp52 antigen expression. Transfer experiments of purified T-cells, B-cells, natural killer cells, and macrophages from BALB/c fC3H mice to BALB/c nu/nu mice revealed that only T-cells have the ability to transfer viral activity to the mammary glands. These results suggest that B-MMTV is carried from the gastrointestinal tract to the mammary glands by lymphoid cells such as T-cells and B-cells, then transferred to the mammary gland cells by the T-cells. PMID:2846153

  7. Electron Accelerator Facilities

    Lecture presents main aspects of progress in development of industrial accelerators: adaptation of accelerators primary built for scientific experiments, electron energy and beam power increase in certain accelerator constructions, computer control system managing accelerator start-up, routine operation and technological process, maintenance (diagnostics), accelerator technology perfection (electrical efficiency, operation cost), compact and more efficient accelerator constructions, reliability improvement according to industrial standards, accelerators for MW power levels and accelerators tailored for specific use

  8. File list: InP.Brs.50.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available InP.Brs.50.AllAg.Mammary_stem_cells mm9 Input control Breast Mammary stem cells SRX...185841 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Brs.50.AllAg.Mammary_stem_cells.bed ...

  9. File list: NoD.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available NoD.Brs.10.AllAg.Mammary_stem_cells mm9 No description Breast Mammary stem cells ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Brs.10.AllAg.Mammary_stem_cells.bed ...

  10. File list: InP.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Full Text Available InP.Brs.05.AllAg.Mammary_stem_cells mm9 Input control Breast Mammary stem cells SRX...185841 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Brs.05.AllAg.Mammary_stem_cells.bed ...

  11. Id-1 is not expressed in the luminal epithelial cells of mammary glands

    The family of inhibitor of differentiation/DNA binding (Id) proteins is known to regulate development in several tissues. One member of this gene family, Id-1, has been implicated in mammary development and carcinogenesis. Mammary glands contain various cell types, among which the luminal epithelial cells are primarily targeted for proliferation, differentiation and carcinogenesis. Therefore, to assess the precise significance of Id-1 in mammary biology and carcinogenesis, we examined its cellular localization in vivo using immunohistochemistry. Extracts of whole mammary glands from wild type and Id-1 null mutant mice, and tissue sections from paraffin-embedded mouse mammary glands from various developmental stages and normal human breast were subjected to immunoblot and immunohistochemical analyses, respectively. In both these procedures, an anti-Id-1 rabbit polyclonal antibody was used for detection of Id-1. In immunoblot analyses, using whole mammary gland extracts, Id-1 was detected. In immunohistochemical analyses, however, Id-1 was not detected in the luminal epithelial cells of mammary glands during any stage of development, but it was detected in vascular endothelial cells. Id-1 is not expressed in the luminal epithelial cells of mammary glands

  12. A local basis for progesterone action during mammary tumorigenesis - no longer RANK and file

    Petrie, Whitney K; Hovey, Russell C

    2011-01-01

    Two recent reports provide compelling insights into the role for RANK and its ligand, RANKL, in progestin-dependent mammary tumorigenesis. These findings build upon a considerable body of evidence pointing to the RANK signaling pathway as being a key mediator of progestin action in the mammary glands.

  13. A hypothesis to relate salivary tumors with mammary and prostate neoplasias

    Actis, Adriana B

    2005-01-01

    Salivary, mammary and prostate glands are sex hormone-dependent organs sharing common aspects in structure, hormonal responsiveness and tumor histopathology. Salivary tumors (especially the malignant types) are not as frequent as mammary and prostate neoplasias. Hence, prognosis of some salivary tumors is not always efficient. Here, we review the oncology of salivary gland and its putative relation to breast/prostate tumors.

  14. Impact of let-7g on Proliferation and Lactation of Mouse Mammary Epithelial Cells

    Feng Li; Li Qing-zhang; Cui Wei; Ding Wei

    2012-01-01

    let-7g, a member of the let-7 family, regulates gene expression at the post-transcriptional level. The study explored a series of biological effects of mouse mammary epithelial cells that let-7g was produced. The differential expression of let-7g was detected by qRT-PCR in different developmental stages of the mouse mammary gland, let-7g expression and impact of let-7g on mouse mammary epithelial cells were analyzed by CASY-technology, qRT-PCR, Western blotting and HPLC inhibited let-7g expression of mouse mammary epithelial ceils through gene silencing. The results showed that qRT-PCR identified let-7g as being down-regulated in mouse mammary epithelial cells after it was inhibited. Mouse mammary epithelial cells with low expression of let-7g displayed higher expression of TGFβR I protein than those with high expression of let-7g, suggesting that low let-7g expression contributed to TGFβR I over-expression. Finally, the expression of let-7g was down-regulated, which significantly enhanced the proliferation of mouse mammary epithelial cells, and increased expression of β-Casein. The data indicated that let-7g could negatively regulate the expression of target Tgfbrl by complementary combination in mouse mammary epithelial cells, and then regulate the cell proliferation and expression of β-Casein by suppressing the TGFβR I expression.

  15. Increased expression of C5a receptor (CD88) mRNA in canine mammary tumors.

    Hezmee, Mohd Noor Mohd; Kyaw-Tanner, Myat; Lee, Jia Yu Peppermint; Shiels, Ian A; Rolfe, Barbara; Woodruff, Trent; Mills, Paul C

    2011-01-01

    Mammary tumors are among the most common neoplastic conditions in dogs, and there is evidence that inflammation plays a role in the development of some tumor types in dogs. The complement system is a major participant in the inflammatory process and the complement activation component, C5a, is a potent inflammatory peptide. This study investigated the mRNA expression of the major receptor for C5a (C5aR; CD88) in histopathological samples of canine mammary tumors by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) using canine-specific primers for CD88. A total of seven canine mammary tumors (four malignant carcinomas, two benign mixed mammary tumors, and one myoepithelioma) and eight normal mammary glands were analysed. All the tumor samples expressed low levels of CD88 mRNA, while none of the normal mammary tissues showed any detectable expression. These preliminary results suggest that C5a-CD88 interaction may play a contributory role in the inflammatory response associated with mammary tumor development in dogs. Further studies investigating the mechanisms behind complement activation and C5a receptor expression in canine mammary tumors are warranted. PMID:20846729

  16. Expression and function of leptin and its receptor in mouse mammary gland

    2007-01-01

    Leptin is an autocrine and paracrine factor which affects the development of duct, formation of gland alveolus, expression of milk protein gene and onset involution of mammary gland. In order to know the function and mechanism of leptin in mammary gland, the protein expression and localization of leptin and its long form receptor (OB-Rb) were detected by a confocal laser scanning microscope. To study the impacts of leptin on mammary gland and leptin signal transduction pathway in pregnancy-, lactation- and involution-stage mammary gland, explants were cultured and Western blotting was used. The results showed that in the whole development cycle of mammary gland, the expression of leptin and OB-Rb was in positive correlation. In virgin the leptin expression was the highest and then decreased in pregnancy. In lactation the expression of leptin was low and upgraded in involution, and recovered to the original level about virgin on involution 13 d. The localization of leptin and OB-Rb revealed that leptin induced the expression of OB-Rb specifically and controlled the development and physiological function of the mammary gland by binding to OB-Rb. In pregnancy stage, leptin stimulated proliferation and differentiation of ductal epithelial cells by JAK-MAPK signal pathway. In lactation, leptin induced gene expression of β-casein by JAK-STAT5 signal pathway, and in involution leptin induced mammary epithelial cell apoptosis and mammary gland restitution by JAK-STAT3 signal pathway.

  17. A Spectrum of Monoclonal Antibodies Reactive with Human Mammary Tumor Cells

    Colcher, D.; Horan Hand, P.; Nuti, M.; Schlom, J.

    1981-05-01

    Splenic lymphocytes of mice, immunized with membrane-enriched fractions of metastatic human mammary carcinoma tissues, were fused with the NS-1 non-immunoglobulin-secreting murine myeloma cell line. This resulted in the generation of hybridoma cultures secreting immunoglobulins reactive in solid-phase radioimmunoassays with extracts of metastatic mammary carcinoma cells from involved livers, but not with extracts of apparently normal human liver. As a result of further screening of immunoglobulin reactivities and double cloning of cultures, 11 monoclonal antibodies were chosen that demonstrated reactivities with human mammary tumor cells and not with apparently normal human tissues. These monoclonal antibodies could be placed into at least five major groups on the basis of their differential binding to the surface of various live human mammary tumor cells in culture, to extracts of mammary tumor tissues, or to tissue sections of mammary tumor cells studied by the immunoperoxidase technique. Whereas a spectrum of reactivities to mammary tumors was observed with the 11 monoclonal antibodies, no reactivity was observed to apparently normal cells of the following human tissues: breast, lymph node, lung, skin, testis, kidney, thymus, bone marrow, spleen, uterus, thyroid, intestine, liver, bladder, tonsils, stomach, prostate, and salivary gland. Several of the antibodies also demonstrated a ``pancarcinoma'' reactivity, showing binding to selected non-breast carcinomas. None of the monoclonal antibodies showed binding to purified ferritin or carcinoembryonic antigen. Monoclonal antibodies of all five major groups, however, demonstrated binding to human metastatic mammary carcinoma cells both in axillary lymph nodes and at distal sites.

  18. REGULATION OF GENE EXPRESSION IN THE BOVINE MAMMARY GLAND BY OVARIAN STEROIDS

    It is well established that estrogen is required for mammary epithelial cell proliferation and ductal development in the growing animal, and that lobuloalveolar development during gestation is dependent upon progesterone. Effects of these steroid hormones on gene expression in the mammary gland are ...

  19. Mammary stem cells: Novel markers and novel approaches to increase lactation efficiency

    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 r...

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

    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...

  1. Accelerator system and method of accelerating particles

    Wirz, Richard E. (Inventor)

    2010-01-01

    An accelerator system and method that utilize dust as the primary mass flux for generating thrust are provided. The accelerator system can include an accelerator capable of operating in a self-neutralizing mode and having a discharge chamber and at least one ionizer capable of charging dust particles. The system can also include a dust particle feeder that is capable of introducing the dust particles into the accelerator. By applying a pulsed positive and negative charge voltage to the accelerator, the charged dust particles can be accelerated thereby generating thrust and neutralizing the accelerator system.

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

    Líška, Ján; Brtko, Július; Dubovický, Michal; Macejová, Dana; Kissová, Viktória; Polák, Štefan; Ujházy, Eduard

    2016-02-14

    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

  3. PIGLETS’ GROWTH PERFORMANCE IN THE FIRST 3 DAYS OF LIFE IN CONNECTION WITH SUCKLED MAMMARY GLANDS

    H. SĂRĂNDAN

    2013-12-01

    Full Text Available The trial was carried out in the maternity of a pig commercial farm, on three sows with 9 piglets each, during the first 3 days of life of the latter. We monitored the piglets for 72 hours daily from the point of view of the number of feedings per mammary gland to quantify the degree of use and milk production in relation with the anatomical location of the mammary glands. We could see there are daily variations of the daily weight gain in relation to their body weight at birth, and that mammary glands were differently used, i.e. the number of feedings is higher in pectoral mammary glands. Mean milk production per feeding varied between 14.49 and 59.73 ml, depending on the anatomical position and on the number of secreting cells in the mammary glands.

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

    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.

  5. Internal mammary chain irradiation in breast cancer: State of the art

    Radiation therapy has a major role in the management of infiltrative breast cancers. However, there is no consensus for the prophylactic treatment of the internal mammary chain (IMC), with strategies that show strong differences according to centers and physicians. Indications for internal mammary chain radiotherapy are debated, since this treatment significantly increases the dose delivered to the heart and leads to potential technical difficulties. Important prospective data recently suggested that internal mammary chain radiotherapy would not be necessary, even in cases of internal or central tumor locations, or in patients with positive axillary lymph nodes. Although these data warrant confirmation by two other prospective trials, there is evidence that the indications for internal mammary chain radiotherapy should be careful and that high quality techniques should be used for decreasing the dose delivered to the heart. This review of literature presents the state of art on the radiotherapy of internal mammary chain, with special focus on the indications, techniques, and potential toxicity. (authors)

  6. Limb mammary syndrome: a new genetic disorder with mammary hypoplasia, ectrodactyly, and other Hand/Foot anomalies maps to human chromosome 3q27.

    Van Bokhoven, H.; Jung, M; Smits, A P; van Beersum, S.; Rüschendorf, F; Van Steensel, M; Veenstra, M; Tuerlings, J.H.; Mariman, E.C.; Brunner, H.G.; Wienker, T. F.; Reis, A.; Ropers, H H; Hamel, B C

    1999-01-01

    We report on a large Dutch family with a syndrome characterized by severe hand and/or foot anomalies, and hypoplasia/aplasia of the mammary gland and nipple. Less frequent findings include lacrimal-duct atresia, nail dysplasia, hypohydrosis, hypodontia, and cleft palate with or without bifid uvula. This combination of symptoms has not been reported previously, although there is overlap with the ulnar mammary syndrome (UMS) and with ectrodactyly, ectodermal dysplasia, and clefting syndrome. Al...

  7. Morinda citrifolia (Noni) Juice Augments Mammary Gland Differentiation and Reduces Mammary Tumor Growth in Mice Expressing the Unactivated c-erbB2 Transgene

    Witt-Enderby, Paula A.; Davis, Vicki L.; Foster, Warren G.; King, Tracy L.; Kotlarczyk, Mary P.; J. Mark Cline; Clafshenkel, William P.

    2012-01-01

    Morinda citrifolia (noni) is reported to have many beneficial properties, including on immune, inflammatory, quality of life, and cancer endpoints, but little is known about its ability to prevent or treat breast cancer. To test its anticancer potential, the effects of Tahitian Noni Juice (TNJ) on mammary carcinogenesis were examined in MMTV-neu transgenic mice. Mammary tumor latency, incidence, multiplicity, and metastatic incidence were unaffected by TNJ treatment, which suggests that it wo...

  8. Keratinocyte growth factor is a growth factor for mammary epithelium in vivo. The mammary epithelium of lactating rats is resistant to the proliferative action of keratinocyte growth factor.

    Ulich, T. R.; Yi, E. S.; Cardiff, R; Yin, S.; Bikhazi, N.; Biltz, R; Morris, C. F.; Pierce, G. F.

    1994-01-01

    Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family. KGF is secreted by stromal cells and affects epithelial but not mesenchymal cell proliferation. KGF injected intravenously was found to cause dramatic proliferation of mammary epithelium in the mammary glands of rats. KGF causes ductal neogenesis and intraductal epithelial hyperplasia but not lobular differentiation in nulliparous female rats. KGF causes ductal and lobular epithelial hyperplasia in male...

  9. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  10. Internal mammary artery aneurysm in Marfan syndrome: case report

    Marfan syndrome has a pleomorphic phenotype. Those affected have abnormalities in the eyes and in the nervous, cardiovascular and musculoskeletal systems. Among these abnormalities are many reported aneurysms, involving the ascending, descending thoracic and abdominal aorta, the sinus of Valsalva, and the internal carotid artery. We report a left internal mammary artery (LIMA) aneurysm in a patient with Marfan syndrome and no other known predisposition to such an aneurysm. No other case of LIMA aneurysm in Marfan syndrome has, to our knowledge, been reported. (author)

  11. Internal mammary artery aneurysm in Marfan syndrome: case report

    Common, A.A.; Pressacco, J.; Wilson, J.K. [Univ. of Toronto, Dept. of Mecial Imaging, Toronto, Ontario (Canada)

    1999-02-01

    Marfan syndrome has a pleomorphic phenotype. Those affected have abnormalities in the eyes and in the nervous, cardiovascular and musculoskeletal systems. Among these abnormalities are many reported aneurysms, involving the ascending, descending thoracic and abdominal aorta, the sinus of Valsalva, and the internal carotid artery. We report a left internal mammary artery (LIMA) aneurysm in a patient with Marfan syndrome and no other known predisposition to such an aneurysm. No other case of LIMA aneurysm in Marfan syndrome has, to our knowledge, been reported. (author)

  12. Signal Transducer and Activator of Transcription 5a Mediates Mammary Ductal Branching and Proliferation in the Nulliparous Mouse

    Santos, Sarah J.; Haslam, Sandra Z.; Conrad, Susan E.

    2010-01-01

    Signal transducer and activator of transcription (Stat)5a is a critical regulator of mammary gland development. Previous studies have focused on Stat5a's role in the late pregnant and lactating gland, and although active Stat5a is detectable in mammary epithelial cells in virgin mice, little is known about its role during early mammary gland development. In this report, we compare mammary gland morphology in pubertal and adult nulliparous wild-type and Stat5a−/− mice. The Stat5a-null mammary ...

  13. Tsc1 deficiency impairs mammary development in mice by suppression of AKT, nuclear ERα, and cell-cycle-driving proteins

    Zhenqi Qin; Hang Zheng; Ling Zhou; Yanhua Ou; Bin Huang; Bo Yan; Zhenshu Qin; Cuilan Yang; Yongchun Su; Xiaochun Bai; Jiasong Guo; Jun Lin

    2016-01-01

    Loss of Tsc1/Tsc2 results in excess cell growth that eventually forms hamartoma in multiple organs. Our study using a mouse model with Tsc1 conditionally knockout in mammary epithelium showed that Tsc1 deficiency impaired mammary development. Phosphorylated S6 was up-regulated in Tsc1 −/− mammary epithelium, which could be reversed by rapamycin, suggesting that mTORC1 was hyperactivated in Tsc1 −/− mammary epithelium. The mTORC1 inhibitor rapamycin restored the development of Tsc1 −/− mammary...

  14. Loss of sfrp1 promotes ductal branching in the murine mammary gland

    Gauger Kelly J

    2012-08-01

    Full Text Available Abstract Background Secreted frizzled-related proteins (SFRPs are a family of proteins that block the Wnt signaling pathway and loss of SFRP1 expression is found in breast cancer along with a multitude of other human cancers. Activated Wnt signaling leads to inappropriate mammary gland development and mammary tumorigenesis in mice. When SFRP1 is knocked down in immortalized non-malignant mammary epithelial cells, the cells exhibit a malignant phenotype which resembles the characteristics observed in metastatic breast cancer stem-like cells. However, the effects of SFRP1 loss on mammary gland development in vivo are yet to be elucidated. The work described here was initiated to investigate the role of SFRP1 in mammary gland development and whether SFRP1−/− mice exhibit changes in mammary gland morphology and cell signaling pathways shown to be associated with SFRP1 loss in vitro. Results 10 week old nulliparous SFRP1−/− mammary glands exhibited branching with clear lobulo-alveolar development, which normally only occurs in hormonally stimulated mid-pregnant wt mammary glands. Explant cultures of SFRP1−/− mammary glands display increased levels of a well known Wnt signaling target gene, Axin2. Histomorphologic evaluation of virgin glands revealed that by 10 weeks of age, the duct profile is markedly altered in SFRP1−/− mice showing a significantly higher density of ducts with distinct alveoli present throughout the mammary gland, and with focal ductal epithelial hyperplasia. These findings persist as the mice age and are evident at 23 weeks of age. Changes in gene expression, including c-Myc, TGFβ-2, Wnt4, RANKL, and Rspo2 early in mammary gland development are consistent with the excessive hyper branching phenotype. Finally, we found that loss of SFRP1 significantly increases the number of mammary epithelial cells capable of mammosphere formation. Conclusions Our study indicates that SFRP1 gene is critical for maintaining proper

  15. Relationship of Dose of Total-Body 60Co Radiation to Incidence of Mammary Neoplasia In Female Rats

    Female, Sprague-Dawley rats were exposed on the 40th day of age to a single dose of total-body 60Co gamma radiation. AH animals were studied for the presence of mammary neoplasia, for a 360-day period, by removing surgically each mammary tumor and subjecting each to histological examination. The overall survival rate was 96% and was not less than 94% in any group. Three of 75 control, non-exposed rats developed a total of 3 mammary neoplasms. Three of 54 rats exposed to 15.6 R developed 4 mammary neoplasms. Three of 54 rats exposed to 31.2 R developed 5 mammary neoplasms. Nine of 54 rats exposed to 62.5 R developed 13 mammary neoplasms. Eighteen of 54 rats exposed to 125 R developed 23 mammary neoplasms. Thirty-two of 54 rats exposed to 250 R developed 54 mammary neoplasms. Forty of 54 rats exposed to 500 R developed 105 mammary neoplasms. It appears that both the per cent of rats with mammary neoplasia and the total number of mammary neoplasms increases in a reasonably regular manner with increasing dose, when studied for one year post-exposure. These findings are in agreement with a previous report from this laboratory. (author)

  16. ApcMin, A Mutation in the Murine Apc Gene, Predisposes to Mammary Carcinomas and Focal Alveolar Hyperplasias

    Moser, Amy Rapaich; Mattes, Ellen M.; Dove, William F.; Lindstrom, Mary J.; Haag, Jill D.; Gould, Michael N.

    1993-10-01

    ApcMin (Min, multiple intestinal neoplasia) is a point mutation in the murine homolog of the APC gene. Min/+ mice develop multiple intestinal adenomas, as do humans carrying germ-line mutations in APC. Female mice carrying Min are also prone to develop mammary tumors. Min/+ mammary glands are more sensitive to chemical carcinogenesis than are +/+ mammary glands. Transplantation of mammary cells from Min/+ or +/+ donors into +/+ hosts demonstrates that the propensity to develop mammary tumors is intrinsic to the Min/+ mammary cells. Long-term grafts of Min/+ mammary glands also gave rise to focal alveolar hyperplasias, indicating that the presence of the Min mutation also has a role in the development of these lesions.

  17. Coexpression of exogenous and endogenous mouse mammary tumor virus RNA in vivo results in viral recombination and broadens the virus host range.

    Golovkina, T V; Jaffe, A B; Ross, S R

    1994-01-01

    Mouse mammary tumor virus is a replication-competent B-type murine retrovirus responsible for mammary gland tumorigenesis in some strains of laboratory mice. Mouse mammary tumor virus is transmitted horizontally through the milk (exogenous or milk-borne virus) to susceptible offspring or vertically through the germ line (endogenous provirus). Exogenously acquired and some endogenous mouse mammary tumor viruses are expressed at high levels in lactating mammary glands. We show here that there i...

  18. Fractal dimensionality analysis of normal and cancerous mammary gland thermograms

    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). Thermograms were obtained using electronic contact thermography. Significant differences in the Hurst exponent readings for the MT and the NT were observed when comparing the following: 1.The right NT (H = 0.40 ± 0.13) (mean ± standard deviation) and the right MT (H = 0.36 ± 0.10) (p = 0.037) (p – significance level). 2.The left NT (H = 0.40 ± 0.14) and the left MT (H = 0.37 ± 0.11) (p = 0.035). Given these differences, we conclude that the Hurst exponent computed with the aforementioned algorithm may be used in thermogram processing for the early diagnosis of mammary gland cancer.

  19. Mammary cancer in man: analysis of 22 cases

    22 cases of male patients,averaging 63 years of age(ranging 50-80)were diagnosed as mammary cancer carriers. None of them presented a clear risk factor. Three of them had family history of mammary cancer in females. The clinical presentation was 27.2% E I, 27,2% E II, 30% E III and 13% E IV. In most cases consulting was late, with an average delay of 10 months.Pathology corresponded an infiltrating ductal form in 19 cases, non-infiltrating ductal form in 2 cases and ductal in situ non infiltrating form in 1 case. Dosification of hormonal receptor was not carried out in any of these patients. Regional treatment consisted in surgery plus radiotherapy. Modified radical mastectomy predominated in 12 cases,mastectomy in 6 cases and cuadrantectomy in 2 cases. Two cases were considered non surgical. Techniques and dadiatin doses were conventional. Systemic treatments consisted in tamoxifen o or poli chemotherapy CMF type in 'adyuvancia' cases and tamoxifen o of poli chemotherapy FAC type in the metastatic forms. It was concluded that there is a need of hysthological confirmation of this type of tumor as well as the compulsory dosification of hormonal receptors in order to determine the therapeutic strategy

  20. Molecular based subtyping of feline mammary carcinomas and clinicopathological characterization.

    Soares, Maria; Madeira, Sara; Correia, Jorge; Peleteiro, Maria; Cardoso, Fátima; Ferreira, Fernando

    2016-06-01

    Molecular classification of feline mammary carcinomas (FMC) from which specific behavioral patterns may be estimated has potential applications in veterinary clinical practice and in comparative oncology. In this perspective, the main goal of this study was to characterize both the clinical and the pathological features of the different molecular phenotypes found in a population of FMC (n = 102), using the broadly accepted IHC-based classification established by St. Gallen International Expert Consensus panel. The luminal B/HER2-negative subtype was the most common (29.4%, 30/102) followed by luminal B/HER2-positive subtype (19.6%, 20/102), triple negative basal-like (16.7%, 17/102), luminal A (14.7%, 15/102), triple negative normal-like (12.7%, 13/102) and finally, HER2-positive subtype (6.9%, 7/102). Luminal A subtype was significantly associated with smaller tumors (p = 0.024) and with well differentiated ones (p feline mammary tumors and human breast cancer, reveal that feline can be a valuable model for comparative studies. PMID:27212699

  1. Regulatory roles of Oct proteins in the mammary gland.

    Qian, Xi; Zhao, Feng-Qi

    2016-06-01

    The expression of Oct-1 and -2 and their binding to the octamer motif in the mammary gland are developmentally and hormonally regulated, consistent with the expression of milk proteins. Both of these transcription factors constitutively bind to the proximal promoter of the milk protein gene β-casein and might be involved in the inhibition or activation of promoter activity via interactions with other transcription factors or cofactors at different developmental stages. In particular, the lactogenic hormone prolactin and glucocorticoids induce Oct-1 and Oct-2 binding and interaction with both the signal transducer and activator of transcription 5 (STAT5) and the glucocorticoid receptor on the β-casein promoter to activate β-casein expression. In addition, increasing evidence has shown the involvement of another Oct factor, Oct-3/4, in mammary tumorigenesis, making Oct-3/4 an emerging prognostic marker of breast cancer and a molecular target for the gene-directed therapeutic intervention, prevention and treatment of breast cancer. This article is part of a Special Issue entitled: The Oct Transcription Factor Family, edited by Dr. Dean Tantin. PMID:27044595

  2. Nuclear repartitioning of galectin-1 by an extracellular glycan switch regulates mammary morphogenesis.

    Bhat, Ramray; Belardi, Brian; Mori, Hidetoshi; Kuo, Peiwen; Tam, Andrew; Hines, William C; Le, Quynh-Thu; Bertozzi, Carolyn R; Bissell, Mina J

    2016-08-16

    Branching morphogenesis in the mammary gland is achieved by the migration of epithelial cells through a microenvironment consisting of stromal cells and extracellular matrix (ECM). Here we show that galectin-1 (Gal-1), an endogenous lectin that recognizes glycans bearing N-acetyllactosamine (LacNAc) epitopes, induces branching migration of mammary epithelia in vivo, ex vivo, and in 3D organotypic cultures. Surprisingly, Gal-1's effects on mammary patterning were independent of its glycan-binding ability and instead required localization within the nuclei of mammary epithelia. Nuclear translocation of Gal-1, in turn, was regulated by discrete cell-surface glycans restricted to the front of the mammary end buds. Specifically, α2,6-sialylation of terminal LacNAc residues in the end buds masked Gal-1 ligands, thereby liberating the protein for nuclear translocation. Within mammary epithelia, Gal-1 localized within nuclear Gemini bodies and drove epithelial invasiveness. Conversely, unsialylated LacNAc glycans, enriched in the epithelial ducts, sequestered Gal-1 in the extracellular environment, ultimately attenuating invasive potential. We also found that malignant breast cells possess higher levels of nuclear Gal-1 and α2,6-SA and lower levels of LacNAc than nonmalignant cells in culture and in vivo and that nuclear localization of Gal-1 promotes a transformed phenotype. Our findings suggest that differential glycosylation at the level of tissue microanatomy regulates the nuclear function of Gal-1 in the context of mammary gland morphogenesis and in cancer progression. PMID:27496330

  3. Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments

    Women who have undergone a full-term pregnancy before the age of 20 have one-half the risk of developing breast cancer compared with women who have never gone through a full-term pregnancy. This protective effect is observed universally among women of all ethnic groups. Parity in rats and mice also protects them against chemically induced mammary carcinogenesis. Seven-week-old virgin Lewis rats were given N-methyl-N-nitrosourea. Two weeks later the rats were treated with natural or synthetic estrogens and progestins for 7–21 days by subcutaneous implantation of silastic capsules. In our current experiment, we demonstrate that short-term sustained exposure to natural or synthetic estrogens along with progestins is effective in preventing mammary carcinogenesis in rats. Treatment with 30 mg estriol plus 30 mg progesterone for 3 weeks significantly reduced the incidence of mammary cancer. Short-term exposure to ethynyl estradiol plus megesterol acetate or norethindrone was effective in decreasing the incidence of mammary cancers. Tamoxifen plus progesterone treatment for 3 weeks was able to confer only a transient protection from mammary carcinogenesis, while 2-methoxy estradiol plus progesterone was effective in conferring protection against mammary cancers. The data obtained in the present study demonstrate that, in nulliparous rats, long-term protection against mammary carcinogenesis can be achieved by short-term treatments with natural or synthetic estrogen and progesterone combinations

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

    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.

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

    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.

  6. Lgr5-expressing cells are sufficient and necessary for postnatal mammary gland organogenesis.

    Plaks, Vicki; Brenot, Audrey; Lawson, Devon A; Linnemann, Jelena R; Van Kappel, Eline C; Wong, Karren C; de Sauvage, Frederic; Klein, Ophir D; Werb, Zena

    2013-01-31

    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. PMID:23352663

  7. Mammary fat of breast cancer: gene expression profiling and functional characterization.

    Fengliang Wang

    Full Text Available Mammary fat is the main composition of breast, and is the most probable candidate to affect tumor behavior because the fat produces hormones, growth factors and adipokines, a heterogeneous group of signaling molecules. Gene expression profiling and functional characterization of mammary fat in Chinese women has not been reported. Thus, we collected the mammary fat tissues adjacent to breast tumors from 60 subjects, among which 30 subjects had breast cancer and 30 had benign lesions. We isolated and cultured the stromal vascular cell fraction from mammary fat. The expression of genes related to adipose function (including adipogenesis and secretion was detected at both the tissue and the cellular level. We also studied mammary fat browning. The results indicated that fat tissue close to malignant and benign lesions exhibited distinctive gene expression profiles and functional characteristics. Although the mammary fat of breast tumors atrophied, it secreted tumor growth stimulatory factors. Browning of mammary fat was observed and browning activity of fat close to malignant breast tumors was greater than that close to benign lesions. Understanding the diversity between these two fat depots may possibly help us improve our understanding of breast cancer pathogenesis and find the key to unlock new anticancer therapies.

  8. Enrichment for Repopulating Cells and Identification of Differentiation Markers in the Bovine Mammary Gland.

    Rauner, Gat; Barash, Itamar

    2016-06-01

    Elucidating cell hierarchy in the mammary gland is fundamental for understanding the mechanisms governing its normal development and malignant transformation. There is relatively little information on cell hierarchy in the bovine mammary gland, despite its agricultural potential and relevance to breast cancer research. Challenges in bovine-to-mouse xenotransplantation and difficulties obtaining bovine-compatible antibodies hinder the study of mammary stem-cell dynamics in this species. In-vitro indications of distinct bovine mammary epithelial cell populations, sorted according to CD24 and CD49f expression, have been provided. Here, we successfully transplanted these bovine populations into the cleared fat pads of immunocompromised mice, providing in-vivo evidence for the multipotency and self-renewal capabilities of cells that are at the top of the cell hierarchy (termed mammary repopulating units). Additional outgrowths from transplantation, composed exclusively of myoepithelial cells, were indicative of unipotent basal stem cells or committed progenitors. Sorting luminal cells according to E-cadherin revealed three distinct populations: luminal progenitors, and early- and late-differentiating cells. Finally, miR-200c expression was negatively correlated with differentiation levels in both the luminal and basal branches of the bovine mammary cell hierarchy. Together, these experiments provide further evidence for the presence of a regenerative entity in the bovine mammary gland and for the multistage differentiation process within the luminal lineage. PMID:26615610

  9. From genes to milk: genomic organization and epigenetic regulation of the mammary transcriptome.

    Danielle G Lemay

    Full Text Available Even in genomes lacking operons, a gene's position in the genome influences its potential for expression. The mechanisms by which adjacent genes are co-expressed are still not completely understood. Using lactation and the mammary gland as a model system, we explore the hypothesis that chromatin state contributes to the co-regulation of gene neighborhoods. The mammary gland represents a unique evolutionary model, due to its recent appearance, in the context of vertebrate genomes. An understanding of how the mammary gland is regulated to produce milk is also of biomedical and agricultural importance for human lactation and dairying. Here, we integrate epigenomic and transcriptomic data to develop a comprehensive regulatory model. Neighborhoods of mammary-expressed genes were determined using expression data derived from pregnant and lactating mice and a neighborhood scoring tool, G-NEST. Regions of open and closed chromatin were identified by ChIP-Seq of histone modifications H3K36me3, H3K4me2, and H3K27me3 in the mouse mammary gland and liver tissue during lactation. We found that neighborhoods of genes in regions of uniquely active chromatin in the lactating mammary gland, compared with liver tissue, were extremely rare. Rather, genes in most neighborhoods were suppressed during lactation as reflected in their expression levels and their location in regions of silenced chromatin. Chromatin silencing was largely shared between the liver and mammary gland during lactation, and what distinguished the mammary gland was mainly a small tissue-specific repertoire of isolated, expressed genes. These findings suggest that an advantage of the neighborhood organization is in the collective repression of groups of genes via a shared mechanism of chromatin repression. Genes essential to the mammary gland's uniqueness are isolated from neighbors, and likely have less tolerance for variation in expression, properties they share with genes responsible for an

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

    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. PMID:24141782

  11. Effect of ionizing radiation on nitric oxide production in mouse mammary epithelial cells

    Full text: Nitric oxide (NO) is an important biological molecule with a wide variety of functions in physiological and pathophysiological events. We reported previously the presence of nitric oxide synthase (NOS) isoforms such as inducible, endothelial and neuronal types in the rat mammary glands. In addition, we demonstrated that a selective inhibitor of inducible NOS and NO-specific scavenger prevent radiation-induced rat mammary tumors, and that radiation-induced NO might contribute to tumor initiation of mammary glands in rat. However, the production and action of NO in the epithelium of mammary glands after the exposure of radiation are still unclear. In this current study we, therefore, examined the effects of ionizing radiation on a mouse mammary epithelial cell line (HC11) to provide a concrete evidence regarding the production of NO in the mammary epithelial cells after irradiation. The HC11 cells, established from COMMA-1D mouse mammary epithelial cell line, were cultured in RPMI-1640 growth medium containing 10% FCS, EGF and insulin until become confluence, then irradiated by X-ray with a dose at 10 or 30 Gy (1 Gy/min). After the irradiation, NO produced and secreted by HC11 cells into culture medium was estimated by the measurement of nitrite concentration in the culture medium with a Griess assay. HC11 cells produced NO spontaneously, and NO concentration was gradually increased during the experimented period. On the other hand, NO production was transiently enhanced immediately after irradiation of the cells in a dose-dependent manner. It, then, descended in an hour after irradiation, and returned to a basal level in 24 hours. These indicate that NO production was undoubtedly increased by irradiation in mammary epithelial cells, and support our previous propose that radiation-induced NO might contribute to initiation of tumorigenesis of mammary glands

  12. ELEVATED TRANS-MAMMARY TRANSMISSION OF Toxocara canis LARVAE IN BALB/c MICE

    Paula de Lima Telmo

    2015-02-01

    Full Text Available Toxocariasis is a widespread zoonosis and is considered an important worldwide public health problem. The aim of this study was to investigate the frequency of trans-mammary Toxocara canis infection in newborn BALB/c mice nursed by females experimentally infected with 1,200 eggs after delivery. After 50 days of age, the presence of larvae in different organs of the offspring was investigated. Trans-mammary infection was confirmed in 73.9% of the mice that had been nursed by infected females. These data show a high trans-mammary transmission of T. canis and confirm the significance of this transmission route in paratenic hosts.

  13. Conjugated Linoleic Acid Induces Mast Cell Recruitment during Mouse Mammary Gland Stromal Remodeling12

    Russell, Joshua S.; McGee, Sibel Oflazoglu; Ip, Margot M.; Kuhlmann, Dietrich; Masso-Welch, Patricia A.

    2007-01-01

    Conjugated linoleic acid (CLA) is a dietary chemopreventive agent that induces apoptosis in the mammary adipose vascular endothelium and decreases mammary brown adipose tissue (BAT) and white adipose tissue (WAT). To determine onset and extent of stromal remodeling, we fed CD2F1/Cr mice diets supplemented with 1 or 2 g/100 g mixed CLA isomers for 1–7 wk. BAT loss, collagen deposition, and leukocyte recruitment occurred in the mouse mammary fat pad, coincident with an increase in parenchymal-a...

  14. Epithelial Cell Differentiation Regulated by MicroRNA-200a in Mammary Glands

    NAGAOKA, Kentaro; Zhang, Haolin; Watanabe, Gen; Taya, Kazuyoshi

    2013-01-01

    Mammary gland epithelial cells undergo periodic cycles of proliferation, differentiation, and involution. Many studies have reported that miRNAs, which are small, non-coding RNAs, influence a variety of biological processes during posttranscriptional regulation. Here, we found that one miRNA, miR-200a, was relatively highly expressed in epithelial cell-rich organs such as mammary glands, lung, and kidney in mice. In mammary glands, miR-200a expression increased during mid-pregnancy through la...

  15. Expression pattern of mouse mammary tumor virus in transgenic mice carrying exogenous proviruses of different origins.

    Rollini, P; Billotte, J; Kolb, E.; Diggelmann, H.

    1992-01-01

    To study the tissue specificity of mouse mammary tumor virus (MMTV) gene expression, we developed two series of transgenic mice, containing the MMTV proviral DNA of mammary (GR) and kidney (C3H-K) origin. The expression pattern in the MMTV(GR) transgenic mice is very similar to that observed in infected animals, e.g., a strong preference for viral expression in the lactating mammary glands and lower levels of expression in salivary glands, lymphoid tissues, and male reproductive organs. One l...

  16. Scintillation Studies of the Mouse Mammary Tumor Virus with ^125I

    Yazdi, Amir; Blue, Eric; Bradley, Eric; Majewski, Stan; Mohammed, Shira; Qian, Jianguo; Saha, Margaret; Schworer, Stephen; Sutton, Jonathan; Weisenberger, Andrew; Welsh, Robert

    2007-10-01

    We have applied the techniques of scintillation imaging to studies of the mouse mammary tumor virus (MMTV). In these studies, Sodium Iodide Symporter (NIS) transfers the radioactive ^125I to the mammary glands of lactating mice and in particular to those mammaries with visible tumors. These studies have principally been carried out using pixellated scintillators coupled to position sensitive photomultiplier tubes (PSPMTs). More recently, we have initiated such studies with a monolithic slab of LaBr3 scintillator coupled to an array of PSPMTs. Several techniques of mapping and measuring the development of such tumors have been employed. These will be discussed in detail and preliminary results will be reported.

  17. Atm-haploinsufficiency enhances susceptibility to carcinogen-induced mammary tumors.

    Lu, Shu; Shen, Kate; Wang, Yaolin; Santner, Steven J.; Chen, Jie; Brooks, S. C.; Wang, Y. Alan

    2006-01-01

    Biomarkers of exposure & effect:: validationBiomarker: A-T carriersExposure/effect represented: DMBAStudy type (in vitro, animals, humans): Atm male miceMode of exposure (if in vivo) (acute, chronic, root of exposure): administration by oral gavageMethod of analysis: PCRDose-response: Nearly twice as many Atm heterozygotes developed mammary tumors (64.7%) as the wild-type mice (37.5%). RR for DMBA-induced mammary tumors is 1.7 for Atm heterozygotesAtm heterozygotes developed mammary tumors wi...

  18. Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein

    Humans are exposed to an array of both harmful and beneficial hormonally active compounds in the environment and through diet. Two such chemicals are Bisphenol A (BPA), a plasticizer, and genistein, a component of soy. Prepubertal exposure to BPA increased mammary carcinogenesis, while genistein suppressed cancer in a chemically-induced model of rodent mammary cancer. The purpose of this research was to determine the effects of combinational exposure to genistein and BPA on cell proliferation, apoptosis, and associated proteins as markers of cancer in mammary glands of rats exposed prepubertally to these environmental chemicals. Prepubertal rats (postpartum days (PND) 2–20) were exposed through lactation via nursing dams treated orally with sesame oil (SO), BPA, genistein, or a combination of BPA and genistein (BPA + Gen). Cell proliferation, apoptosis and protein expressions were investigated for mechanistic studies in mammary glands of rats exposed to these environmental chemicals. Prepubertal exposure to genistein increased cell proliferation in mammary glands of PND21 rats, while BPA increased cell proliferation in adult (PND50) rats. Prepubertal combinational exposure to BPA + Gen increased cell proliferation and reduced apoptosis in PND21 rats, but reduced cell proliferation and increased apoptosis in PND50 rats. The altered mechanisms behind these cellular responses appear to be centered on differential protein expression of caspases, PARP, Bad, p21, Akts, PTEN, ER-β and SRCs 1–3, in the rat mammary gland. Prepubertal BPA exposure resulted in increased cell proliferation in mammary glands of PND50 rats, a process associated with increased risk of cancer development in a chemically-induced mammary cancer. On the other hand, genistein stimulated cell proliferation at PND21, a process that correlates with mammary gland maturation and chemoprevention. In contrast to single chemical exposure, combinational exposure to BPA + Gen performed most similarly to

  19. Molecular mechanisms involved in casein gene expression and secretion in mouse mammary epithelial cells

    Mouse mammary epithelial cells (MMEC) secrete a group of milk-specific proteins including various caseins and whey proteins. Dissociated mammary epithelial cells maintain expression of most of their differentiated functions only if cells are plated on a suitable substratum. Casein production and section, cell morphology, and production of α-lactalbumin have been used as markers to assess the degree of differentiation of mammary cells in culture. The general consensus is that cells express their differentiated properties at high levels and for longer periods of time on such substrata. In this paper, the authors demonstrate that modulation of the expression of caseins by floating collagen gels is manifested at several regulatory points

  20. Surgical management for large chest keloids with internal mammary artery perforator flap.

    Xue, Dan; Qian, Huan

    2016-01-01

    Therapy for large symptomatic keloids is often plagued with complicated reconstruction manner and recurrence. This article reports a rare treatment combination for a chest keloid with internal mammary artery perforator flap reconstruction and radiation therapy. We excised the keloid and covered the defect with an internal mammary artery perforator flap. Immediate electron-beam irradiation therapy was applied on the second postoperative day. There was no sign of recurrence over the follow-up period of 18 months. The combination of internal mammary artery perforator flap and immediate radiation therapy is useful when faced with chest keloids of similar magnitude and intractability. PMID:26982790

  1. Emerging evidence of the physiological role of hypoxia in mammary development and lactation

    Yong Shao; Feng-Qi Zhao

    2014-01-01

    Hypoxia is a physiological or pathological condition of a deficiency of oxygen supply in the body as a whole or within a tissue. During hypoxia, tissues undergo a series of physiological responses to defend themselves against a low oxygen supply, including increased angiogenesis, erythropoiesis, and glucose uptake. The effects of hypoxia are mainly mediated by hypoxia-inducible factor 1 (HIF-1), which is a heterodimeric transcription factor consisting ofαandβsubunits. HIF-1βis constantly expressed, whereas HIF-1αis degraded under normal oxygen conditions. Hypoxia stabilizes HIF-1αand the HIF complex, and HIF then translocates into the nucleus to initiate the expression of target genes. Hypoxia has been extensively studied for its role in promoting tumor progression, and emerging evidence also indicates that hypoxia may play important roles in physiological processes, including mammary development and lactation. The mammary gland exhibits an increasing metabolic rate from pregnancy to lactation to support mammary growth, lactogenesis, and lactation. This process requires increasing amounts of oxygen consumption and results in localized chronic hypoxia as confirmed by the binding of the hypoxia marker pimonidazole HCl in mouse mammary gland. We hypothesized that this hypoxic condition promotes mammary development and lactation, a hypothesis that is supported by the following several lines of evidence:i) Mice with an HIF-1αdeletion selective for the mammary gland have impaired mammary differentiation and lipid secretion, resulting in lactation failure and striking changes in milk compositions;ii) We recently observed that hypoxia significantly induces HIF-1α-dependent glucose uptake and GLUT1 expression in mammary epithelial cells, which may be responsible for the dramatic increases in glucose uptake and GLUT1 expression in the mammary gland during the transition period from late pregnancy to early lactation;and ii ) Hypoxia and HIF-1αincrease the

  2. Pulsed DC accelerator for laser wakefield accelerator

    For the acceleration of ultra-short, high-brightness electron bunches, a pulsed DC accelerator was constructed. The pulser produced megavolt pulses of 1 ns duration in a vacuum diode. Results are presented from field emission of electrons in the diode. The results indicate that the accelerating gradient in the diode is approximately 1.5 GV/m

  3. Mifepristone inhibits MPA-and FGF2-induced mammary tumor growth but not FGF2-induced mammary hyperplasia

    Juan P. Cerliani

    2010-12-01

    Full Text Available We have previously demonstrated a crosstalk between fibroblast growth factor 2 (FGF2 and progestins inducing experimental breast cancer growth. The aim of the present study was to compare the effects of FGF2 and of medroxyprogesterone acetate (MPA on the mouse mammary glands and to investigate whether the antiprogestin RU486 was able to reverse the MPA- or FGF2-induced effects on both, mammary gland and tumor growth. We demonstrate that FGF2 administered locally induced an intraductal hyperplasia that was not reverted by RU486, suggesting that FGF2-induced effects are progesterone receptor (PR-independent. However, MPA-induced paraductal hyperplasia was reverted by RU486 and a partial agonistic effect was observed in RU486-treated glands. Using C4-HD tumors which only grow in the presence of MPA, we showed that FGF2 administered intratumorally was able to stimulate tumor growth as MPA. The histology of FGF2-treated tumors showed different degrees of gland differentiation. RU486 inhibited both, MPA or FGF2 induced tumor growth. However, only complete regression was observed in MPA-treated tumors. Our results support the hypothesis that stromal FGF2 activates PR inducing hormone independent tumor growth.

  4. Linear Accelerator (LINAC)

    ... News Physician Resources Professions Site Index A-Z Linear Accelerator A linear accelerator (LINAC) customizes high energy x-rays to ... ensured? What is this equipment used for? A linear accelerator (LINAC) is the device most commonly used ...

  5. Tsc1 deficiency impairs mammary development in mice by suppression of AKT, nuclear ERα, and cell-cycle-driving proteins.

    Qin, Zhenqi; Zheng, Hang; Zhou, Ling; Ou, Yanhua; Huang, Bin; Yan, Bo; Qin, Zhenshu; Yang, Cuilan; Su, Yongchun; Bai, Xiaochun; Guo, Jiasong; Lin, Jun

    2016-01-01

    Loss of Tsc1/Tsc2 results in excess cell growth that eventually forms hamartoma in multiple organs. Our study using a mouse model with Tsc1 conditionally knockout in mammary epithelium showed that Tsc1 deficiency impaired mammary development. Phosphorylated S6 was up-regulated in Tsc1(-/-) mammary epithelium, which could be reversed by rapamycin, suggesting that mTORC1 was hyperactivated in Tsc1(-/-) mammary epithelium. The mTORC1 inhibitor rapamycin restored the development of Tsc1(-/-) mammary glands whereas suppressed the development of Tsc1(wt/wt) mammary glands, indicating that a modest activation of mTORC1 is critical for mammary development. Phosphorylated PDK1 and AKT, nuclear ERα, nuclear IRS-1, SGK3, and cell cycle regulators such as Cyclin D1, Cyclin E, CDK2, CDK4 and their target pRB were all apparently down-regulated in Tsc1(-/-) mammary glands, which could be reversed by rapamycin, suggesting that suppression of AKT by hyperactivation of mTORC1, inhibition on nuclear ERα signaling, and down-regulation of cell-cycle-driving proteins play important roles in the retarded mammary development induced by Tsc1 deletion. This study demonstrated for the first time the in vivo role of Tsc1 in pubertal mammary development of mice, and revealed that loss of Tsc1 does not necessarily lead to tissue hyperplasia. PMID:26795955

  6. Inducible transgenics. New lessons on events governing the induction and commitment in mammary tumorigenesis

    Breast cancer arises from multiple genetic events that together contribute to the established, irreversible malignant phenotype. The development of inducible tissue-specific transgenics has allowed a careful dissection of the events required for induction and subsequent maintenance of tumorigenesis. Mammary gland targeted expression of oncogenic Ras or c-Myc is sufficient for the induction of mammary gland tumorigenesis in the rodent, and when overexpressed together the rate of tumor onset is substantially enhanced. In an exciting recent finding, D'Cruz et al discovered tetracycline-regulated c-Myc overexpression in the mammary gland induced invasive mammary tumors that regressed upon withdrawal of c-Myc expression. Almost one-half of the c-Myc-induced tumors harbored K-ras or N-ras gene point mutations, correlating with tumor persistence on withdrawal of c-Myc transgene expression. These findings suggest maintenance of tumorigenesis may involve a second mutation within the Ras pathway

  7. Cyclin D1 and mammary carcinoma: new insights from transgenic mouse models

    Cyclin D1 is one of the most commonly overexpressed oncogenes in breast cancer, with 45–50% of primary ductal carcinomas overexpressing this oncoprotein. Targeted deletion of the gene encoding cyclin D1 demonstrates an essential role in normal mammary gland development while transgenic studies provide evidence that cyclin D1 is a weak oncogene in mammary epithelium. In a recent exciting development, Yu et al. demonstrate that cyclin D1-deficient mice are resistant to mammary carcinomas induced by c-neu and v-Ha-ras, but not those induced by c-myc or Wnt-1. These findings define a pivotal role for cyclin D1 in a subset of mammary cancers in mice and imply a functional role for cyclin D1 overexpression in human breast cancer

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

    Rasmussen, Alice Neess; Nielsen, Mette Olaf; Tauson, Anne-Helene; Offenberg, Hanne Kjær; Thomsen, Preben Dybdahl; Blache, Dominique

    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...... interestingly, leptin increased markedly post-partum to reach a peak 2 days after parturition (P=0.01). Plasma leptin concentrations were higher pre-partum than post-partum (P<0.05), decreased at parturition and arterio-venous differences for leptin across the mammary gland were at no time significantly...... different from zero. Plasma leptin does thus not appear to be involved in regulation of milk leptin. Both leptin and the short cytoplasmic form of its receptor were expressed in the mammary gland. The highest leptin receptor expression was observed pre-partum and decreased post-partum. Expression of leptin...

  9. Tubulopapillary carcinoma of the mammary gland in a maned wolf (Chrysocyon brachyurus: histopathological and immunophenotypical analysis

    C.O. Gamba

    2011-12-01

    Full Text Available A maned female wolf (Chrysocyon brachyurus showed nodules in the inguinal and left abdominal cranial mammary glands. The mammary gland was surgically excised, and microscopic analysis revealed epithelial cell proliferation in a tubular and papillary pattern; delicate fibrovascular stalks presenting numerous layers of moderately pleomorfic epithelial cells were observed. This histologic appearance was compatible with a diagnosis of mammary tubulopapillary carcinoma. The immunohistochemical profile revealed nuclear positivity for estrogen (70% and progesterone (at least 90% of the neoplastic cells. The myoepithelium-associated with neoplastic cells lacked integrity, as evidenced by failed smooth muscle alpha actin reactivity in microinvasive areas. A low proliferation index was observed (3.4%. To the authors' knowledge, the present case represents the first finding of female tubulopapillary carcinoma in a mammary gland in this species.

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

    Mandrup, Karen Riiber; Johansson, Hanna Katarina Lilith; Boberg, Julie; Pedersen, Anne S.; Mortensen, Mette Sidsel; Jørgensen, Jennifer Solgaard; Vinggaard, Anne Marie; Hass, Ulla

    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...... of environmentally relevant EDCs with estrogenic, anti-androgenic or dissimilar modes of action (TotalMix) of 100-, 200- or 450-fold high end human intake estimates. Mammary glands of prepubertal and adult female and male offspring were examined. Oestrogens increased mammary outgrowth in prepubertal...... females and the mRNA level of matrix metalloproteinase-3, which may be a potential biomarker for increased outgrowth. Mixtures of EDCs gave rise to ductal hyperplasia in adult males. Adult female mammary glands of the TotalMix group showed morphological changes possibly reflecting increased prolactin...

  11. Salvage of a TRAM breast reconstruction flap using the retrograde internal mammary artery system

    Sameena Hassan

    2014-01-01

    Full Text Available Background: Free tissue transfer provides an optimal means for breast reconstruction in creating an aesthetically natural appearance that is durable over time. The choice of donor vessels vary from surgeon to surgeon, but the internal mammary axis is one of the most popular choices together with the thoracodorsal vessels. Aims and Results: We present the case of a salvaged free transverse rectus abdominis myocutaneous breast reconstruction in which end-to-end antegrade anastomosis to the internal mammary artery (IMA was not possible due to frail vessel walls, but retrograde anastomosis to the IMA and antegrade anastomosis of internal mammary vessel resulted in a perfused and viable flap. Conclusion: We suggest the use of the retrograde internal mammary arterial system for microsurgical anastomosis when the anterograde flow is not adequate, the vessel wall is friable, and when other more common options are not available.

  12. A Cytogenetic Footprint for Mammary Carcinomas Induced by PhIP in Rats

    Christian, A T

    2001-04-01

    PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine), a mutagen/carcinogen belonging to the class of heterocyclic amines (HCAs) found in cooked meats, is a mammary gland carcinogen in rats and has been implicated in the etiology of certain human cancers including breast cancer. To gain insight into the genomic alterations associated with PhIP-induced mammary gland carcinogenesis, we used comparative genomic hybridization (CGH) to examine chromosomal abnormalities in rat mammary carcinomas induced by PhIP, and for comparison, by DMBA (7,12-dimethylbenz[a]anthracene), a potent experimental mammary carcinogen. There was a consistent and characteristic pattern of chromosome-region loss in PhIP-induced carcinomas that clearly distinguished them from carcinomas induced by DMBA.

  13. Ischemia induced by coronary steal through a patent mammary artery side branch: a role for embolization.

    Moreno, Nuno; da Silva Castro, Alexandra; Pereira, Adriana; Silva, João Carlos; Almeida, Pedro Bernardo; Andrade, Aurora; Maciel, Maria Júlia; Pinto, Paula

    2013-06-01

    Non-occlusion of the internal mammary artery side branches may cause ischemia due to flow diversion after coronary artery bypass grafting. The authors present the case of a 67-year-old man with recurrent angina after undergoing myocardial revascularization with a left internal mammary artery to left anterior descending bypass. He presented with impaired anterior wall myocardial perfusion in the setting of a patent left internal mammary artery side branch. Effective percutaneous treatment was carried out through coil embolization, with improved flow and clinical symptoms, confirmed through ischemia testing. Coronary steal through a patent mammary artery side branch is a controversial phenomenon and this type of intervention should be considered only in carefully selected patients. PMID:23809629

  14. PIK3CA(H1047R)- and Her2-initiated mammary tumors escape PI3K dependency by compensatory activation of MEK-ERK signaling.

    Cheng, H; Liu, P; Ohlson, C; Xu, E; Symonds, L; Isabella, A; Muller, W J; Lin, N U; Krop, I E; Roberts, T M; Winer, E P; Arteaga, C L; Zhao, J J

    2016-06-01

    Human breast cancers that have HER2 amplification/overexpression frequently carry PIK3CA mutations, and are often associated with a worse prognosis. However, the role of PIK3CA mutations in the initiation and maintenance of these breast cancers remains elusive. In the present study, we generated a compound mouse model that genetically mimics HER2-positive breast cancer with coexisting PIK3CA(H1047R). Induction of PIK3CA(H1047R) expression in mouse mammary glands with constitutive expression of activated Her2/Neu resulted in accelerated mammary tumorigenesis with enhanced metastatic potential. Interestingly, inducible expression of mutant PIK3CA resulted in a robust activation of phosphatidylinositol-3-kinase (PI3K)/AKT signaling but attenuation of Her2/Her3 signaling, and this can be reversed by deinduction of PIK3CA(H1047R) expression. Strikingly, although these Her2(+) PIK3CA(H1047R)-initiated primary mammary tumors are refractory to HER2-targeted therapy, all tumors responded to inactivation of the oncogenic PIK3CA(H1047R), a situation closely mimicking the use of a highly effective inhibitor specifically targeting the mutant PIK3CA/p110a. Notably, these tumors eventually resumed growth, and a fraction of them escaped PI3K dependence by compensatory ERK activation, which can be blocked by combined inhibition of Her2 and MEK. Together, these results suggest that PIK3CA-specific inhibition as a monotherapy followed by combination therapy targeting MAPK and HER2 in a timely manner may be an effective treatment approach against HER2-positive cancers with coexisting PIK3CA-activating mutations. PMID:26640141

  15. Adjuvant therapy in case of mammary carcinoma (high risk)

    108 patients with high risk stage of a mammary carcinoma (four or more positive axillar lymph nodes) were submitted after surgery to a prospectively randomized study: a postirradiation in three series with additional administration of tamoxifen was opposed to a reduced-dose irradiation and subsequent simultaneous combination of polychemotherapy and irradiation. In patients with an age of less than 50 years, the combination of chemotherapy and radiotherapy caused a significant prolongation of the recurrence-free interval (>57 months versus 12,75 months). The comparison with literature shows that an average interval of 39.1 months without recurrences for the total group of patients treated with combination therapy corresponds to the result of a high-dose adjuvant CMF therapy. With respect to mean life expectancy, there was no significant difference between both groups of randomization. (orig.)

  16. Differential Glutamate Metabolism in Proliferating and Quiescent Mammary Epithelial Cells.

    Coloff, Jonathan L; Murphy, J Patrick; Braun, Craig R; Harris, Isaac S; Shelton, Laura M; Kami, Kenjiro; Gygi, Steven P; Selfors, Laura M; Brugge, Joan S

    2016-05-10

    Mammary epithelial cells transition between periods of proliferation and quiescence during development, menstrual cycles, and pregnancy, and as a result of oncogenic transformation. Utilizing an organotypic 3D tissue culture model coupled with quantitative metabolomics and proteomics, we identified significant differences in glutamate utilization between proliferating and quiescent cells. Relative to quiescent cells, proliferating cells catabolized more glutamate via transaminases to couple non-essential amino acid (NEAA) synthesis to α-ketoglutarate generation and tricarboxylic acid (TCA) cycle anaplerosis. As cells transitioned to quiescence, glutamine consumption and transaminase expression were reduced, while glutamate dehydrogenase (GLUD) was induced, leading to decreased NEAA synthesis. Highly proliferative human tumors display high transaminase and low GLUD expression, suggesting that proliferating cancer cells couple glutamine consumption to NEAA synthesis to promote biosynthesis. These findings describe a competitive and partially redundant relationship between transaminases and GLUD, and they reveal how coupling of glutamate-derived carbon and nitrogen metabolism can be regulated to support cell proliferation. PMID:27133130

  17. EGFR and microvessel density in canine malignant mammary tumours.

    Carvalho, Maria Isabel; Guimarães, Maria João; Pires, Isabel; Prada, Justina; Silva-Carvalho, Ricardo; Lopes, Carlos; Queiroga, Felisbina L

    2013-12-01

    The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor which has been shown to have an important role in human breast cancer. Its role appears to be associated with increased angiogenesis and metastasis. In order to clarify its role in canine mammary tumours (CMT), 61 malignant neoplasms were studied by using immunohistochemistry, comparing expression of EGFR, microvessel density (MVD) by CD31 immunolabelling and characteristics of tumour aggressiveness. High EGFR immunoexpression was statistically significantly associated with tumour size, tumour necrosis, mitotic grade, histological grade of malignancy and clinical stage. High CD31 immunoreactivity was statistically significantly associated with tubule formation, histological grade of malignancy and clinical stage. A positive correlation between EGFR and CD31 immunoexpression (r = 0.843; P aggression in malignant CMT, presenting the possibility of using EGFR inhibitors in the context of metastatic disease treatment. PMID:24091029

  18. Optical diagnosis of mammary ductal carcinoma using advanced optical technology

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, Shuangmu; Wang, Chuan; Chen, Jianxin

    2015-02-01

    Clinical imaging techniques for diagnosing breast cancer mainly include X-ray mammography, ultrasound, and magnetic resonance imaging (MRI), which have respective drawbacks. Multiphoton microscopy (MPM) has become a potentially attractive optical technique to bridge the current gap in clinical utility. In this paper, MPM was used to image normal and ductal cancerous breast tissues, based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Our results showed that MPM has the ability to exhibit the microstructure of normal breast tissue, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) lesions at the molecular level comparable to histopathology. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time histological diagnosis of mammary ductal carcinoma in vivo.

  19. Matrix metalloproteinases and their expression in mammary gland

    URIAJOSEA; ZENAWERB

    1998-01-01

    The matrix metalloproteinases (MMPs) are a family of zine-dependent endopeptidases that play a key role in both normal and pathological processes involving tissue remodeling events.The expression of these proteolytic enzymes is highly regulated by a balance between extracellular matrix (ECM) deposition and its degradation,and is controlled by growth factors,cytokines,hormones,as well as interactions with the ECM macromolecules.Furthermore,the activity of the MMPs is regulated by their natural endogenous inhibitors,which are members of the tissue inhibitor of metalloproteinases (TIMP) family.In the normal mammary gland,MMPs are expressed during ductal development,lobulo-alveolar development in pregnancy and involution after lactation.Under pathological conditions,such as tumorigenesis,the dysregulated expression of MMPs play a role in tumor initiation,progression and malignant conversion as well as facilitating invasion and metastasis of malignant cells through degradation of the ECM and basement membranes.

  20. Pea3 transcription factors and wnt1-induced mouse mammary neoplasia.

    Rebecca Baker

    Full Text Available The role of the PEA3 subfamily of Ets transcription factors in breast neoplasia is controversial. Although overexpression of PEA3 (E1AF/ETV4, and of the related factors ERM (ETV5 and ER81 (ETV1, have been observed in human and mouse breast tumors, PEA3 factors have also been ascribed a tumor suppressor function. Here, we utilized the MMTV/Wnt1 mouse strain to further interrogate the role of PEA3 transcription factors in mammary tumorigenesis based on our previous observation that Pea3 is highly expressed in MMTV/Wnt1 mammary tumors. Pea3 expression in mouse mammary tissues was visualized using a Pea3(NLSlacZ reporter strain. In normal mammary glands, Pea3 expression is predominantly confined to myoepithelial cells. Wnt1 transgene expression induced marked amplification of this cell compartment in nontumorous mammary glands, accompanied by an apparent increase in Pea3 expression. The pattern of Pea3 expression in MMTV/Wnt1 mammary glands recapitulated the cellular profile of activated beta-catenin/TCF signaling, which was visualized using both beta-catenin immunohistochemistry and the beta-catenin/TCF-responsive reporter Axin2(NLSlacZ. To test the requirement for PEA3 factors in Wnt1-induced tumorigenesis, we employed a mammary-targeted dominant negative PEA3 transgene, DeltaNPEA3En. Expression of DeltaNPEA3En delayed early-onset tumor formation in MMTV/Wnt1 virgin females (P = 0.03, suggesting a requirement for PEA3 factor function for Wnt1-driven tumor formation. Consistent with this observation, expression of the DeltaNPEA3En transgene was profoundly reduced in mammary tumors compared to nontumorous mammary glands from bigenic MMTV/Wnt1, MMTV/DeltaNPEA3En mice (P = 0.01. Our data provide the first description of Wnt1-mediated expansion of the Pea3-expressing myoepithelial compartment in nontumorous mammary glands. Consistent with this observation, mammary myoepithelium was selectively responsive to Wnt1. Together these data suggest the MMTV

  1. Pericentriolar Targeting of the Mouse Mammary Tumor Virus GAG Protein.

    Guangzhi Zhang

    Full Text Available The Gag protein of the mouse mammary tumor virus (MMTV is the chief determinant of subcellular targeting. Electron microscopy studies show that MMTV Gag forms capsids within the cytoplasm and assembles as immature particles with MMTV RNA and the Y box binding protein-1, required for centrosome maturation. Other betaretroviruses, such as Mason-Pfizer monkey retrovirus (M-PMV, assemble adjacent to the pericentriolar region because of a cytoplasmic targeting and retention signal in the Matrix protein. Previous studies suggest that the MMTV Matrix protein may also harbor a similar cytoplasmic targeting and retention signal. Herein, we show that a substantial fraction of MMTV Gag localizes to the pericentriolar region. This was observed in HEK293T, HeLa human cell lines and the mouse derived NMuMG mammary gland cells. Moreover, MMTV capsids were observed adjacent to centrioles when expressed from plasmids encoding either MMTV Gag alone, Gag-Pro-Pol or full-length virus. We found that the cytoplasmic targeting and retention signal in the MMTV Matrix protein was sufficient for pericentriolar targeting, whereas mutation of the glutamine to alanine at position 56 (D56/A resulted in plasma membrane localization, similar to previous observations from mutational studies of M-PMV Gag. Furthermore, transmission electron microscopy studies showed that MMTV capsids accumulate around centrioles suggesting that, similar to M-PMV, the pericentriolar region may be a site for MMTV assembly. Together, the data imply that MMTV Gag targets the pericentriolar region as a result of the MMTV cytoplasmic targeting and retention signal, possibly aided by the Y box protein-1 required for the assembly of centrosomal microtubules.

  2. Metabolomic Changes Accompanying Transformation and Acquisition of Metastatic Potential in a Syngeneic Mouse Mammary Tumor Model*

    Lu, Xin; Bennet, Bryson; Mu, Euphemia; Rabinowitz, Joshua; Kang, Yibin

    2010-01-01

    Breast cancer is the most common cancer type for women in the western world. Despite decades of research, the molecular processes associated with breast cancer progression are still inadequately defined. Here, we focus on the systematic alteration of metabolism by using the state of the art metabolomic profiling techniques to investigate the changes of 157 metabolites during the progression of normal mouse mammary epithelial cells to an isogenic series of mammary tumor cell lines with increas...

  3. Melatonin attenuates lipid peroxidation and enhances circulatory antioxidants during mammary carcinogenesis in rats

    Sankaran Mirunalini; Kandhan Karthishwaran; Ganesan Dhamodharan; Shalini Mohan

    2010-01-01

    The possible protective effect of Melatonin was investigated for its antioxidant and lipid peroxidation activity against 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis in female albino Wistar rats. Mammary tumor was developed to the animals by administering 5mg/kg body weight of DMBA orally at weekly intervals for one month. Intraperitoneal administration of melatonin 5mg/ml per animals for 15 days prior to the first oral administration of DMBA was continued for a month....

  4. Precocious mammary development in an 8-month-old Holstein heifer.

    Ambrose, Divakar J; Emmanuel, Daya G V

    2008-08-01

    An 8-month-old, virgin Holstein heifer with precocious mammary development was presented for examination. Protein, fat, and lactose in the mammary secretion were 14.90%, 0.12%, and 0.20%, respectively; somatic cell count was 3.9 x 10(6)/mL, with no bacterial infection. The heifer was inseminated at 15 months of age, confirmed pregnant, and subsequently slaughtered. PMID:18978977

  5. The significance of striated muscle in the mammary glands of marsupials.

    Griffiths, M; Slater, E

    1988-01-01

    The distribution and amounts of striated muscle within the mammary glands of pouched and pouchless marsupials from Australia and South America are described. Invasions into the mammary secretory parenchyma in pouchless marsupials by swathes of striated muscle from the ilio-marsupialis muscle are massive, in some instances concentrated into discrete muscles, which are inserted on to the bases of the teats; the name retractor mammae is proposed for these muscles. In pouched marsupials striated ...

  6. Embryonic mammary signature subsets are activated in Brca1-/- and basal-like breast cancers

    Zvelebil, Marketa; Oliemuller, Erik; Gao, Qiong; Wansbury, Olivia; Mackay, Alan; Kendrick, Howard; Matthew J Smalley; Reis-Filho, Jorge S.; Howard, Beatrice A

    2013-01-01

    Introduction Cancer is often suggested to result from development gone awry. Links between normal embryonic development and cancer biology have been postulated, but no defined genetic basis has been established. We recently published the first transcriptomic analysis of embryonic mammary cell populations. Embryonic mammary epithelial cells are an immature progenitor cell population, lacking differentiation markers, which is reflected in their very distinct genetic profiles when compared with ...

  7. Histological and Morphometric Study of Regressive Changes in the Mammary Glands of Pigs during Regression

    Svätoslav Hluchý; Norbert Bolcsó; Róbert Toman

    2011-01-01

    The work deals with the histological and morphometric description of regressive changes in the mammary glands of swine after lactation. Samples of mammary glands of thoracic, abdominal and pubic udders were taken soon after they were killed. Samples were processed by histological and histochemical methods and evaluated by subjective and quantitative morphometrical methods. It was found that post-lactation increases the relative volume of connective stroma up to 75.10 ± 14.76 % of collagen in ...

  8. THE ASSESSMENT OF THE PREVALENCE OF ASSOCIATED BENIGN PATHOLOGY OF THYROID AND MAMMARY GLANDS

    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...

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

    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.......22) did not reach significance. There were no significant correlations between piglet start weight and any of these mammary gland compositional traits....

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

    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.

  11. The Homeodomain Protein CDP Regulates Mammary-Specific Gene Transcription and Tumorigenesis

    Zhu, Quan; Maitra, Urmila; Johnston, Dennis; Lozano, Mary; Dudley, Jaquelin P.

    2004-01-01

    The CCAAT-displacement protein (CDP) has been implicated in developmental and cell-type-specific regulation of many cellular and viral genes. We previously have shown that CDP represses mouse mammary tumor virus (MMTV) transcription in tissue culture cells. Since CDP-binding activity for the MMTV long terminal repeat declines during mammary development, we tested whether binding mutations could alter viral expression. Infection of mice with MMTV proviruses containing CDP binding site mutation...

  12. Methods for preparing fluorescent and neutral red-stained whole mounts of mouse mammary glands

    Landua, John D.; Visbal, Adriana P.; Lewis, Michael T

    2009-01-01

    Whole mount preparations of mouse mammary glands are useful for evaluating overall changes in growth and morphology, and are essential for detecting and evaluating focal or regionally-localized phenotypes that would be difficult to detect or analyze using other techniques. We present three newly-developed methods for preparing whole mounts of mammary glands from genetically-engineered mice expressing fluorescent proteins, as well as using either neutral red or a variety of fluorescent dyes. U...

  13. Glucocorticoid regulation of mouse mammary tumor virus sequences in transgenic mice.

    Ross, S R; Solter, D

    1985-01-01

    We have introduced a chimeric plasmid, pLTR2TK, containing the mouse mammary tumor virus (MTV) long terminal repeat (LTR) linked to the herpes simplex virus type 1 thymidine kinase gene into the mouse germ line by microinjection. In one mouse line, the thymidine kinase gene is appropriately expressed in the lactating mammary glands of heterozygous females; expression also occurs in the ovaries of these mice. In heterozygous males of this line, and in a male derived from another microinjection...

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

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

    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 bee...

  15. Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein

    Wang, Jun; Jenkins, Sarah; Lamartiniere, Coral A.

    2014-01-01

    Background Humans are exposed to an array of both harmful and beneficial hormonally active compounds in the environment and through diet. Two such chemicals are Bisphenol A (BPA), a plasticizer, and genistein, a component of soy. Prepubertal exposure to BPA increased mammary carcinogenesis, while genistein suppressed cancer in a chemically-induced model of rodent mammary cancer. The purpose of this research was to determine the effects of combinational exposure to genistein and BPA on cell pr...

  16. Differential requirement of GRP94 and GRP78 in mammary gland development

    Genyuan Zhu; Miao Wang; Benjamin Spike; Gray, Peter C.; Jieli Shen; Sung-Hyung Lee; Si-Yi Chen; Lee, Amy S.

    2014-01-01

    Glucose Regulated Protein (GRP) 94 and GRP78 are critical molecular chaperones and regulators of signaling. Conditional knockout mouse models have revealed tissue specific requirements for GRP94 and GRP78, including selection for allele retention in specific cell types. Here we report the consequences of mammary-targeted knockout of these GRPs. Our studies revealed that MMTV-Cre, Grp94f/f mammary glands, despite GRP94 deficiency, exhibited normal proliferation and ductal morphogenesis. Intere...

  17. Cdc42 overexpression induces hyperbranching in the developing mammary gland by enhancing cell migration

    Bray, Kristi; Gillette, Melissa; Young, Jeanette; Loughran, Elizabeth; Hwang, Melissa; Sears, James Cooper; Vargo-Gogola, Tracy

    2013-01-01

    Introduction The Rho GTPase Cdc42 is overexpressed and hyperactivated in breast tumors compared to normal breast tissue. Cdc42 regulates key processes that are critical for mammary gland morphogenesis and become disrupted during the development, progression, and metastasis of breast cancer. However, the contribution of Cdc42 to normal and neoplastic mammary gland development in vivo remains poorly understood. We were therefore interested in investigating the effects of Cdc42 overexpression on...

  18. Inducible transgenics. New lessons on events governing the induction and commitment in mammary tumorigenesis

    Hulit, James; Di Vizio, Dolores; Pestell, Richard G.

    2001-01-01

    Breast cancer arises from multiple genetic events that together contribute to the established, irreversible malignant phenotype. The development of inducible tissue-specific transgenics has allowed a careful dissection of the events required for induction and subsequent maintenance of tumorigenesis. Mammary gland targeted expression of oncogenic Ras or c-Myc is sufficient for the induction of mammary gland tumorigenesis in the rodent, and when overexpressed together the rate of tumor onset is...

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

    Jefferson Filgueira Alcindo; Gabriel Isola Braga; Luis Claudio Nogueira Mendes; Márcia Marinho; Francisco Leydson Formiga Feitosa

    2016-01-01

    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-...

  20. Loss of intercellular junctional communication correlates with metastatic potential in mammary adenocarcinoma cells.

    Nicolson, G. L.; Dulski, K M; Trosko, J E

    1988-01-01

    A series of rat 13762NF mammary adenocarcinoma cell sublines and clones of various spontaneous pulmonary metastatic potentials from the mammary fat pads of syngeneic rats were examined for their intercellular junctional communication. Using the scrape-loading dye-transfer technique to introduce Lucifer yellow (Mr 457) into cells, we measured the abilities of 13762NF cells to transfer dye to adjacent cells. There was an excellent correlation between loss of Lucifer yellow dye transfer and spon...

  1. Histological and Morphometric Comparison of Lactating Mammary Glands in Pigs Depending on Their Location

    Svätoslav Hluchý; Róbert Toman; Mária Adamkovičová; Michal Cabaj

    2012-01-01

    In this paper we described a morphometric comparison of lactating mammary glands of pigs, depending on their location. As experimental animals were used five pig breeds White Meat at the age of 24 months. Anatomical dissection and sampling of the mammary glands of thoracic, abdomen and pubic udders for histological processing and subsequent quantitative morphometric evaluation were taken after killing the animals. It was found that glandular parenchyma, stroma connective tissue and adipose ti...

  2. Paclitaxel resistance in untransformed human mammary epithelial cells is associated with an aneuploidy-prone phenotype

    Bouchet, B P; Bertholon, J; Falette, N; Audoynaud, C; Lamblot, C; Puisieux, A; Galmarini, C M

    2007-01-01

    Despite its increasing clinical use, almost no data are currently available about paclitaxel effects on non-cancerous mammary epithelial cells. We have previously established paclitaxel-resistant sub-cell lines (paclitaxel-surviving populations, PSPs; n=20), and sensitive controls (control clones, CCs; n=10), from the untransformed human mammary epithelial cell line HME1. In this study, we aimed to establish whether paclitaxel resistance was associated with a modified sensitivity to paclitaxe...

  3. Proteins are secreted by both constitutive and regulated secretory pathways in lactating mouse mammary epithelial cells

    1992-01-01

    Lactating mammary epithelial cells secrete high levels of caseins and other milk proteins. The extent to which protein secretion from these cells occurs in a regulated fashion was examined in experiments on secretory acini isolated from the mammary glands of lactating mice at 10 d postpartum. Protein synthesis and secretion were assayed by following the incorporation or release, respectively, of [35S]methionine-labeled TCA-precipitable protein. The isolated cells incorporated [35S]methionine ...

  4. Presence of lung metastases in bitches affected by malignant mammary neoplasms in Medellin (Colombia)

    Brigitte Gómez J.; María Ramírez R.; Juan Maldonado E.

    2012-01-01

    ABSTRACTObjectives. To define the presence of lung metastasis in bitches with malignant mammary neoplasms. Material and methods. Thirty female dogs that were attended at Veterinary Hospital (University of Antioquia, Medellin, Colombia) were selected for the study. At consultation clinical variables and grade of mammary and inguinal lymph node compromise were registered. Latero-lateral and ventral-dorsal radiographic images of thorax were done for identification of radiographic lesions suggest...

  5. Development and Characterization of a Novel Rat Model of Estrogen-Induced Mammary Cancer

    Dennison, Kirsten L.; Samanas, Nyssa Becker; Harenda, Quincy Eckert; Hickman, Maureen Peters; Seiler, Nicole L.; Ding, Lina; Shull, James D.

    2015-01-01

    The ACI rat model of 17β-estradiol (E2)-induced mammary cancer is highly relevant for use in establishing the endocrine, genetic and environmental bases of breast cancer etiology and identifying novel agents and strategies for preventing breast cancer. E2 treatment rapidly induces mammary cancer in female ACI rats and simultaneously induces pituitary lactotroph hyperplasia and adenoma. The pituitary tumors can result in undesired morbidity which compromises long term studies focused on mammar...

  6. Mammary glands and feathers: Comparing two skin appendages which help define novel classes during vertebrate evolution

    Widelitz, Randall B; Veltmaat, Jacqueline M.; Mayer, Julie Ann; Foley, John; Chuong, Cheng-Ming

    2007-01-01

    It may appear counter-intuitive to compare feathers and mammary glands. However, through this Evo–Devo analysis, we appreciate how species interact with the environment, requiring different ectodermal organs. Novel ectodermal organs help define evolutionary directions, leading to new organism classes as exemplified by feathers for Aves and mammary glands for Mammals. Here, we review their structure, function, morphogenesis and regenerative cycling. Interestingly, both organs undergo extensive...

  7. GATA-3 Maintains the Differentiation of the Luminal Cell Fate in the Mammary Gland

    Kouros-Mehr, Hosein; Slorach, Euan M.; Sternlicht, Mark D.; Werb, Zena

    2006-01-01

    The GATA family of transcription factors plays fundamental roles in cell-fate specification. However, it is unclear if these genes are necessary for the maintenance of cellular differentiation after development. We identified GATA-3 as the most highly enriched transcription factor in the mammary epithelium of pubertal mice. GATA-3 was found in the luminal cells of mammary ducts and the body cells of terminal end buds (TEBs). Upon conditional deletion of GATA-3, mice exhibited severe defects i...

  8. The role of TG2 in regulating S100A4-mediated mammary tumour cell migration.

    Zhuo Wang

    Full Text Available The importance of S100A4, a Ca(2+-binding protein, in mediating tumour cell migration, both intracellularly and extracellularly, is well documented. Tissue transglutaminase (TG2 a Ca(2+-dependent protein crosslinking enzyme, has also been shown to enhance cell migration. Here by using the well characterised non-metastatic rat mammary R37 cells (transfected with empty vector and highly metastatic KP1 cells (R37 cells transfected with S100A4, we demonstrate that inhibition of TG2 either by TG2 inhibitors or transfection of cells with TG2 shRNA block S100A4-accelerated cell migration in the KP1cells and in R37 cells treated with exogenous S100A4. Cell migration was also blocked by the treatment with the non-cell permeabilizing TG2 inhibitor R294, in the human breast cancer cell line MDA-MB-231 (Clone 16, which has a high level of TG2 expression. Inhibition was paralleled by a decrease in S100A4 polymer formation. In vitro co-immunoprecipitation and Far Western blotting assays and cross-linking assays showed not only the direct interaction between TG2 and S100A4, but also confirmed S100A4 as a substrate for TG2. Using specific functional blocking antibodies, a targeting peptide and a recombinant protein as a competitive treatment, we revealed the involvement of syndecan-4 and α5β1 integrin co-signalling pathways linked by activation of PKCα in this TG2 and S100A4-mediated cell migration. We propose a mechanism for TG2-regulated S100A4-related mediated cell migration, which is dependent on TG2 crosslinking.

  9. IGF-1R inhibition in mammary epithelia promotes canonical Wnt signaling and Wnt1-driven tumors

    Rota, Lauren M.; Albanito, Lidia; Shin, Marcus E.; Goyeneche, Corey L.; Shushanov, Sain; Gallagher, Emily J.; LeRoith, Derek; Lazzarino, Deborah A.; Wood, Teresa L.

    2014-01-01

    Triple-negative breast cancers (TNBC) are an aggressive disease subtype which unlike other subtypes lack an effective targeted therapy. Inhibitors of the insullin-like growth factor receptor (IGF-1R) have been considered for use in treating TNBC. Here we provide genetic evidence that IGF-1R inhibition promotes development of Wnt1-mediated murine mammary tumors that offer a model of TNBC. We found that in a double transgenic mouse model carrying activated Wnt-1 and mutant IGF-1R, a reduction in IGF-1R signaling reduced tumor latency and promoted more aggressive phenotypes. These tumors displayed a squamal cell phenotype with increased expression of keratins 5/6 and β-catenin. Notably, cell lineage analyses revealed an increase in basal (CD29hi/CD24+) and luminal (CD24+/CD61+/CD29lo) progenitor cell populations, along with increased Nanog expression and decreased Elf5 expression. In these doubly transgenic mice, lung metastases developed with characteristics of the primary tumors, unlike MMTV-Wnt1 mice. Mechanistic investigations showed that pharmacological inhibition of the IGF-1R in vitro was sufficient to increase the tumorsphere-forming efficiency of MMTV-Wnt1 tumor cells. Tumors from doubly transgenic mice also exhibited an increase in the expression ratio of the IGF-II-sensitive, A isoform of the insulin receptor vs the IR-B isoform, which in vitro resulted in enhanced expression of β-catenin. Overall, our results revealed that in Wnt-driven tumors an attenuation of IGF-1R signaling accelerates tumorigenesis and promotes more aggressive phenotypes, with potential implications for understanding TNBC pathobiology and treatment. PMID:25092896

  10. Asymmetry of mammary glands in adult women with asymmetric pectus excavatum

    The purpose of this study was to examine the asymmetry of mammary glands in adult women with asymmetric pectus excavatum (PE). We measured the areas of bilateral mammary glands from CT images, and integrated those in all slices to calculate the volume of the mammary glands. The volume ratio of bilateral mammary glands between PE patients (n=23) and the normal control group (n=14) was measured. To examine asymmetry of the chest depression, the sternal rotation angle was measured and a rotation angle of more than 30 degrees was diagnosed as severe asymmetric deformity (n=12). The mean volume ratio of mammary glands in PE (0.9±0.19) was not significantly different from normal control (1.02±0.15). However, in severe asymmetric PE patients, the ratio (0.86±0.13) was significantly smaller than normal. In adult women with asymmetric PE, the volume of mammary glands is also asymmetric. In PE patients with severe asymmetric breast proportion, the Nuss procedure plus breast augmentation is recommended. (author)

  11. Epithelial cell differentiation regulated by MicroRNA-200a in mammary glands.

    Kentaro Nagaoka

    Full Text Available Mammary gland epithelial cells undergo periodic cycles of proliferation, differentiation, and involution. Many studies have reported that miRNAs, which are small, non-coding RNAs, influence a variety of biological processes during posttranscriptional regulation. Here, we found that one miRNA, miR-200a, was relatively highly expressed in epithelial cell-rich organs such as mammary glands, lung, and kidney in mice. In mammary glands, miR-200a expression increased during mid-pregnancy through lactation; its expression was stimulated by lactogenic hormone treatment of mammary epithelial cells. Lactogenic hormone also induced the expression of milk protein ß-casein mRNA (a marker of cell differentiation and E-cadherin mRNA (a marker of epithelial cells. However, knockdown of miR-200a prevented increases in ß-casein and E-cadherin mRNA expression. Protein analysis revealed that E-cadherin signal was decreased and ZEB1 (a marker of EMT was increased following miR-200a knockdown. Finally, in a three-dimensional culture system modeling lumen-containing mammary ducts, miR-200a knockdown decreased the cavity formation rate and suppressed claudin-3 and par-6b expression, indicating reduced epithelial cell polarity. These observations suggest that miR-200a is important for maintaining the epithelial cell phenotype, which contributes to lactogenic hormone induction of cellular differentiation in mammary glands.

  12. Biological and genetic properties of the p53 null preneoplastic mammary epithelium

    Medina, Daniel; Kittrell, Frances S.; Shepard, Anne; Stephens, L. Clifton; Jiang, Cheng; Lu, Junxuan; Allred, D. Craig; McCarthy, Maureen; Ullrich, Robert L.

    2002-01-01

    The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.

  13. Arterial anatomosurgical segments of the mammary glands in dogs (Canis familiaris, Linnaeus, 1758)

    Thirty mammary complexes (sixty antimers) from cross bred multiparous bitches, were injected with latex and then studied by means of radiology and dissection. The different anatomo-surgical arterial segments thus obtained were identified and designated according to the anatomical zone of irrigation of each mammary gland as follows: 1. Thoracic segment, by means of the fourth and fifth perforant arteries, penetrates the first mammary gland in 85% of the cases; 2. Thoracoabdominal segment, by means of the sixth and seventh perforant arteries, penetrates the second mammary gland in 48.33 % of the cases. This segment can also be divided as follows: 2.1. Retrograde branches of the cranial superficial epigastric artery that penetrates the second mammary gland in about 51.66% of the cases, as the toracoabdominal cranial segment; 2.2. Terminal branches of the last artery penetrate the third mammary gland in 73.32% of the cases, as the toracoabdominal caudal segment. 3. Inguinoabdominal segment may also possess two sub-- segments: 3.1. Caudal superficial epigastric artery with primary branches penetrating the fourth mamma and the ventral labial branches, penetrating the fifth mamma in 96.66% of the cases, as inguinoabdomninal caudal segment. 3.2. Terminal branches of the caudal superficial epigastric artery penetrates the third mamma in 51.66% of the cases as inguinoabdominal cranial segment. The anastomosis observed in 78.33% of the cases may not have significance in mastectomy

  14. Immunodetection of myeloid and plasmacytoid dendritic cells in mammary carcinomas of female dogs

    Mayara C. Rosolem

    2015-11-01

    Full Text Available ABSTRACT: Dendritic cells have attracted great interest from researchers as they may be used as targets of tumor immune evasion mechanisms. The main objective of this study was to evaluate the relationship between the dendritic cells (DCs subpopulation in simple type mammary carcinomas in female dogs. Two groups of samples were used: the control group consisted of 18 samples of mammary tissue without changes and the tumor group with 26 simple type mammary carcinomas. In these groups, we evaluated the immunodetection of immature and mature myeloid DCs, plasmacytoid DCs and MHC-II. In mammary tumor, mature myeloid DCs predominated in the peritumoral region, while immature myeloid DCs and plasmacytoid DCs were evident in the intratumoral region. Immunostaining of MHC-II was visualized in mammary acini (control group, in tumor cells and inflammatory infiltration associated with tumors. The comparison between the control and tumor groups showed a statistically significant difference between immature myeloid DCs, mature myeloid DCs and plasmacytoid DCs. The immunodetection of MHC-II was not significant when comparing the groups. The predominance of immature DCs in the tumor group is possibly related to an inefficient immune response, promoting the development and survival of tumor cells. The presence of plasmacytoid DCs in the same group suggests a worse prognosis for female dogs with mammary tumors. Therefore, the ability of differentiation of canine dendritic cells could be influenced by neoplastic cells and by the tumor microenvironment.

  15. Positive correlation of steroid hormones and EGF in canine mammary cancer.

    Queiroga, Felisbina L; Pérez-Alenza, Dolores; Silvan, Gema; Peña, Laura; Illera, Juan C

    2009-05-01

    There are no published studies focused on the potential crosstalk between steroid hormones and EGF in canine mammary tumourigenesis. The objective was to investigate the role of EGF in canine mammary tumours (CMT) and the relationship with steroid hormones. Sixty-three CMT (39 malignant including 10 inflammatory mammary carcinomas (IMC); 19 benign and 5 dysplasias), and 13 normal mammary glands from dogs without history of neoplastic disease were analysed. Levels of EGF and steroid hormones [progesterone (P4); 17beta-estradiol (E2); androstenedione (A4) and dehydroepiandrosterone (DHEA)], were analysed by EIA in CMT homogenates. Levels of EGF were significantly higher in malignant compared with benign tumours, dysplasias and normal mammary glands (pIMC presented the highest EGF levels, with statistical significant difference between IMC and non-IMC cases (pIMC and IMC), a strong correlation was observed between EGF and: P4 (r=0.452; p=0.003); E2 (r=0.624; p=0.023); A4 (r=0.496; p=0.038); DHEA (r=0.431; p=0.005). These results suggest that EGF is implicated in canine mammary tumourigenesis. The positive correlation observed, opens an interesting perspective of interaction that should be further investigated. PMID:19429455

  16. Trefoil Factor 3 Is Oncogenic and Mediates Anti-Estrogen Resistance in Human Mammary Carcinoma

    Nagarajan Kannan

    2010-12-01

    Full Text Available We report herein that trefoil factor 3 (TFF3 is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. Forced expression of TFF3 in mammary carcinoma cells increased cell proliferation and survival, enhanced anchorage-independent growth, and promoted migration and invasion. Moreover, forced expression of TFF3 increased tumor size in xenograft models. Conversely, depletion of endogenous TFF3 with small interfering RNA (siRNA decreased the oncogenicity and invasiveness of mammary carcinoma cells. Neutralization of secreted TFF3 by antibody promoted apoptosis, decreased cell growth in vitro, and arrested mammary carcinoma xenograft growth. TFF3 expression was significantly correlated to decreased survival of estrogen receptor (ER-positive breast cancer patients treated with tamoxifen. Forced expression of TFF3 in mammary carcinoma cells increased ER transcriptional activity, promoted estrogen-independent growth, and produced resistance to tamoxifen and fulvestrant in vitro and to tamoxifen in xenograft models. siRNA-mediated depletion or antibody inhibition of TFF3 significantly enhanced the efficacy of antiestrogens. Increased TFF3 expression was observed in tamoxifen-resistant (TAMR cells and antibody inhibition of TFF3 in TAMR cells improved tamoxifen sensitivity. Functional antagonism of TFF3 therefore warrants consideration as a novel therapeutic strategy for mammary carcinoma.

  17. Presence of lung metastases in bitches affected by malignant mammary neoplasms in Medellin (Colombia

    Brigitte Gómez J.

    2012-08-01

    Full Text Available Objective. To define the presence of lung metastasis in bitches with malignant mammary neoplasms. Materials and methods. Thirty female dogs that were attended at Veterinary Hospital (University of Antioquia, Medellin, Colombia were selected for the study. At consultation clinical variables and grade of mammary and inguinal lymph node compromise were registered. Latero-lateral and ventral-dorsal radiographic images of thorax were done for identification of radiographic lesions suggestive of lung metastasis. At surgery biopsies of affected mammary glands were taken for histopathological study and classification of tumors. Data were analyzed by descriptive statistics. Results. The average (± standard error age at clinical diagnosis was 10.87±2.65 year old. French poodle (46.6% cross-breed (13.3% and Schnauzer (10% were the breeds most frequently affected by mammary tumors. The most frequent tumor found was carcinoma (81%, followed by adenoma (8.1%, and other types (10.8%. The most frequently affected mammary glands by tumors were the right and the left inguinal glands (70% and 66.6%, respectively. Five out of 30 bitches (16.6% had lung metastasis according to radiographic examination. From this group of dogs, 4 out of 5 neoplasms (80% were diagnosed as complex carcinoma by histopathology diagnosis. Conclusions. We provide evidence suggesting that complex carcinoma is the most frequent mammary tumor in bitches in our city and it is highly related to lung metastasis.

  18. Influence of catechol-O-methyltransferase (COMT) genotypes on the prognosis of canine mammary tumors.

    Dias Pereira, P; Lopes, C C; Matos, A J F; Pinto, D; Gärtner, F; Lopes, C; Medeiros, R

    2009-11-01

    Catechol-O-methyltransferase (COMT) is an important enzyme involved in inactivation of catechol estrogens, which are metabolites with carcinogenic properties. Some investigations in human breast cancer associate a genetic polymorphism in the COMT gene (COMT val158met) with an increased risk and poor clinical progression of the disease. In dogs, there are 2 recognized single nucleotide polymorphisms in the COMT gene (COMTG216A and COMTG482A); however, their influence on the outcome of mammary neoplasms has never been investigated. The purpose of this study is to investigate the influence of COMT in the clinical progression of canine mammary tumors, namely in recurrence, metastasis and survival by testing 2 SNPs (G216A and G482A), and 2 genotypes of the COMT gene. A case series was conducted analyzing genomic DNA samples by polymerase chain reaction-restriction fragment length polymorphism from 80 bitches with mammary tumors. Animals were submitted to an active follow-up study for a period of 24 months after surgery. We observed that bitches carrying both genetic variations simultaneously are more likely to develop recurrence of mammary lesions. Our results demonstrate a possible role for COMT genotypes in the outcome of mammary neoplasms in the dog. Identifying a genetic factor predictive of recurrence may be useful in selecting the most effective surgical approach for canine mammary neoplasms. PMID:19605895

  19. /sup 20/neon ion- and x-ray-induced mammary carcinogenesis in female rats

    Shellabarger, C.J.; Baum, J.W.; Holtzman, S.; Stone, J.P.

    1983-01-01

    One of the proposed uses of heavy ion irradiation is to image lesions of the human female breast. The rat model system was chosen to assess the carcinogenic potential of heavy ion irradiation in the belief that data obtained from rat studies would have a qualitatively predictive value for the human female. Accordingly, female rats were exposed to /sup 20/Ne ions at the BEVALAC and studied for the development of mammary neoplasia for 312 +- 2 days at Brookhaven along with rats exposed concurrently to x-irradiation or to no irradiation. As the dose of either type of radiation was increased the percent of rats with mammary adenocarcinomas, and the percent of rats with mammary fibroadenomas, tended to increase. At a prevalence of 20%, the RBE for /sup 20/Neon ions for mammary adenocarcinomas was estimated to be larger than 5 and for mammary fibroadenomas the RBE was estimated to be less than 2. No conclusion was reached concerning whether or not the RBE might vary with dose. We suggest that /sup 20/Ne ions do have a carcinogenic potential for rat mammary tissue and that this carcinogenic potential is likely to be greater than for x-irradiation. (DT)

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

    Hvid, Henning; Ekstrøm, Claus T; Vienberg, Sara Gry; Oleksiewicz, Martin B; Klopfleisch, Robert

    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 of...

  1. A comparative study of the biologic and molecular basis of murine mammary carcinoma: a model for human breast cancer

    Tritiated-DNA complementary to mouse mammary tumor virus (MMTV) RNA was synthesized in an endogeneous reaction with MMTV particles. This DNA was used as a probe via molecular hybridization to detect MMTV-specific RNA in 'spontaneous' mammary tumors of several strains of mice, including the 'nonproducer' BALB/c mammary tumors. MMTV-specific RNA was also found in certain normal tissues (spleen, kidney, and epididymis) of a high-mammary-cancer strain (GR). Aging or treatment with nonviral carcinogens also induced the appearance of MMTV-specific RNA in certain normal tissues of the low-mammary-cancer strains, C57BL and BALB/c. The relationship of the presence of MMTV-specific RNA to the etiology and pathogenesis of murine mammary neoplasia and its potential application to human breast cancer are discussed

  2. Acceleration without Horizons

    Doria, Alaric; Munoz, Gerardo

    2015-01-01

    We derive the metric of an accelerating observer moving with non-constant proper acceleration in flat spacetime. With the exception of a limiting case representing a Rindler observer, there are no horizons. In our solution, observers can accelerate to any desired terminal speed $v_{\\infty} < c$. The motion of the accelerating observer is completely determined by the distance of closest approach and terminal velocity or, equivalently, by an acceleration parameter and terminal velocity.

  3. Ha-ras oncogene activation in mammary glands of N-methyl-N-nitrosourea-treated rats genetically resistant to mammary adenocarcinogenesis.

    Lu, S J; Archer, M.C.

    1992-01-01

    A single dose of N-methyl-N-nitrosourea given to sexually immature female Buf/N rats produces a high incidence of mammary adenocarcinomas. A large percentage of these tumors contain the Ha-ras oncogene, activated by a G----A transition at the second nucleotide of codon 12. Copenhagen rats, on the other hand, are completely resistant to mammary tumor induction by a number of carcinogens, including N-methyl-N-nitrosourea. Here we show, using a sensitive method involving PCR, that codon 12 Ha-ra...

  4. Lipoestructura y relleno del polo superior de la mama frente a implantes Structural fat graft and lipofilling of mammary upper pole versus mammary implants

    J.M. Cervilla Lozano

    2012-09-01

    Full Text Available La lipoestructura mamaria ofrece nuevas alternativas de tratamiento en la cirugía estética de aumento mamario, cumpliendo en algunos casos las expectativas esperadas y en otros no. Analizamos este hecho en 4 tipos de aplicación de lipoestructura mamaria que hemos venido realizando en los últimos años, centrándonos en un aspecto importante de esta cirugía que es el relleno del polo superior de la mama. Los tipos de aplicación empleados son: aumento mamario simple mediante lipoestructura en comparación con implantes; pexia más lipoestructura frente a pexia más implantes mamarios; reconstrucción de mama tuberosa mediante lipoestructura o implantes y finalmente, relleno periprotésico mediante lipoestructura en mamas sometidas a cirugía de aumento mamario con implantes. En definitiva, podríamos resumir este trabajo en una frase diciendo que la lipoestructura mamaria, a nuestro juicio, no sirve si lo que prima es conseguir el relleno del polo superior de la mama, siendo en este caso de elección la colocación de implantes mamarios. No obstante, en alguno de los casos señalados no solo es una alternativa, sino que obtiene resultados superiores a los logrados sólamente con implantes.The mammary structural fat graft offers news treatment options in breast augmentation cosmetic surgery, but it sometimes meets expectations and sometimes doesn´t. We analyze 4 different types of lipostructure mammary applications that we have been using in the last years, focused in an important aspect of this surgery as it´s the filling of the upper mammary pole. These applications are: mammary augmentation by simple structural fat compared with the use of mammary implants; structural fat graft and mastopexy versus implants and mastopexy; tuberous breast reconstruction using structural fat graft or implants and finally, periprosthetic filling in breast augmentation with mammary implants using structural fat graft. In short, we could summarize this paper

  5. Streptococcus uberis strains isolated from the bovine mammary gland evade immune recognition by mammary epithelial cells, but not of macrophages.

    Günther, Juliane; Czabanska, Anna; Bauer, Isabel; Leigh, James A; Holst, Otto; Seyfert, Hans-Martin

    2016-01-01

    Streptococcus uberis is frequently isolated from the mammary gland of dairy cattle. Infection with some strains can induce mild subclinical inflammation whilst others induce severe inflammation and clinical mastitis. We compared here the inflammatory response of primary cultures of bovine mammary epithelial cells (pbMEC) towards S. uberis strains collected from clinical or subclinical cases (seven strains each) of mastitis with the strong response elicited by Escherichia coli. Neither heat inactivated nor live S. uberis induced the expression of 10 key immune genes (including TNF, IL1B, IL6). The widely used virulent strain 0140J and the avirulent strain, EF20 elicited similar responses; as did mutants defective in capsule (hasA) or biofilm formation (sub0538 and sub0539). Streptococcus uberis failed to activate NF-κB in pbMEC or TLR2 in HEK293 cells, indicating that S. uberis particles did not induce any TLR-signaling in MEC. However, preparations of lipoteichoic acid (LTA) from two strains strongly induced immune gene expression and activated NF-κB in pbMEC, without the involvement of TLR2. The immune-stimulatory LTA must be arranged in the intact S. uberis such that it is unrecognizable by the relevant pathogen receptors of the MEC. The absence of immune recognition is specific for MEC, since the same S. uberis preparations strongly induced immune gene expression and NF-κB activity in the murine macrophage model cell RAW264.7. Hence, the sluggish immune response of MEC and not of professional immune cells to this pathogen may aid establishment of the often encountered belated and subclinical phenotype of S. uberis mastitis. PMID:26738804

  6. Dome formation in cell cultures as expression of an early stage of lactogenic differentiation of the mammary gland

    I. Zucchi; L. Bini; Albani, D.; Valaperta, R.; Liberatori, S.; Raggiaschi, R.; C. Montagna; Susani, L.; Barbieri, O.; Pallini, V.; Vezzoni, P.; Dulbecco, R.

    2002-01-01

    The study of the development of the mammary gland at the molecular level in the animal is difficult because of the complex tissue organization of the gland. We have previously developed an in vitro system for genetic analysis of mammary cell differentiation, based on the cell line LA7 clonally derived from a rat mammary adenocarcinoma. This cell line, after induction with DMSO, differentiates forming structures called domes. This process is under strict gene regulation, and we have previously...

  7. Paracrine signaling through the epithelial estrogen receptor α is required for proliferation and morphogenesis in the mammary gland

    Mallepell, Sonia; Krust, Andrée; Chambon, Pierre; Brisken, Cathrin

    2006-01-01

    Estradiol is a major regulator of postnatal mammary gland development and thought to exert its effects through estrogen receptor α (ERα) expressed in the mammary gland stroma and epithelium. Previous studies, however, were confounded by the use of an ERα mutant strain that retains some of the protein with transactivation activity. Here, we use an ERα−/− mouse strain in which no ERα transcript can be detected to analyze mammary gland development in the complete absence of ERα signaling. The ER...

  8. Expression of keratin 19, Na-K-Cl cotransporter and estrogen receptor alpha in developing mammary glands of ewes

    M. Colitti

    2011-01-01

    Mammary gland remodelling is strictly related to intracellular signals and stem cell biology. Among the best candidates to identify the nature and development of mammary cells are cytokeratin 19 (CK19), the Na-K-Cl cotransporter (NKCC1) and receptor of estrogen alpha (ERα). In this study, we analyzed the expression of these genes in ewe mammary glands from prepubertal stage to involution. Using Real time PCR we showed that NKCC1 transcription was significantly down regulated during lactation ...

  9. Epithelial cell-directed efferocytosis in the post-partum mammary gland is necessary for tissue homeostasis and future lactation

    Earp H Shelton

    2010-12-01

    Full Text Available Abstract Background Mammary glands harbor a profound burden of apoptotic cells (ACs during post-lactational involution, but little is known regarding mechanisms by which ACs are cleared from the mammary gland, or consequences if this process is interrupted. We investigated AC clearance, also termed efferocytosis, during post-lactational remodeling, using mice deficient for MerTK, Axl, and Tyro3, three related receptor tyrosine kinases (RTKs regulating macrophage-mediated efferocytosis in monocytes. MerTK expression, apoptosis and the accumulation of apoptotic debris were examined in histological sections of MerTK-deficient, Axl/Tyro3-deficient, and wild-type mammary glands harvested at specific time points during lactation and synchronized involution. The ability of primary mammary epithelial cells (MECs to engulf ACs was assessed in culture. Transplant of MerTK-deficient mammary epithelium into cleared WT mammary fat pads was used to assess the contribution of WT mammary macrophages to post-lactational efferocytosis. Results ACs induced MerTK expression in MECs, resulting in elevated MerTK levels at the earliest stages of involution. Loss of MerTK resulted in AC accumulation in post-lactational MerTK-deficient mammary glands, but not in Axl and Tyro3-deficient mammary glands. Increased vascularization, fibrosis, and epithelial hyperproliferation were observed in MerTK-deficient mammary glands through at least 60 days post-weaning, due to failed efferocytosis after lactation, but did not manifest in nulliparous mice. WT host-derived macrophages failed to rescue efferocytosis in transplanted MerTK-deficient mammary epithelium. Conclusion Efferocytosis by MECs through MerTK is crucial for mammary gland homeostasis and function during the post-lactational period. Efferocytosis by MECs thus limits pathologic consequences associated with the apoptotic load following lactation.

  10. Genetically determined inflammatory-response related cytokine and chemokine transcript profiles between mammary carcinoma resistant and susceptible rat strains

    Devapatla, Bharat; Sanders, Jennifer; Samuelson, David J.

    2012-01-01

    Multiple human breast and rat mammary carcinoma susceptibility (Mcs) alleles have been identified. Wistar Kyoto (WKY) rats are resistant to developing mammary carcinomas, while Wistar Furth (WF) females are susceptible. Gene transcripts at Mcs5a1, Mcs5a2, and Mcs5c are differentially expressed between resistant WKY and susceptible WF alleles in immune-system tissues. We hypothesized that immune-related gene transcript profiles are genetically determined in mammary carcinoma resistant and susc...

  11. Changes in gene expression during the development of mammary tumors in MMTV-Wnt-1 transgenic mice

    Huang, Shixia; Li, Yi; Chen, Yidong; Podsypanina, Katrina; Chamorro, Mario; Olshen, Adam B.; Desai, Kartiki V.; Tann, Anne; Petersen, David; Green, Jeffrey E; Varmus, Harold E.

    2005-01-01

    Background In human breast cancer normal mammary cells typically develop into hyperplasia, ductal carcinoma in situ, invasive cancer, and metastasis. The changes in gene expression associated with this stepwise progression are unclear. Mice transgenic for mouse mammary tumor virus (MMTV)-Wnt-1 exhibit discrete steps of mammary tumorigenesis, including hyperplasia, invasive ductal carcinoma, and distant metastasis. These mice might therefore be useful models for discovering changes in gene exp...

  12. Manganese superoxide dismutase is dispensable for post-natal development and lactation in the murine mammary gland

    Case, Adam J.; Frederick E. Domann

    2012-01-01

    Mammary gland development is a multistage process requiring tightly regulated spatial and temporal signalling pathways. Many of these pathways have been shown to be sensitive to oxidative stress. Understanding that the loss of manganese superoxide dismutase (Sod2) leads to increased cellular oxidative stress, and that the loss or silencing of this enzyme has been implicated in numerous pathologies including those of the mammary gland, we sought to examine the role of Sod2 in mammary gland dev...

  13. Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium

    Miyoshi, Keiko; Shillingford, Jonathan M.; Smith, Gilbert H.; Grimm, Sandra L.; Wagner, Kay-Uwe; Oka, Takami; Rosen, Jeffrey M.; Robinson, Gertraud W.; Hennighausen, Lothar

    2001-01-01

    Functional development of mammary epithelium during pregnancy depends on prolactin signaling. However, the underlying molecular and cellular events are not fully understood. We examined the specific contributions of the prolactin receptor (PrlR) and the signal transducers and activators of transcription 5a and 5b (referred to as Stat5) in the formation and differentiation of mammary alveolar epithelium. PrlR- and Stat5-null mammary epithelia were transplanted into wild-type hosts, and pregnan...

  14. Effects of Chinese herbal medicine for warming kidney on proliferation of normal human mammary epithelial cells in primary culture

    Ye, Mei-na; Chen, Hong-feng

    2006-01-01

    Objective: To evaluate the effects of Chinese herbal medicine for warming kidney on proliferation of normal human mammary epithelial cells in primary culture. Methods: The normal human mammary epithelial cells were dissociated by digestion with collagenase type Ⅰ. The morphological identification of normal human mammary epithelial cells in primary culture was determined under inverted phase contrast microscope and transmission electron microscope. The estradiol and progesterone were added to ...

  15. Time-lapse Imaging of Primary Preneoplastic Mammary Epithelial Cells Derived from Genetically Engineered Mouse Models of Breast Cancer

    Nakles, Rebecca E.; Millman, Sarah L.; Cabrera, M. Carla; Johnson, Peter; Mueller, Susette; Hoppe, Philipp S.; Schroeder, Timm; Furth, Priscilla A.

    2013-01-01

    Time-lapse imaging can be used to compare behavior of cultured primary preneoplastic mammary epithelial cells derived from different genetically engineered mouse models of breast cancer. For example, time between cell divisions (cell lifetimes), apoptotic cell numbers, evolution of morphological changes, and mechanism of colony formation can be quantified and compared in cells carrying specific genetic lesions. Primary mammary epithelial cell cultures are generated from mammary glands without...

  16. Loss of vitamin D receptor signaling from the mammary epithelium or adipose tissue alters pubertal glandular development

    Johnson, Abby L.; Zinser, Glendon M.; Waltz, Susan E.

    2014-01-01

    Vitamin D3 receptor (VDR) signaling within the mammary gland regulates various postnatal stages of glandular development, including puberty, pregnancy, involution, and tumorigenesis. Previous studies have shown that vitamin D3 treatment induces cell-autonomous growth inhibition and differentiation of mammary epithelial cells in culture. Furthermore, mammary adipose tissue serves as a depot for vitamin D3 storage, and both epithelial cells and adipocytes are capable of bioactivating vitamin D3...

  17. Radiotherapy of breast or left wall and of ganglionary areas including the internal mammary chain: dosimetric comparison of different ballistics

    As the irradiation of the mammary chain is still a matter of controversy because of non negligible toxicity risks, the authors report the comparison of three different irradiation ballistics for the breast or left wall as well as for ganglionary areas: short ballistics of internal mammary chains, long ballistics of internal mammary chains, and ballistics in tangential beams. Target volumes and organs at risk have been delineated, and dose-volume histograms have been compared. Short communication

  18. Expression of Putative Stem Cell Marker, Hepatocyte Nuclear Factor 4 Alpha, in Mammary Gland of Water Buffalo.

    Choudhary, Ratan K; Choudhary, Shanti; Kaur, Harmanjot; Pathak, Devendra

    2016-01-01

    Buffaloes account for more than 56% of total milk production in India. Cyclic remodeling of mammary glands of human, mice, cow, sheep, and goat is determined by mammary stem cells. It is logical to assume that buffalo mammary gland will have mammary stem/progenitor cells. Thus far, no report exists on identification of buffalo mammary stem cells. Hepatocyte nuclear factor 4 alpha (HNF4A) is a candidate marker for hepatic progenitor cells and has recently been suggested as a marker of bovine mammary stem/progenitor cells. We hypothesized that ( 1 ) HNF4A identifies putative buffalo mammary stem/progenitor cells and ( 2 ) the number of HNF4A-positive cells increases during mastitis. Sixteen buffalo mammary samples were collected from a local slaughterhouse. Hematoxylin and eosin staining were performed on 5-micron thick sections and on the basis of gross examination and histomorphology of the mammary glands, physiological stages of the animals were estimated as non-lactating (n = 4), mastitis (n = 9), and prepubertal (n = 3). In total, 24048 cells were counted (5-10 microscopic fields/animal; n = 16 animals) of which, 40% cells were mammary epithelial cells (MEC) and 60% cells were the stromal cells. The percentage of MEC in non-lactating animals was higher compared to mastitic animals (47.3% vs. 37.3%), which was likely due to loss of MEC in mastitis. HNF4A staining was observed in nuclei of MEC of ducts, alveoli, and stromal cells. Basal location and low frequency of HNF4A-positive MEC (ranges from 0.4-4.5%) were consistent with stem cell characteristics. Preliminary study showed coexpression of HNF4A with MSI1 (a mammary stem cell marker in sheep), suggesting HNF4A was likely to be a putative mammary stem/progenitor cell marker in buffalo. HNF4A-positive MEC (basal and luminal; light and dark stained) tended to be higher in non-lactating than the mastitic animals (8.73 ± 1.71% vs. 4.29 ± 1.19%; P = 0.07). The first hypothesis that HNF4A identify

  19. Charles River Sprague Dawley Rats Lack Early Age-Dependent Susceptibility to DMBA-Induced Mammary Carcinogenesis

    R.B. Gear, M. Yan, J. Schneider, P. Succop, S.C. Heffelfinger, D.J. Clegg

    2007-01-01

    Full Text Available Developmental stages of mammary glands influence their susceptibility to initiating events related to carcinogenesis. The “window of susceptibility” to mammary carcinogenesis is classically defined as the time in early puberty when the mammary gland morphology is most sensitive to initiation events. Administration of the polyaromatic hydrocarbon, 7,12-dimethylbenz(aanthracene (DMBA, in a single oral dose yields maximal mammary tumor formation when administered in this “window”. We examined the DMBA treated mammary glands, precursor lesions, and morphology of the uninvolved mammary epithelium for the first 100 days of life for Charles River Sprague Dawley CDR IGS. Our goal was to determine the DMBA dose at which 50% of the rats (IC50 developed carcinoma in situ (CIS within three months of dosing. Here we demonstrate, rather than the classical U-shaped dose curve in which there is maximum sensitivity for DMBA at 50 days, there is an increasing degree of sensitivity with age in the CDR IGS rat. Additionally, we report that vehicle-treated animals developed mammary CIS without any known initiator, and 100 day virgin animals demonstrated lactational changes, independent of DMBA exposure or dose. Lastly, we demonstrate this strain of virgin female rats has elevated pituitary prolactin immunoreactivity independent of the level of mammary differentiation. We conclude this strain of Charles River Sprague Dawley rats has prolactin-induced pituitary stimulation, and therefore, the window of susceptibility for mammary tumorigenesis is absent.

  20. The Role of Insulin-like Growth Factor-I and IGF-binding Proteins in Mammary Gland Development

    Weber, Miriam S

    1998-01-01

    Development of the mammary gland is likely mediated by locally produced growth factors acting in concert with circulating mitogens. To investigate the importance of mammary synthesis of insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGFBP), the initial objective was to evaluate the physiological effects of recombinant IGF-I synthesis in the mouse mammary gland. Expression of recombinant IGF-I was targeted by the mouse mammary tumor virus - long terminal repeat (MMTV-LTR) to ...

  1. The transcription factor ATF3 acts as an oncogene in mouse mammary tumorigenesis

    Thames Howard D

    2008-09-01

    Full Text Available Abstract Background Overexpression of the bZip transcription factor, ATF3, in basal epithelial cells of transgenic mice under the control of the bovine cytokeratin-5 (CK5 promoter has previously been shown to induce epidermal hyperplasia, hair follicle anomalies and neoplastic lesions of the oral mucosa including squamous cell carcinomas. CK5 is known to be expressed in myoepithelial cells of the mammary gland, suggesting the possibility that transgenic BK5.ATF3 mice may exhibit mammary gland phenotypes. Methods Mammary glands from nulliparous mice in our BK5.ATF3 colony, both non-transgenic and transgenic, were examined for anomalies by histopathology and immunohistochemistry. Nulliparous and biparous female mice were observed for possible mammary tumor development, and suspicious masses were analyzed by histopathology and immunohistochemistry. Human breast tumor samples, as well as normal breast tissue, were similarly analyzed for ATF3 expression. Results Transgenic BK5.ATF3 mice expressed nuclear ATF3 in the basal layer of the mammary ductal epithelium, and often developed squamous metaplastic lesions in one or more mammary glands by 25 weeks of age. No progression to malignancy was seen in nulliparous BK5.ATF3 or non-transgenic mice held for 16 months. However, biparous BK5.ATF3 mice developed mammary carcinomas with squamous metaplasia between 6 months and one year of age, reaching an incidence of 67%. Cytokeratin expression in the tumors was profoundly disturbed, including expression of CK5 and CK8 (characteristic of basal and luminal cells, respectively throughout the epithelial component of the tumors, CK6 (potentially a stem cell marker, CK10 (a marker of interfollicular epidermal differentiation, and mIRSa2 and mIRSa3.1 (markers of the inner root sheath of hair follicles. Immunohistochemical studies indicated that a subset of human breast tumors exhibit high levels of nuclear ATF3 expression. Conclusion Overexpression of ATF3 in CK5

  2. Atm heterozygous deficiency enhances development of mammary carcinomas in p53 heterozygous knockout mice

    Ataxia-telangiectasia is an autosomal-recessive disease that affects neuro-immunological functions, associated with increased susceptibility to malignancy, chromosomal instability and hypersensitivity to ionizing radiation. Although ataxia-telangiectasia mutated (ATM) heterozygous deficiency has been proposed to increase susceptibility to breast cancer, some studies have not found excess risk. In experimental animals, increased susceptibility to breast cancer is not observed in the Atm heterozygous deficient mice (Atm+/-) carrying a knockout null allele. In order to determine the effect of Atm heterozygous deficiency on mammary tumourigenesis, we generated a series of Atm+/- mice on the p53+/- background with a certain predisposition to spontaneous development of mammary carcinomas, and we examined the development of the tumours after X-irradiation. BALB/cHeA-p53+/- mice were crossed with MSM/Ms-Atm+/- mice, and females of the F1 progeny ([BALB/cHeA × MSM/Ms]F1) with four genotypes were used in the experiments. The mice were exposed to X-rays (5 Gy; 0.5 Gy/min) at age 5 weeks. We tested the effect of haploinsufficiency of the Atm gene on mammary tumourigenesis after X-irradiation in the p53+/- mice of the BALB/cHeA × MSM/Ms background. The singly heterozygous p53+/- mice subjected to X-irradiation developed mammary carcinomas at around 25 weeks of age, and the final incidence of mammary carcinomas at 39 weeks was 31% (19 out of 61). The introduction of the heterozygous Atm knockout alleles into the background of the p53+/- genotype significantly increased the incidence of mammary carcinoma to 58% (32 out of 55) and increased the average number of mammary carcinomas per mouse. However, introduction of Atm alleles did not change the latency of development of mammary carcinoma. Our results indicate a strong enhancement in mammary carcinogenesis by Atm heterozygous deficiency in p53+/- mice. Thus, doubly heterozygous mice represent a useful model system with which to

  3. The transcription factor ATF3 acts as an oncogene in mouse mammary tumorigenesis

    Overexpression of the bZip transcription factor, ATF3, in basal epithelial cells of transgenic mice under the control of the bovine cytokeratin-5 (CK5) promoter has previously been shown to induce epidermal hyperplasia, hair follicle anomalies and neoplastic lesions of the oral mucosa including squamous cell carcinomas. CK5 is known to be expressed in myoepithelial cells of the mammary gland, suggesting the possibility that transgenic BK5.ATF3 mice may exhibit mammary gland phenotypes. Mammary glands from nulliparous mice in our BK5.ATF3 colony, both non-transgenic and transgenic, were examined for anomalies by histopathology and immunohistochemistry. Nulliparous and biparous female mice were observed for possible mammary tumor development, and suspicious masses were analyzed by histopathology and immunohistochemistry. Human breast tumor samples, as well as normal breast tissue, were similarly analyzed for ATF3 expression. Transgenic BK5.ATF3 mice expressed nuclear ATF3 in the basal layer of the mammary ductal epithelium, and often developed squamous metaplastic lesions in one or more mammary glands by 25 weeks of age. No progression to malignancy was seen in nulliparous BK5.ATF3 or non-transgenic mice held for 16 months. However, biparous BK5.ATF3 mice developed mammary carcinomas with squamous metaplasia between 6 months and one year of age, reaching an incidence of 67%. Cytokeratin expression in the tumors was profoundly disturbed, including expression of CK5 and CK8 (characteristic of basal and luminal cells, respectively) throughout the epithelial component of the tumors, CK6 (potentially a stem cell marker), CK10 (a marker of interfollicular epidermal differentiation), and mIRSa2 and mIRSa3.1 (markers of the inner root sheath of hair follicles). Immunohistochemical studies indicated that a subset of human breast tumors exhibit high levels of nuclear ATF3 expression. Overexpression of ATF3 in CK5-expressing cells of the murine mammary gland results in the

  4. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells

    Notch signaling has been implicated in the regulation of cell-fate decisions such as self-renewal of adult stem cells and differentiation of progenitor cells along a particular lineage. Moreover, depending on the cellular and developmental context, the Notch pathway acts as a regulator of cell survival and cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors. In order to determine the role of Notch signaling in mammary cell-fate determination, we have utilized a newly described in vitro system in which mammary stem/progenitor cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists. Utilizing this system, we demonstrate that Notch signaling can act on mammary stem cells to promote self-renewal and on early progenitor cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notch-activating DSL peptide. In addition to acting on stem cells, Notch signaling is also able to act on multipotent progenitor cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial cells. These studies

  5. High intensity hadron accelerators

    In this paper we give an introductory discussion of high intensity hadron accelerators with special emphasis on the high intensity feature. The topics selected for this discussion are: Types of acclerator - The principal actions of an accelerator are to confine and to accelerate a particle beam. Focusing - This is a discussion of the confinement of single particles. Intensity limitations - These are related to confinement of intense beams of particles. Power economics - Considerations related to acceleration of intense beams of particles. Heavy ion kinematics - The adaptation of accelerators to accelerate all types of heavy ions

  6. The direction of acceleration

    Wilhelm, Thomas; Burde, Jan-Philipp; Lück, Stephan

    2015-11-01

    Acceleration is a physical quantity that is difficult to understand and hence its complexity is often erroneously simplified. Many students think of acceleration as equivalent to velocity, a ˜ v. For others, acceleration is a scalar quantity, which describes the change in speed Δ|v| or Δ|v|/Δt (as opposed to the change in velocity). The main difficulty with the concept of acceleration therefore lies in developing a correct understanding of its direction. The free iOS app AccelVisu supports students in acquiring a correct conception of acceleration by showing acceleration arrows directly at moving objects.

  7. 2014 CERN Accelerator Schools: Plasma Wake Acceleration

    2014-01-01

    A specialised school on Plasma Wake Acceleration will be held at CERN, Switzerland from 23-29 November, 2014.   This course will be of interest to staff and students in accelerator laboratories, university departments and companies working in or having an interest in the field of new acceleration techniques. Following introductory lectures on plasma and laser physics, the course will cover the different components of a plasma wake accelerator and plasma beam systems. An overview of the experimental studies, diagnostic tools and state of the art wake acceleration facilities, both present and planned, will complement the theoretical part. Topical seminars and a visit of CERN will complete the programme. Further information can be found at: http://cas.web.cern.ch/cas/PlasmaWake2014/CERN-advert.html http://indico.cern.ch/event/285444/

  8. Peripheral serotonin regulates maternal calcium trafficking in mammary epithelial cells during lactation in mice.

    Jimena Laporta

    Full Text Available Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood into the ductal lumen (milk. Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1, which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin. As a consequence maternal calcium concentrations decrease, mammary epithelial cell morphology is altered, and cell proliferation is decreased during lactation. Here we demonstrate that serotonin deficiency decreases the expression and disrupts the normal localization of calcium transporters located in the apical (PMCA2 and basolateral (CaSR, ORAI-1 membranes of the lactating mammary gland. In addition, serotonin deficiency decreases the mRNA expression of calcium transporters located in intracellular compartments (SERCA2, SPCA1 and 2. Mammary expression of serotonin receptor isoform 2b and its downstream pathways (PLCβ3, PKC and MAP-ERK1/2 are also decreased by serotonin deficiency, which might explain the numerous phenotypic alterations described above. In most cases, addition of exogenous 5-hydroxy-L-tryptophan to the Tph1 deficient mice rescued the phenotype. Our data supports the hypothesis that serotonin is necessary for proper mammary gland structure and function, to regulate blood and mammary epithelial cell transport of calcium during lactation. These findings can be applicable to the treatment of lactation-induced hypocalcemia in dairy cows and can have profound implications in humans, given the wide-spread use of selective serotonin reuptake inhibitors as antidepressants during pregnancy and lactation.

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

    Stewart, Michael K. G.; Plante, Isabelle; Penuela, Silvia; Laird, Dale W.

    2016-01-01

    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. PMID:27099931

  10. Peripheral serotonin regulates maternal calcium trafficking in mammary epithelial cells during lactation in mice.

    Laporta, Jimena; Keil, Kimberly P; Vezina, Chad M; Hernandez, Laura L

    2014-01-01

    Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood) into the ductal lumen (milk). Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT) is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1), which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin. As a consequence maternal calcium concentrations decrease, mammary epithelial cell morphology is altered, and cell proliferation is decreased during lactation. Here we demonstrate that serotonin deficiency decreases the expression and disrupts the normal localization of calcium transporters located in the apical (PMCA2) and basolateral (CaSR, ORAI-1) membranes of the lactating mammary gland. In addition, serotonin deficiency decreases the mRNA expression of calcium transporters located in intracellular compartments (SERCA2, SPCA1 and 2). Mammary expression of serotonin receptor isoform 2b and its downstream pathways (PLCβ3, PKC and MAP-ERK1/2) are also decreased by serotonin deficiency, which might explain the numerous phenotypic alterations described above. In most cases, addition of exogenous 5-hydroxy-L-tryptophan to the Tph1 deficient mice rescued the phenotype. Our data supports the hypothesis that serotonin is necessary for proper mammary gland structure and function, to regulate blood and mammary epithelial cell transport of calcium during lactation. These findings can be applicable to the treatment of lactation-induced hypocalcemia in dairy cows and can have profound implications in humans, given the wide-spread use of selective serotonin reuptake inhibitors as antidepressants during pregnancy and lactation. PMID:25299122

  11. Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation.

    Mohanty, Sambit K; Kim, Stacey A; DeLair, Deborah F; Bose, Shikha; Laury, Anna R; Chopra, Shefali; Mertens, Richard B; Dhall, Deepti

    2016-08-01

    Metastatic neuroendocrine neoplasms to the breast may show considerable morphologic overlap with primary mammary carcinomas, particularly those showing evidence of neuroendocrine differentiation, and may be misdiagnosed as such. Accurate distinction between these two entities is crucial for determination of appropriate clinical management. The histologic and immunohistochemical features of metastatic neuroendocrine neoplasms to the breast were studied and compared with the features of primary invasive mammary carcinomas with neuroendocrine differentiation, which served as controls. Of the metastatic neuroendocrine neoplasms, 15 were well-differentiated neuroendocrine tumors with carcinoid tumor-type morphology and 7 were poorly differentiated/high-grade neuroendocrine carcinomas with small-cell or large-cell neuroendocrine carcinoma morphology. The majority of the metastatic neoplasms originated in the lung and gastrointestinal tract. There were histologic similarities between metastatic neuroendocrine neoplasms and invasive mammary carcinomas with neuroendocrine differentiation, both of which exhibited neuroendocrine histologic features (nested and trabecular architecture, minimal tubular differentiation, and characteristic nuclear features). Only one case of the invasive mammary carcinomas with neuroendocrine differentiation was modified Bloom-Richardson grade 1 (largely due to minimal tubular differentiation on most such tumors), and the invasive mammary carcinomas with neuroendocrine differentiation were often associated with in situ carcinoma. Immunohistochemistry was helpful in distinguishing metastatic neuroendocrine neoplasms from invasive mammary carcinomas with neuroendocrine differentiation. Whereas the majority of invasive mammary carcinomas with neuroendocrine differentiation were positive for estrogen receptor and GATA3, metastatic neuroendocrine neoplasms were typically negative for estrogen receptor and GATA3, and metastatic well

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

    Mandrup, K; Boberg, J; Isling, L K; Christiansen, S; Hass, U

    2016-07-01

    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 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 was to perform a study robust enough to contribute to the risk assessment of BPA and to elucidate possible biphasic dose-response relationships. We investigated mammary gland effects in the offspring at 22, 100, and 400 days of age. Male offspring showed increased mammary outgrowth on pup day (PD) 22 at 0.025 mg/kg BPA, indicating an increased mammary development at this low dose only. Increased prevalence of intraductal hyperplasia was observed in BPA females exposed to 0.25 mg/kg at PD 400, but not at PD 100, and not at higher or lower doses. The present findings support data from the published literature 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 intraductal hyperplasia in female rats could be associated with an increased risk for developing hyperplastic lesions, which are parallels to early signs of breast neoplasia in women. Collectively, current knowledge on effects of BPA on mammary gland at low doses indicates that highly exposed humans may not be sufficiently protected. PMID:27088260

  13. Triennial Lactation Symposium: Bovine mammary epithelial cell lineages and parenchymal development.

    Ellis, S; Akers, R M; Capuco, A V; Safayi, S

    2012-05-01

    Mammary development proceeds from an aggregation of cells in the ventral ectoderm to the establishment of an elaborate tree of alveoli, ducts, and cisternae. However, despite abundant data on endocrine regulation of ruminant mammary growth, we know comparatively little about cell lineages, expression of differentiation markers, and plasticity in mammary cell phenotype. Histologic analyses have revealed cell populations with distinct histochemical profiles, but functional assessment of cell populations during development has been limited to analysis of proliferation and frequency estimations of morphotypes. The lack of transplantation models, limited availability of validated antibodies with reactivity to bovine antigens, and similar technical challenges have generally hindered the pace of discovery, but the application of new technologies such as laser microdissection, transcriptional profiling, and multispectral image analysis are yielding important clues into bovine mammary cell ontogeny and developmental regulation. Our analyses have shown that prepubertal ovariectomy affects epithelial architecture, increases the proportion of cells expressing the estrogen receptor, and increases myoepithelial cell development, all concomitant with a dramatic reduction in the mass of parenchymal tissue. Our observations point to a dual role for ovarian secretions in the control of not only the rate of epithelial development, but also the nature of the parenchymal development. The balance of stimulus and inhibition pathways cooperatively regulates mammary growth. The increased reliance on objective staining analyses and quantitative approaches will ensure broader repeatability, application, and extension of the findings regarding the impact of the ovary and other regulatory entities and factors. Advances in understanding the ontogeny of mammary epithelial cells, coupled with established and increasing knowledge of endocrine factors affecting mammary development, may yield

  14. Incidental extra-mammary findings in breast MRI

    Aim: To investigate the frequency, distribution, and nature of incidental extra-mammary findings detected with breast MRI. Materials and methods: Incidental findings were defined as unexpected lesions outside the breast, not previously known or suspected at the time of referral. Five hundred consecutive breast MRI studies performed from June 2010 to September 2012 were reviewed in this retrospective study for which the institutional review board granted approval and waived the requirement for informed consent. MRI findings were compared with subsequent diagnostic procedures in order to differentiate benign from malignant lesions. Results: One hundred and thirty-eight incidental findings were found in 107 of the 500 (21.4%) examined patients. The most common site was the liver (61/138; 44.2%), followed by the lung (24/138; 17.4%), mediastinum (22/138; 15.9%), pleural cavity (15/138; 10.9%), bone tissue (9/138; 6.5%), spleen (3/138; 2.2%), major pectoral muscle (3/138; 2.2%), and kidney (1/138; 0.7%). Twenty-five of the 138 (18.1%) incidental findings were confirmed to be malignant, whereas the remaining 113 (81.9%) were benign. Malignant findings were exclusively detected in patients with known breast carcinoma, whereas incidental findings in patients without a history of carcinoma were all benign. Twenty-five of 100 (24.8%) incidental findings among patients with history of breast cancer were malignant. Conclusion: Although many of incidental findings were benign, some were malignant, altering the diagnostic work-up, staging, and treatment. Therefore, it is important to assess the entire field of view carefully for abnormalities when reviewing breast MRI studies. - Highlights: • 500 consecutive breast MRI studies were retrospectively reviewed. • Incidental findings were found in 107/500 (21.4%) of examined patients. • Incidental extra-mammary findings on breast MRI are common. • Malignant findings were exclusively detected in patients with known breast

  15. Construction of a recombinant human insulin expression vector for mammary gland-specific expression in buffalo (Bubalus bubalis) mammary epithelial cell line.

    Kaushik, Ramakant; Singh, Karn Pratap; Kumari, Archana; Rameshbabu, K; Singh, Manoj Kumar; Manik, Radhey Shyam; Palta, Prabhat; Singla, Suresh Kumar; Chauhan, Manmohan Singh

    2014-09-01

    The aim of the present study was construction of mammary gland specific expression vector for high level of human insulin (hINS) expression in transgenic buffalo for therapeutic use. We have constructed mammary gland specific vector containing human insulin gene and there expression efficiency was checked into in vitro cultured buffalo mammary epithelial cells (BuMECs). Human pro-insulin coding region was isolated from human genomic DNA by intron skipping PCR primer and furin cleavage site was inserted between B-C and C-A chain of human insulin by overlap extension PCR. A mammary gland-specific buffalo beta-lactoglobulin promoter was isolated from buffalo DNA and used for human insulin expression in BuMEC cells. The construct was transfected into BuMECs by lipofection method and positive transgene cell clones were obtained by G418 selection after 3 weeks. Expression of hINS in transfected cells were confirmed by RT-PCR, Immunocytochemistry, Western Blotting and ELISA. The pAcISUBC insulin-expressing clones secreted insulin at varying levels between 0.18 - 1.43 ng/ml/24 h/2.0 × 10(6) cells. PMID:24969480

  16. 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.

    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. PMID:27270969

  17. San Francisco Accelerator Conference

    'Where are today's challenges in accelerator physics?' was the theme of the open session at the San Francisco meeting, the largest ever gathering of accelerator physicists and engineers

  18. Dielectric Laser Acceleration

    England, R. Joel; Noble, Robert J.; Wu, Ziran; Qi, Minghao

    2013-01-01

    We describe recent advances in the study of particle acceleration using dielectric near-field structures driven by infrared lasers, which we refer to as Dielectric Laser Accelerators. Implications for high energy physics and other applications are discussed.

  19. Standing wave linear accelerator

    Consideration is being given to standing wave linear accelerator containing generator, phase shifter, two accelerating resonator sections, charged particle injector and waveguide bridge. Its first arm is oined up with generator via the phase shifter, the second and the third ones-with accelerating sections and the fourth one - with HF-power absorber. HF-power absorber represents a section of circular diaphragmatic wavequide with transformer with input wave and intrawaveguide output load located between injector and the first accelerating section. The section possesses holes in side walls lying on accelerator axis. The distances between centers of the last cell of the fast accelerating section and the first cell of the second accelerating sectiOn equal (2n+3)lambda/4, where n=1, 2, 3..., lambda - wave length of generator. The suggested system enables to improve by one order spectral characteristics of accelerators as compared to the prototype in which magnetrons are used as generator

  20. Improved plasma accelerator

    Cheng, D. Y.

    1971-01-01

    Converging, coaxial accelerator electrode configuration operates in vacuum as plasma gun. Plasma forms by periodic injections of high pressure gas that is ionized by electrical discharges. Deflagration mode of discharge provides acceleration, and converging contours of plasma gun provide focusing.

  1. High Energy Particle Accelerators

    Audio Productions, Inc, New York

    1960-01-01

    Film about the different particle accelerators in the US. Nuclear research in the US has developed into a broad and well-balanced program.Tour of accelerator installations, accelerator development work now in progress and a number of typical experiments with high energy particles. Brookhaven, Cosmotron. Univ. Calif. Berkeley, Bevatron. Anti-proton experiment. Negative k meson experiment. Bubble chambers. A section on an electron accelerator. Projection of new accelerators. Princeton/Penn. build proton synchrotron. Argonne National Lab. Brookhaven, PS construction. Cambridge Electron Accelerator; Harvard/MIT. SLAC studying a linear accelerator. Other research at Madison, Wisconsin, Fixed Field Alternate Gradient Focusing. (FFAG) Oakridge, Tenn., cyclotron. Two-beam machine. Comments : Interesting overview of high energy particle accelerators installations in the US in these early years. .

  2. Maximal Acceleration Is Nonrotating

    Page, Don N.

    1997-01-01

    In a stationary axisymmetric spacetime, the angular velocity of a stationary observer that Fermi-Walker transports its acceleration vector is also the angular velocity that locally extremizes the magnitude of the acceleration of such an observer, and conversely if the spacetime is also symmetric under reversing both t and phi together. Thus a congruence of Nonrotating Acceleration Worldlines (NAW) is equivalent to a Stationary Congruence Accelerating Locally Extremely (SCALE). These congruenc...

  3. Accelerators at school

    Latest subject covered by the CERN Accelerator School was 'Applied Geodesy of Particle Accelerators', which attracted an impressive number of outside participants to CERN for a week in April. Since the forerunners of today's particle accelerators were demonstrated over 50 years ago, the positioning of accelerator components has progressed from the laboratory bench-top to tunnels tens of kilometres long. Despite this phenomenal growth in size, sub-millimetre accuracy is still required

  4. A Solid state accelerator

    We present a solid state accelerator concept utilizing particle acceleration along crystal channels by longitudinal electron plasma waves in a metal. Acceleration gradients of order 100 GV/cm are theoretically possible, but channeling radiation limits the maximum attainable energy to 105 TeV for protons. Beam dechanneling due to multiple scattering is substantially reduced by the high acceleration gradient. Plasma wave dissipation and generation in metals are also discussed

  5. Superconducting accelerator technology

    Modern and future accelerators for high energy and nuclear physics rely increasingly on superconducting components to achieve the required magnetic fields and accelerating fields. This paper presents a practical overview of the phenomenon of superconductivity, and describes the design issues and solutions associated with superconducting magnets and superconducting rf acceleration structures. Further development and application of superconducting components promises increased accelerator performance at reduced electric power cost

  6. Applications of particle accelerators

    Particle accelerators are now widely used in a variety of applications for scientific research, applied physics, medicine, industrial processing, while possible utilisation in power engineering is envisaged. Earlier presentations of this subject, given at previous CERN Accelerator School sessions have been updated with papers contributed to the first European Conference on Accelerators in Applied Research and Technology (ECAART) held in September 1989 in Frankfurt and to the Second European Particle Accelerator Conference in Nice in June 1990. (orig.)

  7. The Stat6-regulated KRAB domain zinc finger protein Zfp157 regulates the balance of lineages in mammary glands and compensates for loss of Gata-3

    Oliver, Carrie H.; Khaled, Walid T.; Frend, Hayley; Nichols, Jennifer; Watson, Christine J.

    2012-01-01

    Cell fate specification in mammary stem and progenitor cells is not well understood. In this study by Watson and colleagues, the authors identify a novel transcriptional regulator, Zfp157, as a target of Stat6. The authors demonstrate that Zfp157 regulates mammary progenitor cells by deleting Zfp157 in luminal cells, which resulted in a dramatic shift in the cellular composition of the mammary gland. In addition, the authors found that Gata-3 is not an essential regulator of mammary gland mor...

  8. Culture models of human mammary epithelial cell transformation

    Stampfer, Martha R.; Yaswen, Paul

    2000-11-10

    Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS)3 already display several of the aberrant phenotypes found in primary breast cancers, including chromosomal abnormalities, telomerase activity, inactivation of the p53 gene and overexpression of some oncogenes. Efforts to model early breast carcinogenesis in human cell cultures have largely involved studies in vitro transformation of normal finite lifespan human mammary epithelial cells (HMEC) to immortality and malignancy. We present a model of HMEC immortal transformation consistent with the know in vivo data. This model includes a recently described, presumably epigenetic process, termed conversion, which occurs in cells that have overcome stringent replicative senescence and are thus able to maintain proliferation with critically short telomeres. The conversion process involves reactivation of telomerase activity, and acquisition of good uniform growth in the absence and presence of TFGB. We propose th at overcoming the proliferative constraints set by senescence, and undergoing conversion, represent key rate-limiting steps in human breast carcinogenesis, and occur during early stage breast cancer progression.

  9. Active synthesis of epidermal growth factor in human mammary glands

    Mieczysław Walczak

    2010-06-01

    Full Text Available Background. Human milk contains considerable number of growth factors, including epidermal growth factor (EGF and insulin-like growth factor-1 (IGF-1. There are no data comparing the EGF and IGF-1 levels in the serum and milk of breast-feeding women. Therefore, the aim of our study was to assess a possible relationship between the concentrations of these growth factors. Material and methods. Thirty-nine women in child-birth were included in the study. All women provided blood and milk samples during the first six hours after delivery. EGF (by immunoenzymatic method and IGF-1 (by radioimmunossay method concentrations were measured in both media. Results. EGF breast milk concentrations ranged from 3.18 to 4.51 ng/ml and on average were significantly higher (p < 0.0001 than those found in the women’s serum (from 0.02 to 0.13 ng/ml. The opposite distribution was found for IGF-1 levels. Its milk concentrations ranged from 8.8 to 61.9 ng/ml and on average were significantly lower (p < 0.0001 than the serum concentrations (from 192.6 to 595.3 ng/ml. No correlation was found between the serum and milk concentrations of both growth factors. Conclusion. EGF seems to be synthesized locally in mammary glands, whereas IGF-1 probably permeates into the milk from the vascular bed.  

  10. Influence of colforsin daropate hydrochloride on internal mammary artery grafts.

    Hayashida, Nobuhiko; Teshima, Hideki; Tayama, Eiki; Chihara, Shingo; Enomoto, Naofumi; Kawara, Takemi; Aoyagi, Shigeaki

    2002-04-01

    The effect of colforsin daropate hydrochloride (colforsin), a water-soluble forskolin derivative, on blood flow in internal mammary artery (IMA) grafts was evaluated in a prospective randomized study of 26 patients undergoing coronary artery bypass grafting. Patients were randomized to receive either colforsin treatment (colforsin; n=14) or no colforsin treatment (control; n=14). Administration of colforsin (0.5mg x kg(-1) min(-1)) was started after induction of anesthesia and was continued for 6 h. IMA blood flow and hemodynamic measurements were assessed perioperatively. During cardiopoulmonary bypass (CPB), perfusion flow was adjusted to 2.5 L/m2 and IMA free blood flow was measured. IMA blood flow was also measured 1 h after CPB by an ultrasonic flow meter. Systemic vascular resistance was significantly lower in the colforsin group during and after CPB. IMA blood flow was significantly greater in the colforsin group than in the control group during (44 +/- 2 vs 33 +/- 3 ml min-1 x m(-2), p=0.02) and after CPB (38 +/- 6 vs 20 +/- 3ml x min(-1) m(-2), p=0.01). IMA blood flow 1 h after CPB correlated inversely with concurrent systemic vascular resistance (r=-0.61, p=0.001). Intraoperative administration of colforsin daropate hydrochloride caused potent vasodilation, resulting in an increase in IMA blood flow. The results indicate that the regimen can be used perioperatively in patients undergoing coronary artery bypass grafting. PMID:11954952

  11. Sialomucin and lytic susceptibility of rat mammary tumor ascites cells.

    Moriarty, J; Skelly, C M; Bharathan, S; Moody, C E; Sherblom, A P

    1990-11-01

    The potential role of cell surface sialomucin in preventing natural killer (NK)-mediated lysis of tumor cell targets has been addressed by comparing the properties of 2 NK-resistant [ascites (ASC) and short-term cultured (STC)] and 2 NK-susceptible [tunicamycin-treated (TUN) and long-term cultured (LTC)] preparations of 13762 MAT-B1 rat mammary tumor cells. Both the ASC and STC cell preparations contain elevated levels of the sialomucin ASGP-1 relative to TUN and LTC preparations as determined by [3H]glucosamine labeling and by binding of peanut agglutinin. The major difference in the susceptibility to NK-mediated lysis appeared to be due to the differences in the susceptibility to lysis by lytic granules, rather than to differences in the ability to bind or trigger effector cells, since TUN and LTC cells were approximately 10-fold more sensitive to lysis by lytic granules than were ASC and STC cells. All preparations inhibited the lysis of the susceptible target YAC-1 by normal rat splenocytes, indicating an ability to bind these effector cells. Triggering of effectors, as monitored either by incorporation of 32P into phosphatidylinositol or by transmethylation of phosphatidylcholine, was similar for the positive control YAC-1, STC, TUN, and LTC, whereas ASC appeared to be defective in triggering effectors. These results suggest that tumor sialomucin blocks the final phase of lysis, but not the initial recognition of tumor cells by NK effectors. PMID:2208144

  12. Mammary tuberculosis mimicking breast cancer: a case report

    Maroulis Ioannis

    2008-02-01

    Full Text Available Abstract Introduction The incidence of tuberculosis is rising worldwide and rare manifestations of the past are seen more often nowadays. Mammary tuberculosis is a rare clinical entity, often mimicking breast cancer or abscesses of benign or malignant origin. Clinical awareness is necessary during diagnostic work-up for establishing the correct diagnosis and treatment. Case presentation We present a case of breast tuberculosis diagnosed in a 73 year old woman at our institution. The patient presented with a palpable mass of the right breast with clinical, laboratory and mammographic findings indicative of breast carcinoma. The patient underwent lumpectomy and sentinel lymph node biopsy. Frozen section of the tumor and the sentinel node revealed "granulomatous inflammation", while gross examination confirmed the diagnosis of tuberculous mastitis. The patient received anti-tuberculosis therapy for six months with no side effects or any further complications. Conclusion Breast tuberculosis is an obscure disease often mistaken for carcinoma or pyogenic abscess of the breast, especially if well-defined clinical features are absent. A high index of suspicion is required because the disease can usually be treated conservatively with current antituberculous modalities while surgical intervention is reserved for rare cases only.

  13. Radiation-induced chromosomal instability in human mammary epithelial cells

    Durante, M.; Grossi, G. F.; Yang, T. C.

    1996-01-01

    Karyotypes of human cells surviving X- and alpha-irradiation have been studied. Human mammary epithelial cells of the immortal, non-tumorigenic cell line H184B5 F5-1 M/10 were irradiated and surviving clones isolated and expanded in culture. Cytogenetic analysis was performed using dedicated software with an image analyzer. We have found that both high- and low-LET radiation induced chromosomal instability in long-term cultures, but with different characteristics. Complex chromosomal rearrangements were observed after X-rays, while chromosome loss predominated after alpha-particles. Deletions were observed in both cases. In clones derived from cells exposed to alpha-particles, some cells showed extensive chromosome breaking and double minutes. Genomic instability was correlated to delayed reproductive death and neoplastic transformation. These results indicate that chromosomal instability is a radiation-quality-dependent effect which could determine late genetic effects, and should therefore be carefully considered in the evaluation of risk for space missions.

  14. Accelerator development in BARC

    Charged particle accelerators have played crucial role in the field of both basic and applied sciences. This has been possible because the accelerators have been extensively utilized from unraveling the secrets of nature to diverse applications such as implantation, material modification, medical diagnostics and therapy, nuclear energy and clean air and water. The development of accelerators in BARC can be categorized in two broad categories namely proton and heavy ion based accelerators and electron based accelerators. The heavy ion accelerators with sufficiently high energies are currently being used for conducting frontline nuclear and allied research whereas the electron accelerators are being routinely used for various industrial applications. Recently, there is a strong interest for developing the high energy and high intensity accelerators due to their possibility of effective utilization towards concept of energy amplification (Accelerator Driven System), incineration nuclear waste and transmutation. This talk will discuss details of the accelerator development program in BARC with particular emphasis on the recent development at Low Energy High Intensity Proton Accelerator (LEHIPA) Facility in Ion Accelerator Development Division, BARC. (author)

  15. Far field acceleration

    Far fields are propagating electromagnetic waves far from their source, boundary surfaces, and free charges. The general principles governing the acceleration of charged particles by far fields are reviewed. A survey of proposed field configurations is given. The two most important schemes, Inverse Cerenkov acceleration and Inverse free electron laser acceleration, are discussed in detail

  16. The CERN Accelerator School

    2016-01-01

    Introduction to accelerator physics The CERN Accelerator School: Introduction to Accelerator Physics, which should have taken place in Istanbul, Turkey, later this year has now been relocated to Budapest, Hungary.  Further details regarding the new hotel and dates will be made available as soon as possible on a new Indico site at the end of May.

  17. Accelerators and Dinosaurs

    Turner, Michael Stanley

    2003-01-01

    Using naturally occuring particles on which to research might have made accelerators become extinct. But in fact, results from astrophysics have made accelerator physics even more important. Not only are accelerators used in hospitals but they are also being used to understand nature's inner workings by searching for Higgs bosons, CP violation, neutrino mass and dark matter (2 pages)

  18. Acceleration: It's Elementary

    Willis, Mariam

    2012-01-01

    Acceleration is one tool for providing high-ability students the opportunity to learn something new every day. Some people talk about acceleration as taking a student out of step. In actuality, what one is doing is putting a student in step with the right curriculum. Whole-grade acceleration, also called grade-skipping, usually happens between…

  19. Cdk2-Null Mice Are Resistant to ErbB-2-Induced Mammary Tumorigenesis

    Dipankar Ray

    2011-05-01

    Full Text Available The concept of targeting G1 cyclin-dependent kinases (CDKs in breast cancer treatments is supported by the fact that the genetic ablation of Cdk4 had minimal impacts on normal cell proliferation in majority of cell types, resulting in near-normal mouse development, whereas such loss of Cdk4 completely abrogated ErbB-2/neu-induced mammary tumorigenesis in mice. In most human breast cancer tissues, another G1-regulatory CDK, CDK2, is also hyperactivated by various mechanisms and is believed to be an important therapeutic target. In this report, we provide genetic evidence that CDK2 is essential for proliferation and oncogenesis of murine mammary epithelial cells. We observed that 87% of Cdk2-null mice were protected from ErbB-2-induced mammary tumorigenesis. Mouse embryonic fibroblasts isolated from Cdk2-null mouse showed resistance to various oncogene-induced transformation. Previously, we have reported that hemizygous loss of Cdc25A, the major activator of CDK2, can also protect mice from ErbB-2-induced mammary tumorigenesis [Cancer Res (2007 67(14: 6605–11]. Thus, we propose that CDC25A-CDK2 pathway is critical for the oncogenic action of ErbB-2 in mammary epithelial cells, in a manner similar to Cyclin D1/CDK4 pathway.

  20. Effect of spaying and timing of spaying on survival of dogs with mammary carcinoma.

    Sorenmo, K U; Shofer, F S; Goldschmidt, M H

    2000-01-01

    The risk of developing mammary gland tumors in dogs is significantly decreased by ovariohysterectomy at an early age. However, previous studies have not found a benefit to ovariohysterectomy concurrent with tumor removal in dogs with established mammary gland tumors, suggesting that the progression of these tumors is independent of continued estrogen stimulation. The purpose of this study was to evaluate the effect of spaying and of the timing of spaying on survival in dogs with mammary gland carcinoma. Signalment, spay status and spay age, tumor characteristics, treatment. survival, and cause of death of 137 dogs with mammary gland carcinoma were analyzed. The dogs were classified into 3 groups according to spay status and spay time: intact dogs, dogs spayed less than 2 years before tumor surgery (SPAY 1), and dogs spayed more than 2 years before their tumor surgery (SPAY 2). Dogs in the SPAY 1 group lived significantly longer than dogs in SPAY 2 and intact dogs (median survival of 755 days, versus 301 and 286 days, respectively, P = .02 and .03). After adjusting for differences between the spay groups with regard to age, histologic differentiation, and vascular invasion, SPAY 1 dogs survived 45% longer compared to dogs that were either intact or in the SPAY 2 group (RR = .55; 95% CI .32-.93; P = .03). This study reveals ovariohysterectomy to be an effective adjunct to tumor removal in dogs with mammary gland carcinoma and that the timing of ovariohysterectomy is important in influencing survival. PMID:10830539

  1. Anti-influenza neuraminidase inhibitor oseltamivir phosphate induces canine mammary cancer cell aggressiveness.

    de Oliveira, Joana T; Santos, Ana L; Gomes, Catarina; Barros, Rita; Ribeiro, Cláudia; Mendes, Nuno; de Matos, Augusto J; Vasconcelos, M Helena; Oliveira, Maria José; Reis, Celso A; Gärtner, Fátima

    2015-01-01

    Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor) in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells. Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft of oseltamivir phosphate-treated nude mice showed increased sialylation, namely α2,6 terminal structures and SLe(x) expression. Remarkably, a trend towards increased lung metastases was observed in oseltamivir phosphate-treated nude mice. Taken together, our findings revealed that oseltamivir impairs canine mammary cancer cell sialidase activity, altering the sialylation pattern of canine mammary tumors, and leading, surprisingly, to in vitro and in vivo increased mammary tumor aggressiveness. PMID:25850034

  2. Anti-influenza neuraminidase inhibitor oseltamivir phosphate induces canine mammary cancer cell aggressiveness.

    Joana T de Oliveira

    Full Text Available Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells. Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft of oseltamivir phosphate-treated nude mice showed increased sialylation, namely α2,6 terminal structures and SLe(x expression. Remarkably, a trend towards increased lung metastases was observed in oseltamivir phosphate-treated nude mice. Taken together, our findings revealed that oseltamivir impairs canine mammary cancer cell sialidase activity, altering the sialylation pattern of canine mammary tumors, and leading, surprisingly, to in vitro and in vivo increased mammary tumor aggressiveness.

  3. Global Changes in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2

    Bhupinder Pal

    2013-02-01

    Full Text Available The mammary epithelium is a dynamic, highly hormone-responsive tissue. To explore chromatin modifications underlying its lineage specification and hormone responsiveness, we determined genome-wide histone methylation profiles of mammary epithelial subpopulations in different states. The marked differences in H3K27 trimethylation between subpopulations in the adult gland suggest that epithelial cell-fate decisions are orchestrated by polycomb-complex-mediated repression. Remarkably, the mammary epigenome underwent highly specific changes in different hormonal contexts, with a profound change being observed in the global H3K27me3 map of luminal cells during pregnancy. We therefore examined the role of the key H3K27 methyltransferase Ezh2 in mammary physiology. Its expression and phosphorylation coincided with H3K27me3 modifications and peaked during pregnancy, driven in part by progesterone. Targeted deletion of Ezh2 impaired alveologenesis during pregnancy, preventing lactation, and drastically reduced stem/progenitor cell numbers. Taken together, these findings reveal that Ezh2 couples hormonal stimuli to epigenetic changes that underpin progenitor activity, lineage specificity, and alveolar expansion in the mammary gland.

  4. Histological and Morphometric Study of Regressive Changes in the Mammary Glands of Pigs during Regression

    Svätoslav Hluchý

    2011-10-01

    Full Text Available The work deals with the histological and morphometric description of regressive changes in the mammary glands of swine after lactation. Samples of mammary glands of thoracic, abdominal and pubic udders were taken soon after they were killed. Samples were processed by histological and histochemical methods and evaluated by subjective and quantitative morphometrical methods. It was found that post-lactation increases the relative volume of connective stroma up to 75.10 ± 14.76 % of collagen in the tissue falls to 74.13 ± 14.87 % and the loose connective tissue, which was part of glandular parenchyma lobules accounts for only 0.97 ± 2.13%. Adipose tissue is 18.93 ± 14.93% of the udders volume.. Relative of glandular parenchyma fell to 5.97 ± 4.95% and mainly consists of a interlobular and lobar ducts and atrophic alveoli. Epithelium is generally in the mammary glands 4.22 ± 3.56% and lumen 1.75 ±1.81%. 1 cm3 of tissue in the mammary glands located 190745.52 tubuloalveolar structures. Alveoli reach an average size of 36.80 ± 11.57 μm. It was found relative volume of the walls (epithelium and cavities (lumen of each alveolus, the amount of epithelial cells and the nucleocytoplasmic ratio. The individual building components mammary glands were calculated correlation relations.

  5. Janus Kinase 1 Is Essential for Inflammatory Cytokine Signaling and Mammary Gland Remodeling.

    Sakamoto, Kazuhito; Wehde, Barbara L; Yoo, Kyung Hyun; Kim, Taemook; Rajbhandari, Nirakar; Shin, Ha Youn; Triplett, Aleata A; Rädler, Patrick D; Schuler, Fabian; Villunger, Andreas; Kang, Keunsoo; Hennighausen, Lothar; Wagner, Kay-Uwe

    2016-06-01

    Despite a wealth of knowledge about the significance of individual signal transducers and activators of transcription (STATs), essential functions of their upstream Janus kinases (JAKs) during postnatal development are less well defined. Using a novel mammary gland-specific JAK1 knockout model, we demonstrate here that this tyrosine kinase is essential for the activation of STAT1, STAT3, and STAT6 in the mammary epithelium. The loss of JAK1 uncouples interleukin-6-class ligands from their downstream effector, STAT3, which leads to the decreased expression of STAT3 target genes that are associated with the acute-phase response, inflammation, and wound healing. Consequently, JAK1-deficient mice exhibit impaired apoptosis and a significant delay in mammary gland remodeling. Using RNA sequencing, we identified several new JAK1 target genes that are upregulated during involution. These include Bmf and Bim, which are known regulators of programmed cell death. Using a BMF/BIM-double-knockout epithelial transplant model, we further validated that the synergistic action of these proapoptotic JAK1 targets is obligatory for the remodeling of the mammary epithelium. The collective results of this study suggest that JAK1 has nonredundant roles in the activation of particular STAT proteins and this tyrosine kinase is essential for coupling inflammatory cytokine signals to the cell death machinery in the differentiated mammary epithelium. PMID:27044867

  6. Adipose triglyceride lipase regulates lipid metabolism in dairy goat mammary epithelial cells.

    Li, Jun; Luo, Jun; Wang, Hui; Shi, Hengbo; Zhu, Jiangjiang; Sun, Yuting; Yu, Kang; Yao, Dawei

    2015-01-01

    Adipose triglyceride lipase (ATGL) catalyzes the initial step in the lipid lipolysis process, hydrolyzing triglyceride (TG) to produce diacylglycerol (DG) and free fatty acids (FFA). In addition, ATGL regulates lipid storage and release in adipocyte cells. However, its role in mammary gland tissue remains unclear. To assess the role of the ATGL gene in the goat mammary gland, this study analyzed the tissue distribution and expression of key genes together with lipid accumulation after knockdown of the ATGL gene. The mRNA of ATGL was highly expressed in subcutaneous adipose tissue, the lung and the mammary gland with a significant increase in expression during the lactation period compared with the dry period of the mammary gland. Knockdown of the ATGL gene in goat mammary epithelial cells (GMECs) using siRNA resulted in a significant decrease in both ATGL mRNA and protein levels. Silencing of the ATGL gene markedly increased lipid droplet accumulation and intracellular TG concentration (Pfat formation and secretion was down-regulated (PCD36 for fatty acid uptake (P<0.05). In conclusion, these data suggest that the ATGL gene plays an important role in triglyceride lipolysis in GMECs and provides the first experimental evidence that ATGL may be involved in lipid metabolism during lactation. PMID:25307872

  7. Survey radiography and computerized tomography imaging of the thorax in female dogs with mammary tumors

    Giordano Tatiana

    2010-03-01

    Full Text Available Abstract Background Accurate early diagnosis of lung metastases is important for establishing therapeutic measures. Therefore, the present study aimed to compare survey thoracic radiographs and computerized tomography (CT scans to specifically identify lung metastases in female dogs with mammary tumors. Methods Twenty-one female dogs, weighing 3 to 34 kg and aged from 5 years to 14 years and 10 months, with mammary tumors were studied. In all dogs before the imaging examinations, fine-needle aspiration cytology of the mammary tumors was performed to confirm the diagnosis. Three-view thoracic radiographs were accomplished: right lateral, left lateral and ventrodorsal views. Sequential transverse images of the thorax were acquired on a spiral Scanner, before and after intravenous bolus injection of nonionic iodine contrast. Soft-tissue and lung windows were applied. All the mammary tumors were surgically removed and examined histologically. Results The correlation between the cytological and histological results regarding presence of malignancy was observed in only 17 cases. In radiographic examinations, no dog displayed signs of lung metastases or thorax chest lesions. CT detected lung metastasis in two cases, while small areas of lung atelectasis located peripherally were found in 28.57% of the dogs. Conclusion In this study population, spiral CT showed higher sensitivity than chest radiographies to detect lung metastasis; this indicates that CT should be performed on all female dogs with malignant mammary tumors.

  8. Estrogen receptor coregulators and pioneer factors: The orchestrators of mammary gland cell fate and development

    Bramanandam eManavathi

    2014-08-01

    Full Text Available The 17-beta estradiol (E2, a steroid hormone, which play critical role in various cellular processes such as cell proliferation, differentiation, migration and apoptosis, is essential for reproduction and mammary gland development. E2 actions are mediated by two classical nuclear hormone receptors, estrogen receptor alpha and beta (ERs. The activity of ERs depends on the coordinate activity of ligand binding, posttranslational modification, and importantly their interaction with their partner proteins called ‘coregulators’. Because majority of breast cancers are ERalpha positive and coregulators are proved to be crucial for ER transcriptional activity, an increased interest in the field has led to the identification of a large number of coregulators. In the last decade, gene knockout studies using mouse models provided impetus to our further understanding of the role of these coregulators in mammary gland development. Several coregulators appear to be critical for terminal end bud formation, ductal branching and alveologenesis during mammary gland development. The emerging studies support that, in addition to these coregulators, the other ER partner proteins ‘pioneering factors’ also seems to contribute significantly to E2 signaling and mammary cell fate. This review discusses emerging themes in coregulator- and pioneering factor-mediated action on ER functions, particularly their role in mammary gland cell fate and development.

  9. In vitro culture and characterization of a mammary epithelial cell line from Chinese Holstein dairy cow.

    Han Hu

    Full Text Available BACKGROUND: The objective of this study was to establish a culture system and elucidate the unique characteristics of a bovine mammary epithelial cell line in vitro. METHODOLOGY: Mammary tissue from a three year old lactating dairy cow (ca. 100 d relative to parturition was used as a source of the epithelial cell line, which was cultured in collagen-coated tissue culture dishes. Fibroblasts and epithelial cells successively grew and extended from the culturing mammary tissue at the third day. Pure epithelial cells were obtained by passages culture. PRINCIPAL FINDINGS: The strong positive immunostaining to cytokeratin 18 suggested that the resulting cell line exhibited the specific character of epithelial cells. Epithelial cells cultured in the presence of 10% FBS, supraphysiologic concentrations of insulin, and hydrocortisone maintained a normal diploid chromosome modal number of 2n=60. Furthermore, they were capable of synthesizing beta-casein (CSN2, acetyl-CoA carboxylase-alpha (ACACA and butyrophilin (BTN1A1. An important finding was that frozen preservation in a mixture of 90% FBS and 10% DMSO did not influence the growth characteristics, chromosome number, or protein secretion of the isolated epithelial cell line. CONCLUSIONS: The obtained mammary epithelial cell line had normal morphology, growth characteristics, cytogenetic and secretory characteristics, thus, it might represent an useful tool for studying the function of Chinese Holstein dairy cows mammary epithelial cell (CMECs.

  10. Paracrine-acting adiponectin promotes mammary epithelial differentiation and synergizes with genistein to enhance transcriptional response to estrogen receptor beta signaling

    Mammary stromal adipocytes constitute an active site for the synthesis of the adipokine adiponectin (APN) that may influence the mammary epithelial microenvironment. The relationship between 'local', mammary tissue-derived APN and breast cancer risk is poorly understood. Herein, we identify a novel ...

  11. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

    Simian, M.; Harail, Y.; Navre, M.; Werb, Z.; Lochter, A.; Bissell, M.J.

    2002-03-06

    The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland.

  12. Of humans and canines: Immunohistochemical analysis of PCNA, Bcl-2, p53, cytokeratin and ER in mammary tumours.

    Kumaraguruparan, R; Prathiba, D; Nagini, S

    2006-10-01

    Mammary tumours are the most common neoplasms in humans and canines. Human and canine mammary tumours share several important epidemiological, clinicopathological and biochemical features. Development of mammary tumours involves accumulation of mutant cells caused by excessive proliferation and insufficient apoptosis or dysregulation of cellular differentiation. The present study was therefore designed to investigate the expression of proliferation, differentiation, and apoptosis associated proteins together with expression of estrogen receptors (ER) in both human and canine mammary tumours. Thirty breast cancer patients categorized as pre- and postmenopausal, and 30 mammary gland tumours obtained from bitches were included in this study. The expression of proliferating cell nuclear antigen (PCNA), Bcl-2, p53, cytokeratin and ER in tumour tissues and adjacent tissues were investigated using immunohistochemical staining. While the expression of PCNA, Bcl-2, p53 and ER was significantly increased, expression of cytokeratin was significantly lower in both human as well as canine mammary tumours compared to corresponding adjacent tissues. The magnitude of the changes was however more pronounced in premenopausal patients compared to postmenopausal patients. The changes in proliferation, apoptosis and differentiation associated proteins in human and canine mammary tumours validate use of the canine model to understand the molecular mechanisms of mammary carcinogenesis. PMID:16740286

  13. Embryonic stem cells are redirected to non-tumorigenic epithelial cell fate by interaction with the mammary microenvironment.

    Corinne A Boulanger

    Full Text Available Experiments were conducted to redirect mouse Embryonic Stem (ES cells from a tumorigenic phenotype to a normal mammary epithelial phenotype in vivo. Mixing LacZ-labeled ES cells with normal mouse mammary epithelial cells at ratios of 1:5 and 1:50 in phosphate buffered saline and immediately inoculating them into epithelium-divested mammary fat pads of immune-compromised mice accomplished this. Our results indicate that tumorigenesis occurs only when normal mammary ductal growth is not achieved in the inoculated fat pads. When normal mammary gland growth occurs, we find ES cells (LacZ+ progeny interspersed with normal mammary cell progeny in the mammary epithelial structures. We demonstrate that these progeny, marked by LacZ expression, differentiate into multiple epithelial subtypes including steroid receptor positive luminal cells and myoepithelial cells indicating that the ES cells are capable of epithelial multipotency in this context but do not form teratomas. In addition, in secondary transplants, ES cell progeny proliferate, contribute apparently normal mammary progeny, maintain their multipotency and do not produce teratomas.

  14. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

    The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland

  15. The Accelerator Reliability Forum

    Lüdeke, Andreas; Giachino, R

    2014-01-01

    A high reliability is a very important goal for most particle accelerators. The biennial Accelerator Reliability Workshop covers topics related to the design and operation of particle accelerators with a high reliability. In order to optimize the over-all reliability of an accelerator one needs to gather information on the reliability of many different subsystems. While a biennial workshop can serve as a platform for the exchange of such information, the authors aimed to provide a further channel to allow for a more timely communication: the Particle Accelerator Reliability Forum [1]. This contribution will describe the forum and advertise it’s usage in the community.

  16. Direct Laser Acceleration in Laser Wakefield Accelerators

    Shaw, Jessica

    2016-01-01

    In this dissertation, the direct laser acceleration (DLA) of ionization-injected electrons in a laser wakefield accelerator (LWFA) operating in the quasi-blowout regime has been investigated through experiment and simulation. In the blowout regime of LWFA, the radiation pressure of an intense laser pulse can push a majority of the plasma electrons out and around the main body of the pulse. The expelled plasma electrons feel the electrostatic field of the relatively-stationary ions and are t...

  17. Elevation of miR-221 and -222 in the internal mammary arteries of diabetic subjects and normalization with metformin.

    Coleman, Chasity B; Lightell, Daniel J; Moss, Stephanie C; Bates, Michael; Parrino, Patrick E; Woods, T Cooper

    2013-07-15

    Diabetes is a major risk factor for cardiovascular disease and is associated with increased intimal thickening and accelerated vascular smooth muscle cell (VSMC) proliferation. We measured the expression of two microRNAs that promote intimal thickening, miR-221/222, and mRNA encoding a downstream target, p27(Kip1), in internal mammary artery (IMA) segments collected from 37 subjects undergoing coronary artery bypass grafting. The segments were stratified into three groups: non-diabetic subjects (ND), diabetic subjects not on metformin (DMMet-), and diabetic subjects on metformin (DMMet+). The DMMet- group exhibited a significant increase in miR-221/222 and decrease in p27(Kip1) mRNA compared to both the ND and DMMet+ groups. miR-221/222 levels inversely correlated with metformin dose. VSMCs isolated from the IMAs of the DMMet- group proliferate at a faster rate than those of the ND and DMMet+ groups. Further studies into the importance of miR-221/222 in the increased intimal thickening observed in diabetic subjects is warranted. PMID:23648338

  18. Sequential imaging of indium-111-labeled monoclonal antibody in human mammary tumors hosted in nude mice

    Using a bifunctional chelating agent, indium-111 was attached to a monoclonal antibody 10-3D2, specific for a 126-kilodalton phosphoglycoprotein antigen associated with human mammary carcinoma, and was then used to localize and visualize human mammary tumors hosted in nude mice. Simultaneous tumor concentration of In-111-10-3D2 was eight times greater than that of control I-125-MOPC-21. Uptake of F(ab')2 and Fab of 10-3D2 was also compared. The scintigrams demonstrated that intact antibody provided the best images. Control In-111-labeled MOPC-21 and plasma did not show specific localization in the tumor. Uptake of In-111-labeled 10-3D2 was also compared in two lines of human mammary tumors, BT-20 and HS-578T. Imaging with 10-3D2 was better for BT-20 than for HS-578T

  19. Correlations between nuclear and fluorescent Imaging of mammary tumors in mice

    Carroll, Robin; Stone, John; Blue, Eric; Bradley, Eric; Qian, Jianguo; Saha, Margaret; Welsh, Robert

    2008-10-01

    Progress with new imaging technologies permits the study of biological processes both in vivo and noninvasively. Two systems, a position-sensitive gamma camera and a cooled-CCD camera have been applied in this work. A C3H strain of mouse carrying the Mouse Mammary Tumor Virus (MMTV) was imaged using 800 nm Q-tracker fluorescent dots conjugated to a peptide targeting integrin αυβ C a mammary marker for angiogenesis. We subsequently imaged with the gamma camera to detect low levels of ^125I distribution, and hence, the activity of a trans-membrane protein called the sodium iodide symporter (NIS) responsible for iodine transport. Preliminary results indicate that the biodistribution of the tagged Q-tracker dots and ^125I co-localize very early in seemingly normal mammary glands of infected MMTV mice, while in larger palpable tumors the Q-dot signals are less apparent in comparison with the^125I signal.

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

    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. PMID:26910307