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Sample records for c-myc transactomes mapped

  1. Time-dependent c-Myc transactomes mapped by Array-based nuclear run-on reveal transcriptional modules in human B cells.

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    Jinshui Fan

    Full Text Available BACKGROUND: The definition of transcriptional networks through measurements of changes in gene expression profiles and mapping of transcription factor binding sites is limited by the moderate overlap between binding and gene expression changes and the inability to directly measure global nuclear transcription (coined "transactome". METHODOLOGY/PRINCIPAL FINDINGS: We developed a method to measure nascent nuclear gene transcription with an Array-based Nuclear Run-On (ANRO assay using commercial microarray platforms. This strategy provides the missing component, the transactome, to fully map transcriptional networks. ANRO measurements in an inducible c-Myc expressing human P493-6 B cell model reveals time-dependent waves of transcription, with a transactome early after c-Myc induction that does not persist at a late, steady-state phase, when genes that are regulated by c-Myc and E2F predominate. Gene set matrix analysis further uncovers functionally related groups of genes putatively regulated by waves of transcription factor motifs following Myc induction, starting with AP1 and CREB that are followed by EGR1, NFkB and STAT, and ending with E2F, Myc and ARNT/HIF motifs. CONCLUSIONS/SIGNIFICANCE: By coupling ANRO with previous global mapping of c-Myc binding sites by chromatin immunoprecipitation (ChIP in P493-6 cells, we define a set of transcriptionally regulated direct c-Myc target genes and pave the way for the use of ANRO to comprehensively map any transcriptional network.

  2. The c-Myc Transactivation Domain Is a Direct Modulator of Apoptotic versus Proliferative Signals

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    Chang, David W.; Claassen, Gisela F.; Hann, Stephen R.; Cole, Michael D.

    2000-01-01

    We have assayed the oncogenic, proliferative, and apoptotic activities of the frequent mutations that occur in the c-myc gene in Burkitt's lymphomas. Some alleles have a modest (50 to 60%) increase in transforming activity; however, the most frequent Burkitt's lymphoma allele (T58I) had an unexpected substantial decrease in transforming activity (85%). All alleles restored the proliferation function of c-Myc in cells that grow slowly due to a c-myc knockout. There was discordance for some alleles between apoptotic and oncogenic activities, but only the T58A allele had elevated transforming activity with a concomitant reduced apoptotic potential. We discovered a novel missense mutation, MycS71F, that had a very low apoptotic activity compared to wild-type Myc, yet this mutation has never been found in lymphomas, suggesting that there is no strong selection for antiapoptotic c-Myc alleles. MycS71F also induced very low levels of cytochrome c release from mitochondria, suggesting a mechanism of action for this mutation. Phosphopeptide mapping provided a biochemical basis for the dramatically different biological activities of the transformation-defective T58I and transformation-enhanced T58A c-Myc alleles. Furthermore, the antiapoptotic survival factor insulin-like growth factor 1 was found to suppress phosphorylation of T58, suggesting that the c-Myc transactivation domain is a direct target of survival signals. PMID:10825194

  3. c-myc null cells misregulate cad and gadd45 but not other proposed c-Myc targets

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    Bush, Andrew; Mateyak, Maria; Dugan, Kerri; Obaya, Alvaro; Adachi, Susumu; Sedivy, John; Cole, Michael

    1998-01-01

    We report here that the expression of virtually all proposed c-Myc target genes is unchanged in cells containing a homozygous null deletion of c-myc. Two noteworthy exceptions are the gene cad, which has reduced log phase expression and serum induction in c-myc null cells, and the growth arrest gene gadd45, which is derepressed by c-myc knockout. Thus, cad and gadd45 are the only proposed targets of c-Myc that may contribute to the dramatic slow growth phenotype of c-myc null cells. Our results demonstrate that a loss-of-function approach is critical for the evaluation of potential c-Myc target genes. PMID:9869632

  4. Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility

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    Nunes Virginia

    2008-01-01

    Full Text Available Abstract Background Germline genetic variation is associated with the differential expression of many human genes. The phenotypic effects of this type of variation may be important when considering susceptibility to common genetic diseases. Three regions at 8q24 have recently been identified to independently confer risk of prostate cancer. Variation at 8q24 has also recently been associated with risk of breast and colorectal cancer. However, none of the risk variants map at or relatively close to known genes, with c-MYC mapping a few hundred kilobases distally. Results This study identifies cis-regulators of germline c-MYC expression in immortalized lymphocytes of HapMap individuals. Quantitative analysis of c-MYC expression in normal prostate tissues suggests an association between overexpression and variants in Region 1 of prostate cancer risk. Somatic c-MYC overexpression correlates with prostate cancer progression and more aggressive tumor forms, which was also a pathological variable associated with Region 1. Expression profiling analysis and modeling of transcriptional regulatory networks predicts a functional association between MYC and the prostate tumor suppressor KLF6. Analysis of MYC/Myc-driven cell transformation and tumorigenesis substantiates a model in which MYC overexpression promotes transformation by down-regulating KLF6. In this model, a feedback loop through E-cadherin down-regulation causes further transactivation of c-MYC. Conclusion This study proposes that variation at putative 8q24 cis-regulator(s of transcription can significantly alter germline c-MYC expression levels and, thus, contribute to prostate cancer susceptibility by down-regulating the prostate tumor suppressor KLF6 gene.

  5. c-Myc regulates cell proliferation during lens development.

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    Gabriel R Cavalheiro

    Full Text Available Myc protooncogenes play important roles in the regulation of cell proliferation, growth, differentiation and survival during development. In various developing organs, c-myc has been shown to control the expression of cell cycle regulators and its misregulated expression is detected in many human tumors. Here, we show that c-myc gene (Myc is highly expressed in developing mouse lens. Targeted deletion of c-myc gene from head surface ectoderm dramatically impaired ocular organogenesis, resulting in severe microphtalmia, defective anterior segment development, formation of a lens stalk and/or aphakia. In particular, lenses lacking c-myc presented thinner epithelial cell layer and growth impairment that was detectable soon after its inactivation. Defective development of c-myc-null lens was not caused by increased cell death of lens progenitor cells. Instead, c-myc loss reduced cell proliferation, what was associated with an ectopic expression of Prox1 and p27(Kip1 proteins within epithelial cells. Interestingly, a sharp decrease in the expression of the forkhead box transcription factor Foxe3 was also observed following c-myc inactivation. These data represent the first description of the physiological roles played by a Myc family member in mouse lens development. Our findings support the conclusion that c-myc regulates the proliferation of lens epithelial cells in vivo and may, directly or indirectly, modulate the expression of classical cell cycle regulators in developing mouse lens.

  6. Interaction of c-Myc with the pRb-related protein p107 results in inhibition of c-Myc-mediated transactivation

    NARCIS (Netherlands)

    Beijersbergen, R.L.; Hijmans, E.M.; Zhu, L.; Bernards, R.A.

    1994-01-01

    The product of the c-myc proto-oncogene, c-Myc, is a sequence-specific DNA binding protein with an Nterminal transactivation domain and a C-terminal DNA binding domain. Several lines of evidence indicate that c-Myc activity is essential for normal cell cycle progression. Since the abundance of c-Myc

  7. Global regulation of nucleotide biosynthetic genes by c-Myc.

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    Yen-Chun Liu

    Full Text Available BACKGROUND: The c-Myc transcription factor is a master regulator and integrates cell proliferation, cell growth and metabolism through activating thousands of target genes. Our identification of direct c-Myc target genes by chromatin immunoprecipitation (ChIP coupled with pair-end ditag sequencing analysis (ChIP-PET revealed that nucleotide metabolic genes are enriched among c-Myc targets, but the role of Myc in regulating nucleotide metabolic genes has not been comprehensively delineated. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that the majority of genes in human purine and pyrimidine biosynthesis pathway were induced and directly bound by c-Myc in the P493-6 human Burkitt's lymphoma model cell line. The majority of these genes were also responsive to the ligand-activated Myc-estrogen receptor fusion protein, Myc-ER, in a Myc null rat fibroblast cell line, HO.15 MYC-ER. Furthermore, these targets are also responsive to Myc activation in transgenic mouse livers in vivo. To determine the functional significance of c-Myc regulation of nucleotide metabolism, we sought to determine the effect of loss of function of direct Myc targets inosine monophosphate dehydrogenases (IMPDH1 and IMPDH2 on c-Myc-induced cell growth and proliferation. In this regard, we used a specific IMPDH inhibitor mycophenolic acid (MPA and found that MPA dramatically inhibits c-Myc-induced P493-6 cell proliferation through S-phase arrest and apoptosis. CONCLUSIONS/SIGNIFICANCE: Taken together, these results demonstrate the direct induction of nucleotide metabolic genes by c-Myc in multiple systems. Our finding of an S-phase arrest in cells with diminished IMPDH activity suggests that nucleotide pool balance is essential for c-Myc's orchestration of DNA replication, such that uncoupling of these two processes create DNA replication stress and apoptosis.

  8. Transcriptional regulation of Wnt inhibitory factor-1 by Miz-1/c-Myc

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    Licchesi, JDF; Van Neste, L; Tiwari, VK; Cope, L; Lin, X.; Baylin, SB; Herman, JG

    2010-01-01

    The Wnt signaling pathway is capable of self-regulation through positive and negative feedback mechanisms. For example, the oncoprotein c-Myc, which is upregulated by Wnt signaling activity, participates in a positive feedback loop of canonical Wnt signaling through repression of Wnt antagonists DKK1 and SFRP1. In this study, we investigated the mechanism of Wnt inhibitory factor-1 (WIF-1) silencing. Mapping of CpG island methylation of the WIF-1 promoter reveals regional methylation (–295 to...

  9. Alteraciones del gen c-Myc en la oncogénesis = c-Myc gene alterations in oncogenesis

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    Ospina Pérez, Mariano

    2011-12-01

    Full Text Available La familia de protooncogenes MYC (c-Myc, N-Myc y L-Myc se relaciona con el origen de diversas neoplasias en seres humanos. Estos genes actúan como factores de transcripción y participan en la regulación del ciclo celular, la proliferación y diferenciación celulares, la apoptosis y la inmortalización. Los genes MYC se expresan en diferentes tejidos y responden a diversas señales internas y externas; codifican para la síntesis de factores de transcripción que se unen al ADN para regular la expresión de múltiples genes. El gen más ampliamente estudiado de esta familia es c-Myc, que se expresa en las células con mayor tasa de proli­feración. C-Myc se encuentra alterado en un gran número de tumores sólidos, leucemias y linfomas. Las alteraciones de c-Myc encontradas con mayor frecuencia en células cancero­sas son las amplificaciones, translocaciones, mutaciones y reordenamientos cromosómicos que involucran el locus de este gen y conducen a que se desregule su expresión en diversas neoplasias humanas. La amplificación de c-Myc es una alteración común en los cánceres de mama, pulmón, ovario y próstata, así como en leucemias y linfomas, mientras que la pérdida de su regulación es común en el cáncer de colon, en tumores ginecológicos y melanoma. En neoplasias con defectos de c-Myc los estudios actuales están dirigidos al desarrollo de nuevas estrategias terapéuticas.

  10. Functional analysis of Burkitt's lymphoma mutant c-Myc proteins

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    Smith-Sørensen, B.; Hijmans, E.M.; Bernards, R.A.

    1996-01-01

    The c-myc gene encodes a sequence-specific DNA binding protein that activates transcription of cellular genes. Transcription activation by Myc proteins is regulated by phosphorylation of serine and threonine residues within the transactivation domain and by complex formation with the retinoblastoma-

  11. Postnatal liver growth and regeneration are independent of c-myc in a mouse model of conditional hepatic c-myc deletion

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    Sanders Jennifer A

    2012-03-01

    Full Text Available Abstract Background The transcription factor c-myc regulates genes involved in hepatocyte growth, proliferation, metabolism, and differentiation. It has also been assigned roles in liver development and regeneration. In previous studies, we made the unexpected observation that c-Myc protein levels were similar in proliferating fetal liver and quiescent adult liver with c-Myc displaying nucleolar localization in the latter. In order to investigate the functional role of c-Myc in adult liver, we have developed a hepatocyte-specific c-myc knockout mouse, c-mycfl/fl;Alb-Cre. Results Liver weight to body weight ratios were similar in control and c-myc deficient mice. Liver architecture was unaffected. Conditional c-myc deletion did not result in compensatory induction of other myc family members or in c-Myc's binding partner Max. Floxed c-myc did have a negative effect on Alb-Cre expression at 4 weeks of age. To explore this relationship further, we used the Rosa26 reporter line to assay Cre activity in the c-myc floxed mice. No significant difference in Alb-Cre activity was found between control and c-mycfl/fl mice. c-myc deficient mice were studied in a nonproliferative model of liver growth, fasting for 48 hr followed by a 24 hr refeeding period. Fasting resulted in a decrease in liver mass and liver protein, both of which recovered upon 24 h of refeeding in the c-mycfl/fl;Alb-Cre animals. There was also no effect of reducing c-myc on recovery of liver mass following 2/3 partial hepatectomy. Conclusions c-Myc appears to be dispensable for normal liver growth during the postnatal period, restoration of liver mass following partial hepatectomy and recovery from fasting.

  12. Deubiquitinating c-Myc: USP36 steps up in the nucleolus.

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    Sun, Xiao-Xin; Sears, Rosalie C; Dai, Mu-Shui

    2015-01-01

    Ubiquitination plays a key and complex role in the regulation of c-Myc stability, transactivation, and oncogenic activity. c-Myc is ubiquitinated by a number of ubiquitin ligases (E3s), such as SCF(Fbw7) and SCF(Skp2). Depending on the E3s, ubiquitination can either positively or negatively regulate c-Myc levels and activity. Meanwhile, c-Myc ubiquitination can be reversed by deubiquitination. An early study showed that USP28 deubiquitinates c-Myc via interacting with Fbw7α whereas a recent study reveals that USP37 deubiquitinates c-Myc independently of Fbw7 and c-Myc phosphorylation. Consequently, both USP28 and USP37 stabilize c-Myc and enhance its activity. We recently found the nucleolar USP36 as a novel c-Myc deubiquitinase that controls the end-point of c-Myc degradation pathway in the nucleolus. Here we briefly review the current understanding of ubiquitination and deubiquitination regulation of c-Myc and further discuss the USP36-c-Myc regulatory pathway.

  13. Ezrin mediates c-Myc actions in prostate cancer cell invasion

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    Chuan, Yin Choy; Iglesias Gato, Diego; Fernandez-Perez, L;

    2010-01-01

    The forced overexpression of c-Myc in mouse prostate and in normal human prostate epithelial cells results in tumor transformation with an invasive phenotype. How c-Myc regulates cell invasion is poorly understood. In this study, we have investigated the interplay of c-Myc and androgens in the re...

  14. Upregulation of the oncogene c-myc in Barrett’s adenocarcinoma: induction of c-myc by acidified bile acid in vitro

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    Tselepis, C; C. D. Morris; Wakelin, D; Hardy, R; Perry, I.; Luong, Q T; Harper, E.; Harrison, R.; Attwood, S E A; Jankowski, J.A.Z.

    2003-01-01

    Background and aims: C-myc over expression is implicated in malignancy although to date this has not been studied in Barrett’s metaplasia. We sought to determine c-myc expression in the malignant progression of Barrett’s metaplasia and whether it may be induced by bile acids seen in gastro-oesophageal refluxate.

  15. Upregulation of c-MYC in cis through a Large Chromatin Loop Linked to a Cancer Risk-Associated Single-Nucleotide Polymorphism in Colorectal Cancer Cells▿

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    Wright, Jason B.; Brown, Seth J.; Cole, Michael D.

    2010-01-01

    Genome-wide association studies have mapped many single-nucleotide polymorphisms (SNPs) that are linked to cancer risk, but the mechanism by which most SNPs promote cancer remains undefined. The rs6983267 SNP at 8q24 has been associated with many cancers, yet the SNP falls 335 kb from the nearest gene, c-MYC. We show that the beta-catenin-TCF4 transcription factor complex binds preferentially to the cancer risk-associated rs6983267(G) allele in colon cancer cells. We also show that the rs6983267 SNP has enhancer-related histone marks and can form a 335-kb chromatin loop to interact with the c-MYC promoter. Finally, we show that the SNP has no effect on the efficiency of chromatin looping to the c-MYC promoter but that the cancer risk-associated SNP enhances the expression of the linked c-MYC allele. Thus, cancer risk is a direct consequence of elevated c-MYC expression from increased distal enhancer activity and not from reorganization/creation of the large chromatin loop. The findings of these studies support a mechanism for intergenic SNPs that can promote cancer through the regulation of distal genes by utilizing preexisting large chromatin loops. PMID:20065031

  16. Chromosomal localization of the human gene encoding c-myc promoter-binding protein (MPB1) to chromosome 1p35-pter

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    White, R.A.; Dowler, L.L. [Univ. of Missouri, Kansas City, MO (United States); Adkison, L.R. [Mercer Univ. School of Medicine, Macon, GA (United States); Ray, R.B. [St. Louis Univ. Health Sciences Center, St. Louis, MO (United States)

    1997-02-01

    We report the mapping of the human gene MPB1 (c-myc promoter binding protein), a recently identified gene regulatory protein. MPB1 binds to the c-myc P2 promoter and exerts a negative regulatory role on c-myc transcription. Since exogenous expression from transfection of the MPB1 gene suppresses the tumorigenic property of breast cancer cells, there was interest in determining the chromosomal location of this gene. The human MPB1 gene was assigned to human chromosome 1p35-pter using Southern blot analyses of genomic DNAs from rodent-human somatic hybrid cell lines. A specific human genomic fragment was observed only in the somatic cell lines containing human chromosome 1 or the p35-pter region of the chromosome. 10 refs., 2 figs.

  17. Production of human c-myc protein in insect cells infected with a baculovirus expression vector.

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    Miyamoto, C.; Smith, G. E.; Farrell-Towt, J; Chizzonite, R.; Summers, M D; Ju, G.

    1985-01-01

    A cDNA fragment coding for human c-myc was inserted into the genome of the baculovirus Autographa californica nuclear polyhedrosis virus adjacent to the strong polyhedrin promoter. Insect cells infected with the recombinant virus produced significant amounts of c-myc protein, which constituted the major phosphoprotein component in these cells. By immunoprecipitation and immunoblot analysis, two proteins of 61 and 64 kilodaltons were detected with c-myc-specific antisera. The insect-derived pr...

  18. c-Myc Suppression of DNA Double-strand Break Repair

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    Zhaozhong Li

    2012-12-01

    Full Text Available c-Myc is a transcriptional factor that functions as a central regulator of cell growth, proliferation, and apoptosis. Overexpression of c-Myc also enhances DNA double-strand breaks (DSBs, genetic instability, and tumorigenesis. However, the mechanism(s involved remains elusive. Here, we discovered that γ-ray ionizing radiation-induced DSBs promote c-Myc to form foci and to co-localize with γ-H2AX. Conditional expression of c-Myc in HO15.19 c-Myc null cells using the Tet-Off/Tet-On inducible system results in down-regulation of Ku DNA binding and suppressed activities of DNA-dependent protein kinase catalytic subunit (DNA-PKcs and DNA end-joining, leading to inhibition of DSB repair and enhanced chromosomal and chromatid breaks. Expression of c-Myc reduces both signal and coding joins with decreased fidelity during V(DJ recombination. Mechanistically, c-Myc directly interacts with Ku70 protein through its Myc box II (MBII domain. Removal of the MBII domain from c-Myc abrogates its inhibitory effects on Ku DNA binding, DNA-PKcs, and DNA end-joining activities, which results in loss of c-Myc's ability to block DSB repair and V(DJ recombination. Interestingly, c-Myc directly disrupts the Ku/DNA-PKcs complex in vitro and in vivo. Thus, c-Myc suppression of DSB repair and V(DJ recombination may occur through inhibition of the nonhomologous end-joining pathway, which provides insight into the mechanism of c-Myc in the development of tumors through promotion of genomic instability.

  19. Brief inactivation of c-Myc is not sufficient for sustained regression of c-Myc-induced tumours of pancreatic islets and skin epidermis

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    Zervou Sevasti

    2004-12-01

    Full Text Available Abstract Background Tumour regression observed in many conditional mouse models following oncogene inactivation provides the impetus to develop, and a platform to preclinically evaluate, novel therapeutics to inactivate specific oncogenes. Inactivating single oncogenes, such as c-Myc, can reverse even advanced tumours. Intriguingly, transient c-Myc inactivation proved sufficient for sustained osteosarcoma regression; the resulting osteocyte differentiation potentially explaining loss of c-Myc's oncogenic properties. But would this apply to other tumours? Results We show that brief inactivation of c-Myc does not sustain tumour regression in two distinct tissue types; tumour cells in pancreatic islets and skin epidermis continue to avoid apoptosis after c-Myc reactivation, by virtue of Bcl-xL over-expression or a favourable microenvironment, respectively. Moreover, tumours progress despite reacquiring a differentiated phenotype and partial loss of vasculature during c-Myc inactivation. Interestingly, reactivating c-Myc in β-cell tumours appears to result not only in further growth of the tumour, but also re-expansion of the accompanying angiogenesis and more pronounced β-cell invasion (adenocarcinoma. Conclusions Given that transient c-Myc inactivation could under some circumstances produce sustained tumour regression, the possible application of this potentially less toxic strategy in treating other tumours has been suggested. We show that brief inactivation of c-Myc fails to sustain tumour regression in two distinct models of tumourigenesis: pancreatic islets and skin epidermis. These findings challenge the potential for cancer therapies aimed at transient oncogene inactivation, at least under those circumstances where tumour cell differentiation and alteration of epigenetic context fail to reinstate apoptosis. Together, these results suggest that treatment schedules will need to be informed by knowledge of the molecular basis and

  20. The Essential Cofactor TRRAP Recruits the Histone Acetyltransferase hGCN5 to c-Myc

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    McMahon, Steven B.; Wood, Marcelo A.; Cole, Michael D.

    2000-01-01

    The c-Myc protein functions as a transcription factor to facilitate oncogenic transformation; however, the biochemical and genetic pathways leading to transformation remain undefined. We demonstrate here that the recently described c-Myc cofactor TRRAP recruits histone acetylase activity, which is catalyzed by the human GCN5 protein. Since c-Myc function is inhibited by recruitment of histone deacetylase activity through Mad family proteins, these opposing biochemical activities are likely to be responsible for the antagonistic biological effects of c-Myc and Mad on target genes and ultimately on cellular transformation. PMID:10611234

  1. Detection of circulating antibodies against c-myc protein in cancer patient sera.

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    Ben-Mahrez, K.; Thierry, D.; Sorokine, I.; Danna-Muller, A.; Kohiyama, M

    1988-01-01

    We have partially purified an archaebacterial protein of 84 kD which shares common epitopes with the human c-myc protein as shown by its cross-reactivity with a commercialized anti-human c-myc antiserum. An antiserum raised against the 84 kD protein recognizes a 60 kD protein from HL-60 nuclei. This protein is also recognized by the anti-human c-myc antiserum. Using this archaebacterial protein as antigen for Western blot analysis, we found that the human c-myc oncogene product could be immun...

  2. Elevated c-myc protooncogene expression in autosomal recessive polycystic kidney disease

    International Nuclear Information System (INIS)

    The polycystic kidney diseases (PKDs) are a group of disorders characterized by the growth of epithelial cysts from the nephrons and collecting ducts of kidney tubules. The diseases can be inherited or can be provoked by environmental factors. To investigate the molecular basis of the abnormal cell growth associated with PKD, c-myc protooncogene expression was studied in a mouse model for autosomal recessive PKD. Homozygous recessive C57BL/6J (cpk/cpk) mice develop massively enlarged cystic kidneys and die from renal failure shortly after 3 weeks of age. Quantitative dot blot and RNA blot hybridization experiments in which whole kidney poly(A)+ RNA was hybridized with a c-myc RNA probe showed a 2- to 6-fold increase in c-myc mRNA at 2 weeks, and a 25- to 30-fold increase in c-myc mRNA at 3 weeks of age in polycystic mice, as compared to normal littermates. c-myc expression was also examined under two conditions in which kidney cell growth was experimentally induced in normal adult mice: compensatory renal hypertrophy and tubule regeneration following folic acid-induced renal cell injury. While compensatory hypertrophy resulted in only a small increase in c-myc, folic acid treatment gave rise after 24 hr to a 12-fold increase in c-myc RNA. The induction of c-myc by folic acid is consistent with increased cellular proliferation regenerating tubules. In contrast, polycystic kidneys show only a minimal increase in cellular proliferation over that seen in normal kidneys, while c-myc levels were found to be markedly elevated. Thus, the level of c-myc expression in cystic kidneys appears to be out of proportion to the rate of cell division, suggesting that elevated and potentially abnormal c-myc expression may be involved in the pathogenesis of PKD

  3. Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1 p30{sup II} accessory protein and the induction of oncogenic cellular transformation by p30{sup II}/c-MYC

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    Romeo, Megan M.; Ko, Bookyung; Kim, Janice; Brady, Rebecca; Heatley, Hayley C.; He, Jeffrey; Harrod, Carolyn K.; Barnett, Braden [Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376 (United States); Ratner, Lee [Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Lairmore, Michael D. [University of California-Davis, School of Veterinary Medicine, One Shields Avenue, Davis, CA 95618 (United States); Martinez, Ernest [Department of Biochemistry, University of California, Riverside, CA 92521 (United States); Lüscher, Bernhard [Institute of Biochemistry, Klinikum, RWTH Aachen University, Pauwelsstrasse 30, 52057 Aachen (Germany); Robson, Craig N. [Northern Institute for Cancer Research, Newcastle University, The Medical School, Newcastle upon Tyne, NE2 4HH (United Kingdom); Henriksson, Marie [Department of Microbiology, Cell and Tumor Biology, Karolinska Institutet, Stockholm (Sweden); Harrod, Robert, E-mail: rharrod@smu.edu [Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376 (United States)

    2015-02-15

    The human T-cell leukemia retrovirus type-1 (HTLV-1) p30{sup II} protein is a multifunctional latency-maintenance factor that negatively regulates viral gene expression and deregulates host signaling pathways involved in aberrant T-cell growth and proliferation. We have previously demonstrated that p30{sup II} interacts with the c-MYC oncoprotein and enhances c-MYC-dependent transcriptional and oncogenic functions. However, the molecular and biochemical events that mediate the cooperation between p30{sup II} and c-MYC remain to be completely understood. Herein we demonstrate that p30{sup II} induces lysine-acetylation of the c-MYC oncoprotein. Acetylation-defective c-MYC Lys→Arg substitution mutants are impaired for oncogenic transformation with p30{sup II} in c-myc{sup −/−} HO15.19 fibroblasts. Using dual-chromatin-immunoprecipitations (dual-ChIPs), we further demonstrate that p30{sup II} is present in c-MYC-containing nucleoprotein complexes in HTLV-1-transformed HuT-102 T-lymphocytes. Moreover, p30{sup II} inhibits apoptosis in proliferating cells expressing c-MYC under conditions of genotoxic stress. These findings suggest that c-MYC-acetylation is required for the cooperation between p30{sup II}/c-MYC which could promote proviral replication and contribute to HTLV-1-induced carcinogenesis. - Highlights: • Acetylation of c-MYC is required for oncogenic transformation by HTLV-1 p30{sup II}/c-MYC. • Acetylation-defective c-MYC mutants are impaired for foci-formation by p30{sup II}/c-MYC. • The HTLV-1 p30{sup II} protein induces lysine-acetylation of c-MYC. • p30{sup II} is present in c-MYC nucleoprotein complexes in HTLV-1-transformed T-cells. • HTLV-1 p30{sup II} inhibits apoptosis in c-MYC-expressing proliferating cells.

  4. Effect of C-myc Antisense Oligodeoxynucleotides on Hypoxia-induced Proliferation of Pulmonary Vascular Pericytes

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the effect of c-myc antisense oligodeoxynucleotides (ODNs) on proliferation of pulmonary vascular pericytes (PC) induced by hypoxia, cell culture, dot hybridization using probe of digoxigenin-11-dUTP-labeled cDNA,3H-thymidine incorporation, immunocytochemical technique and image analysis methods were used to observe the effect of c-myc antisense ODNs on expression of c-myc gene and proliferating cell nuclear antigen (PCNA), and 3H-thymidine incorporation of PC induced by hypoxia. The results showed that hypoxia could significantly enhance the expression of c-myc and PCNA (P<0.01), and elevate 3H-thymidine incorporation of PC (P<0.01), but antisense ODNs could significantly inhibit the expression of c-myc and PCNA (P<0.05), and 3H-thymidine incorporation of PC (P<0.01). It was suggested that hypoxia could promote the proliferation of PC by up-regulating the expression of c-myc gene, but c-myc antisense ODNs could inhibit hypoxia-induced proliferation of PC by downregulating the expression of c-myc gene.

  5. Deregulation of c-myc and SV40Tag causing brain tumor in mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Deregulated expressions of both c-myc and simian virus 40 large T antigen (SV40Tag) are consistent features of lots of tumors. To investigate whether the expression of c-myc and SV40Tag in mouse might help develop a model of human tumor, we generated c-myc transgenics by inserting human c-myc gene into pTRE2 of Tet-On system. We obtained conditional expression of SV40Tag transgenics by the Tet-On system from Yangzhou University. Crossing the c-myc transgenic mouse with the SV40Tag transgenic mice to generate bitransgenics we got double-transgenic mice expressing c-myc and SV40Tag by the Tet-On system. After being treated with doxycycline continuously, single-transgenic SV40Tag mice developed brain tumor infrequently (3 of 84, 3.6%) with a long onset (185 d on average). In contrast, double-transgenic c-myc/SV40Tag mice developed brain tumor with a short onset (96 days on average) and a 41% brain tumor incidence rate (7 of 17, 41%). This tumor was assumed to be medulloblastoma. Our experiments suggest that deregulated expression of c-myc and SV40Tag in brain might generate a mouse model of human brain tumor that recapitulates some features of human medulloblastoma.

  6. Glutathione Depletion Induced by c-Myc Downregulation Triggers Apoptosis on Treatment with Alkylating Agents

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    Annamaria Biroccio

    2004-05-01

    Full Text Available Here we investigate the mechanism(s involved in the c-Myc-dependent drug response of melanoma cells. By using three M14-derived c-Myc low-expressing clones, we demonstrate that alkylating agents, cisplatin and melphalan, trigger apoptosis in the c-Myc antisense transfectants, but not in the parental line. On the contrary, topoisomerase inhibitors, adriamycin and camptothecin, induce apoptosis to the same extent regardless of c-Myc expression. Because we previously demonstrated that c-Myc downregulation decreases glutathione (GSH content, we evaluated the role of GSH in the apoptosis induced by the different drugs. In control cells treated with one of the alkylating agents or the others, GSH depletion achieved by L-buthionine-sulfoximine preincubation opens the apoptotic pathway. The apoptosis proceeded through early Bax relocalization, cytochrome c release, concomitant caspase-9 activation, whereas reactive oxygen species production and alteration of mitochondria membrane potential were late events. That GSH was determining in the c-Myc-dependent druginduced apoptosis was demonstrated by altering the intracellular GSH content of the c-Myc low-expressing cells up to the level of controls. Indeed, GSH ethyl ester-mediated increase of GSH abrogated apoptosis induced by cisplatin and melphalan by inhibition of Baxicytochrome c redistribution. The relationship among c-Myc, GSH content, the response to alkylating agent has been also evaluated in the M14 Myc overexpressing clones as well as in the melanoma JR8 c-Myc antisense transfectants. All together, these results demonstrate that GSH plays a key role in governing c-Myc-dependent drug-induced apoptosis.

  7. Sulforaphane Inhibits c-Myc-Mediated Prostate Cancer Stem-Like Traits.

    Science.gov (United States)

    Vyas, Avani R; Moura, Michelle B; Hahm, Eun-Ryeong; Singh, Krishna Beer; Singh, Shivendra V

    2016-11-01

    Preventive and therapeutic efficiencies of dietary sulforaphane (SFN) against human prostate cancer have been demonstrated in vivo, but the underlying mechanism(s) by which this occurs is poorly understood. Here, we show that the prostate cancer stem cell (pCSC)-like traits, such as accelerated activity of aldehyde dehydrogenase 1 (ALDH1), enrichment of CD49f+ fraction, and sphere forming efficiency, are attenuated by SFN treatment. Interestingly, the expression of c-Myc, an oncogenic transcription factor that is frequently deregulated in prostate cancer cells, was markedly suppressed by SFN both in vitro and in vivo. This is biologically relevant, because the lessening of pCSC-like phenotypes mediated by SFN was attenuated when c-Myc was overexpressed. Naturally occurring thio, sulfinyl, and sulfonyl analogs of SFN were also effective in causing suppression of c-Myc protein level. However, basal glycolysis, a basic metabolic pathway that can also be promoted by c-Myc overexpression, was not largely suppressed by SFN, implying that, in addition to c-Myc, there might be another SFN-sensitive cellular factor, which is not directly involved in basal glycolysis, but cooperates with c-Myc to sustain pCSC-like phenotypes. Our study suggests that oncogenic c-Myc is a target of SFN to prevent and eliminate the onset of human prostate cancer. J. Cell. Biochem. 117: 2482-2495, 2016. © 2016 Wiley Periodicals, Inc.

  8. TELOMERASE ACTIVITY IN COLORECTAL CARCINOMA AND ITS CORRELATION WITH EXPRESSION OF C-MYC

    Institute of Scientific and Technical Information of China (English)

    LIU Jian-Lun; GE Lian-ying; ZHANG Gui-nian

    2005-01-01

    Objective: To study the role of telomerase activity and c-myc in pathogenesis and progression of colorectal carcinoma,and to investigate the possible regulatory mechanism of telomerase activation. Methods: A modified telomeric repeat amplification protocol (TRAP) and immunohistochemical staining was used to detect telomerase activity and the expression of c-myc in tissue samples from colorectal carcinoma, paracarcinomatousl tissues, normal mucosa, and adenomatoid polyp.Results: The positive rates of telomerase activity and c-myc expression were 83.33% and 80.00% in colorectal carcinoma,13.33% and 23.33% in paracarcinomatousl tissues, 13.33% and 20.00% in normal mucosa, and 10.00% and 45.00% in adenomatoid polyp respectively, they were significantly higher in colorectal carcinoma than in paracarcinomatousl tissues,normal mucosa, and adenomatoid polyp (P<0.05). The rates of telomerase activity and c-myc expression were much higher in colorectal carcinoma with lymph nodes metastases than that without lymph nodes metastases. The expression of c-myc was found being significantly higher in the telomerase positive colorectal carcinoma than in the telomerase negative group(P<0.05). Conclusion: The activation of telomerase and abnormal expression of c-myc might play an important role in the process of carcinogenesis and progression of colorectal carcinoma. The over-expression of c-myc may be related to telomerase activation and up-regulation in colorectal carcinoma.

  9. c-Myc is essential to prevent endothelial pro-inflammatory senescent phenotype.

    Directory of Open Access Journals (Sweden)

    Victoria Florea

    Full Text Available The proto-oncogene c-Myc is vital for vascular development and promotes tumor angiogenesis, but the mechanisms by which it controls blood vessel growth remain unclear. In the present work we investigated the effects of c-Myc knockdown in endothelial cell functions essential for angiogenesis to define its role in the vasculature. We provide the first evidence that reduction in c-Myc expression in endothelial cells leads to a pro-inflammatory senescent phenotype, features typically observed during vascular aging and pathologies associated with endothelial dysfunction. c-Myc knockdown in human umbilical vein endothelial cells using lentivirus expressing specific anti-c-Myc shRNA reduced proliferation and tube formation. These functional defects were associated with morphological changes, increase in senescence-associated-β-galactosidase activity, upregulation of cell cycle inhibitors and accumulation of c-Myc-deficient cells in G1-phase, indicating that c-Myc knockdown in endothelial cells induces senescence. Gene expression analysis of c-Myc-deficient endothelial cells showed that senescent phenotype was accompanied by significant upregulation of growth factors, adhesion molecules, extracellular-matrix components and remodeling proteins, and a cluster of pro-inflammatory mediators, which include Angptl4, Cxcl12, Mdk, Tgfb2 and Tnfsf15. At the peak of expression of these cytokines, transcription factors known to be involved in growth control (E2f1, Id1 and Myb were downregulated, while those involved in inflammatory responses (RelB, Stat1, Stat2 and Stat4 were upregulated. Our results demonstrate a novel role for c-Myc in the prevention of vascular pro-inflammatory phenotype, supporting an important physiological function as a central regulator of inflammation and endothelial dysfunction.

  10. Nuclear localization of phosphorylated c-Myc protein in human tumor cells.

    Directory of Open Access Journals (Sweden)

    C. Soldani

    2010-05-01

    Full Text Available Using immunocytochemical techniques at light and electron microscopy, we analysed the distribution of phosphorylated c-Myc in actively proliferating human HeLa cells. The distribution pattern of c-Myc was also compared with those of other ribonucleoprotein (RNP-containing components (PANA, hnRNP-core proteins, fibrillarin or RNP-associated nuclear proteins (SC-35 splicing factor. Our results provide the first evidence that phosphorylated c-Myc accumulates in the nucleus of tumor cells, where it colocalizes with fibrillarin, both in the nucleolus and in extranucleolar structures.

  11. Multiple mechanisms regulate c-myc gene expression during normal T cell activation.

    OpenAIRE

    Lindsten, T; June, C H; Thompson, C. B.

    1988-01-01

    Quiescent normal human T cells express low levels of steady-state c-myc mRNA as a result of low constitutive promoter utilization, a block to transcriptional elongation within the gene, and rapid degradation of c-myc mRNA in the cytoplasm. Following the activation of the T cell receptor (TCR)/CD3 complex, quiescent T cells are induced to express c-myc mRNA. Two intracellular pathways, one involving protein kinase C activation and the other mediated by increased intracellular calcium concentra...

  12. AP-2α Inhibits c-MYC Induced Oxidative Stress and Apoptosis in HaCaT Human Keratinocytes

    Directory of Open Access Journals (Sweden)

    Lei Yu

    2009-01-01

    AP-2 may have a direct effect on the c-myc gene. Chromatin immunoprecipitation assays demonstrated that AP-2 proteins bound to a cluster of AP-2 binding sites located within a 2 kb upstream regulatory region of c-myc These results suggest that the negative regulation of AP-2 on c-MYC activity was achieved through binding of AP-2 protein to the c-myc gene. The effects of AP-2 on c-MYC induced ROS accumulation and apoptosis in epidermal keratinocytes are likely to play an important role in cell growth, differentiation and carcinogenesis of the skin.

  13. Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo

    OpenAIRE

    Phesse, T J; Myant, K.B.; Cole, A M; Ridgway, R.A.; Pearson, H; Muncan, V.; van den Brink, G R; Vousden, K H; Sears, R.; Vassilev, L T; Clarke, A R; Sansom, O J

    2014-01-01

    Recent studies have suggested that C-MYC may be an excellent therapeutic cancer target and a number of new agents targeting C-MYC are in preclinical development. Given most therapeutic regimes would combine C-MYC inhibition with genotoxic damage, it is important to assess the importance of C-MYC function for DNA damage signalling in vivo. In this study, we have conditionally deleted the c-Myc gene in the adult murine intestine and investigated the apoptotic response of intestinal enterocytes ...

  14. Therapeutic aspects of c-MYC signaling in inflammatory and cancerous colonic diseases.

    Science.gov (United States)

    Sipos, Ferenc; Firneisz, Gábor; Műzes, Györgyi

    2016-09-21

    Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Both sporadical and colitis-associated colorectal carcinogenesis are multi-step, complex processes arising from the uncontrolled proliferation and spreading of malignantly transformed cell clones with the obvious ability to evade the host's protective immunity. In cells upon DNA damage several proto-oncogenes, including c-MYC are activated in parelell with the inactivation of tumor suppressor genes. The target genes of the c-MYC protein participate in different cellular functions, including cell cycle, survival, protein synthesis, cell adhesion, and micro-RNA expression. The transcriptional program regulated by c-MYC is context dependent, therefore the final cellular response to elevated c-MYC levels may range from increased proliferation to augmented apoptosis. Considering physiological intestinal homeostasis, c-MYC displays a fundamental role in the regulation of cell proliferation and crypt cell number. However, c-MYC gene is frequently deregulated in inflammation, and overexpressed in both sporadic and colitis-associated colon adenocarcinomas. Recent results demonstrated that endogenous c-MYC is essential for efficient induction of p53-dependent apoptosis following DNA damage, but c-MYC function is also involved in and regulated by autophagy-related mechanisms, while its expression is affected by DNA-methylation, or histone acetylation. Molecules directly targeting c-MYC, or agents acting on other genes involved in the c-MYC pathway could be

  15. Therapeutic aspects of c-MYC signaling in inflammatory and cancerous colonic diseases.

    Science.gov (United States)

    Sipos, Ferenc; Firneisz, Gábor; Műzes, Györgyi

    2016-09-21

    Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Both sporadical and colitis-associated colorectal carcinogenesis are multi-step, complex processes arising from the uncontrolled proliferation and spreading of malignantly transformed cell clones with the obvious ability to evade the host's protective immunity. In cells upon DNA damage several proto-oncogenes, including c-MYC are activated in parelell with the inactivation of tumor suppressor genes. The target genes of the c-MYC protein participate in different cellular functions, including cell cycle, survival, protein synthesis, cell adhesion, and micro-RNA expression. The transcriptional program regulated by c-MYC is context dependent, therefore the final cellular response to elevated c-MYC levels may range from increased proliferation to augmented apoptosis. Considering physiological intestinal homeostasis, c-MYC displays a fundamental role in the regulation of cell proliferation and crypt cell number. However, c-MYC gene is frequently deregulated in inflammation, and overexpressed in both sporadic and colitis-associated colon adenocarcinomas. Recent results demonstrated that endogenous c-MYC is essential for efficient induction of p53-dependent apoptosis following DNA damage, but c-MYC function is also involved in and regulated by autophagy-related mechanisms, while its expression is affected by DNA-methylation, or histone acetylation. Molecules directly targeting c-MYC, or agents acting on other genes involved in the c-MYC pathway could be

  16. Therapeutic aspects of c-MYC signaling in inflammatory and cancerous colonic diseases

    Science.gov (United States)

    Sipos, Ferenc; Firneisz, Gábor; Műzes, Györgyi

    2016-01-01

    Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Both sporadical and colitis-associated colorectal carcinogenesis are multi-step, complex processes arising from the uncontrolled proliferation and spreading of malignantly transformed cell clones with the obvious ability to evade the host’s protective immunity. In cells upon DNA damage several proto-oncogenes, including c-MYC are activated in parelell with the inactivation of tumor suppressor genes. The target genes of the c-MYC protein participate in different cellular functions, including cell cycle, survival, protein synthesis, cell adhesion, and micro-RNA expression. The transcriptional program regulated by c-MYC is context dependent, therefore the final cellular response to elevated c-MYC levels may range from increased proliferation to augmented apoptosis. Considering physiological intestinal homeostasis, c-MYC displays a fundamental role in the regulation of cell proliferation and crypt cell number. However, c-MYC gene is frequently deregulated in inflammation, and overexpressed in both sporadic and colitis-associated colon adenocarcinomas. Recent results demonstrated that endogenous c-MYC is essential for efficient induction of p53-dependent apoptosis following DNA damage, but c-MYC function is also involved in and regulated by autophagy-related mechanisms, while its expression is affected by DNA-methylation, or histone acetylation. Molecules directly targeting c-MYC, or agents acting on other genes involved in the c-MYC pathway could be

  17. Overexpression of c-myc induces epithelial mesenchymal transition in mammary epithelial cells.

    Science.gov (United States)

    Cho, Kyoung Bin; Cho, Min Kyong; Lee, Won Young; Kang, Keon Wook

    2010-07-28

    The c-myc gene is frequently overexpressed in human breast cancer and its target genes are involved in tumorigenesis. Epithelial mesenchymal transitions (EMT), where cells undergo a developmental switch from a polarized epithelial phenotype to a highly motile mesenchymal phenotype, are associated with invasion and motility of cancer cells. Basal E-cadherin expression was down-regulated in c-myc overexpressing MCF10A (c-myc-MCF10A) cells compared to GFP-overexpressing MCF10A (GFP-MCF10A) cells, while N-cadherin was distinctly increased in c-myc-MCF10A cells. Given that glycogen synthase kinase-3beta (GSK-3beta) and the snail axis have key roles in E-cadherin deregulation during EMT, we investigated the role of GSK-3beta/snail signaling pathways in the induction of EMT by c-myc overexpression. In contrast to GFP-MCF10A cells, both the transcriptional activity and the ubiquitination-dependent protein stability of snail were enhanced in c-myc-MCF10A cells, and this was reversed by GSK-3beta overexpression. We also found that c-myc overexpression inhibits GSK-3beta activity through activation of extracellular signal-regulated kinase (ERK). Inhibition of ERK by dominant negative mutant transfection or chemical inhibitor significantly suppressed snail gene transcription. These results suggest that c-myc overexpression during transformation of mammary epithelial cells (MEC) is involved in EMTs via ERK-dependent GSK-3beta inactivation and subsequent snail activation.

  18. Lack of Cyclin-Dependent Kinase 4 Inhibits c-myc Tumorigenic Activities in Epithelial Tissues

    OpenAIRE

    Miliani de Marval, Paula L.; Macias, Everardo; Rounbehler, Robert; Sicinski, Piotr; Kiyokawa, Hiroaki; David G. Johnson; Conti, Claudio J.; Rodriguez-Puebla, Marcelo L

    2004-01-01

    The proto-oncogene c-myc encodes a transcription factor that is implicated in the regulation of cellular proliferation, differentiation, and apoptosis and that has also been found to be deregulated in several forms of human and experimental tumors. We have shown that forced expression of c-myc in epithelial tissues of transgenic mice (K5-Myc) resulted in keratinocyte hyperproliferation and the development of spontaneous tumors in the skin and oral cavity. Although a number of genes involved i...

  19. Transcript Regulation of Human Telomerase Reverse Transcriptase by c-myc and mad1

    Institute of Scientific and Technical Information of China (English)

    Lin ZOU; Peng-Hui ZHANG; Chun-Li LUO; Zhi-Guang TU

    2005-01-01

    Telomerase activity is highly positive correlated to most malignant neoplasms. Human telomerase reverse transcriptase (hTERT) is the rate-limiting factor of telomerase activity. Recent studies have shown that the expression of hTERT is mainly determined by its transcript regulation. Among the transcript regulation factors of hTERT, c-myc and mad1 are well known. Here, we constructed c-myc and mad1 eukaryotic expression vectors, then co-transfected them with the wild-type (Tw) or mutant hTERT promoter (Td)luciferase reporter plasmid, which were double-mutated in the E-box sequences from CACGTG to CACCTG of Tw. The change of luciferase activity in different cells was detected. The results showed that Tw was obviously activated in T24 and EJ bladder cancer cells, but not in normal fibrocytes. c-myc and mad1 had positive and negative effects respectively on the Tw transcript in a dose-dependent manner, while the roles of c-myc and mad1 in regulating the Td transcript were reversed. c-myc combined with mad1 can downregulate Tw but not Td. These observations indicate that c-myc and mad1 can regulate the hTERT transcript in a different manner in hTERT positive cells, but not in normal cells. This may provide an insight into some telomerase-related carcinogenesis mechanisms.

  20. Regulation of human ornithine decarboxylase expression by the c-Myc.Max protein complex.

    Science.gov (United States)

    Peña, A; Reddy, C D; Wu, S; Hickok, N J; Reddy, E P; Yumet, G; Soprano, D R; Soprano, K J

    1993-12-25

    The presence of a CACGTG element within a region of the human ornithine decarboxylase (ODC) promoter located at -491 to -474 base pairs 5' to the start site of transcription suggested that the c-Myc.Max protein complex may play a role in the regulation of ODC expression during growth. Electrophoretic mobility shift assays and methylation interference analysis showed that the nuclei of WI-38 cells expressing ODC contained proteins that bound to this region of the ODC gene in a manner that correlated with growth-associated ODC expression. Also, use of antibodies against c-Myc and Max and purified recombinant c-Myc and Max protein in the electrophoretic mobility shift assay confirmed that these proteins can specifically bind this portion of the human ODC promoter. Transient transfection studies showed that increase in the level of c-Myc and/or Max led to a significant enhancement of expression of a human ODC promoter-CAT reporter construct. Moreover, treatment of actively growing WI-38 cells with an antisense oligomer to c-Myc reduced the amount of endogenous protein complex formed and the amount of endogenous ODC mRNA expressed. These studies show that the c-Myc.Max protein complex plays a role in the transcriptional regulation of human ODC in vivo.

  1. Differential regulation of the c-Myc/Lin28 axis discriminates subclasses of rearranged MLL leukemia

    Science.gov (United States)

    Chen, Lili; Sun, Yuqing; Wang, Jingya; Jiang, Hui; Muntean, Andrew G.

    2016-01-01

    MLL rearrangements occur in myeloid and lymphoid leukemias and are generally associated with a poor prognosis, however this varies depending on the fusion partner. We modeled acute myeloid leukemia (AML) in mice using various MLL fusion proteins (MLL-FPs) and observed significantly different survival outcomes. To better understand the differences between these leukemias, we examined the genome wide expression profiles of leukemic cells transformed with different MLL-FPs. RNA-sequencing and pathway analysis identified the c-Myc transcriptional program as one of the top distinguishing features. c-Myc protein levels were highly correlative with AML disease latency in mice. Functionally, overexpression of c-Myc resulted in a more aggressive proliferation rate in MLL-FP cell lines. While all MLL-FP transformed cells displayed sensitivity to BET inhibitors, high c-Myc expressing cells showed greater resistance to Brd4 inhibition. The Myc target Lin28B was also differentially expressed in MLL-FP cell lines in agreement with c-Myc expression. Examination of Lin28B miRNAs targets revealed that let-7g was significantly increased in leukemic cells associated with the longest disease latency and forced let-7g expression induced differentiation of leukemic blasts. Thus, differential regulation of the c-Myc/Lin28/let-7g program by different MLL-FPs is functionally related to disease latency and BET inhibitor resistance in MLL leukemias. PMID:27007052

  2. Evidence that a triplex-forming oligodeoxyribonucleotide binds to the c-myc promoter in HeLa cells, thereby reducing c-myc mRNA levels

    Energy Technology Data Exchange (ETDEWEB)

    Postel, E.H.; Flint, S.J. (Princeton Univ., NJ (United States)); Kessler, D.J.; Hogan, M.E. (Baylor College of Medicine, The Woodlands, TX (United States))

    1991-09-15

    A synthetic 27-base-long oligodeoxyribonucleotide, termed PU1, has been shown to bind to duplex DNA to form a triplex at a single site within the human c-myc P1 promoter. PU1 has been administered to HeLa cells in culture to examine the feasibility of influencing transcription of the c-myc gene in vivo. It is shown that uptake of PU1 into the nucleus of HeLa cells is efficient and that the compound remains intact for at least 4 hours. In nuclei extracted from PU1-treated cells, inhibition of DNase I cleavage is detected within the c-myc P1 promoter at the target site for triplex formation. The inhibition is shown to be both site and oligodeoxyribonucleotide specific. After cellular uptake of PU1, it is shown that steady-state mRNA arising from the c-myc P2 initiation site, and relative to mRNA derived form the {beta}-actin promoter. Significant mRNA repression is not seen upon treating cells with oligodeoxyuribonucleotides that fail to bind to the P1 promoter target. Taken together, these data suggest that triplex formation can occur between an exogenous oligodeoxy-ribonucleotide and duplex DNA in the nucleus of treated cells.

  3. Discovery of a Family of Genomic Sequences Which Interact Specifically with the c-MYC Promoter to Regulate c-MYC Expression

    Science.gov (United States)

    Thomas, Shelia D.; Rouchka, Eric C.; Miller, Donald M.

    2016-01-01

    G-quadruplex forming sequences are particularly enriched in the promoter regions of eukaryotic genes, especially of oncogenes. One of the most well studied G-quadruplex forming sequences is located in the nuclease hypersensitive element (NHE) III1 of the c-MYC promoter region. The oncoprotein c-MYC regulates a large array of genes which play important roles in growth regulation and metabolism. It is dysregulated in >70% of human cancers. The silencer NHEIII1 located upstream of the P1 promoter regulates up-to 80% of c-MYC transcription and includes a G-quadruplex structure (Pu27) that is required for promoter inhibition. We have identified, for the first time, a family of seventeen G-quadruplex-forming motifs with >90% identity with Pu27, located on different chromosomes throughout the human genome, some found near or within genes involved in stem cell maintenance or neural cell development. Notably, all members of the Pu27 family interact specifically with NHEIII1 sequence, in vitro. Crosslinking studies demonstrate that Pu27 oligonucleotide binds specifically to the C-rich strand of the NHEIII1 resulting in the G-quadruplex structure stabilization. Pu27 homologous sequences (Pu27-HS) significantly inhibit leukemic cell lines proliferation in culture. Exposure of U937 cells to the Pu27-HS induces cell growth inhibition associated with cell cycle arrest that is most likely due to downregulation of c-MYC expression at the RNA and/or protein levels. Expression of SOX2, another gene containing a Pu27-HS, was affected by Pu27-HS treatment as well. Our data suggest that the oligonucleotides encoding the Pu27 family target complementary DNA sequences in the genome, including those of the c-MYC and SOX2 promoters. This effect is most likely cell type and cell growth condition dependent. The presence of genomic G-quadruplex-forming sequences homologous to Pu27 of c-MYC silencer and the fact that they interact specifically with the parent sequence suggest a common

  4. VARIATION AND SIGNIFICANCE OF C-MYC PROTEIN IN RAT CARDIAC VOLUME-OVERLOAD HYP ERTROPHY

    Institute of Scientific and Technical Information of China (English)

    刘华胜; 马爱群; 王一理; 刘勇; 李恒力; 田红燕

    2002-01-01

    Objective To investigate the change of c-myc protein, which was chosen as the response indicator to volume-overload. Methods The time and spatial course of c-myc protein expressi on on the model of rat cardiac volume-overload hyper trophy was examined by immunohistochemical study. Results The immunohistochemica l study indicated the expression of c-myc protein was increased obviously at 4 -6 hours (62.73%) than that of control (45.41%, P<0.01) after the volume-o verload, then decreased gradually along with development of volume-overload hyp ertrophy and was decreased extremely at 5 months(r=-0.514,P<0.01).Conclusion There are disorders in the signal transduction pathways governing the hypertrophic respon se of cardiomyocytes in hypertrophic myocardium. C-myc gene and the product of it may be only the promoter gene of myocardial hypertrophy. Once switching on, c-myc gene and the product of it do not act anymore;While it may be that c-my c gene and the product of it increased following with myocardial hypertrophy, an d have not direct relation to the occurrence and development of myocardial hyper trophy.

  5. Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo.

    Science.gov (United States)

    Phesse, T J; Myant, K B; Cole, A M; Ridgway, R A; Pearson, H; Muncan, V; van den Brink, G R; Vousden, K H; Sears, R; Vassilev, L T; Clarke, A R; Sansom, O J

    2014-06-01

    Recent studies have suggested that C-MYC may be an excellent therapeutic cancer target and a number of new agents targeting C-MYC are in preclinical development. Given most therapeutic regimes would combine C-MYC inhibition with genotoxic damage, it is important to assess the importance of C-MYC function for DNA damage signalling in vivo. In this study, we have conditionally deleted the c-Myc gene in the adult murine intestine and investigated the apoptotic response of intestinal enterocytes to DNA damage. Remarkably, c-Myc deletion completely abrogated the immediate wave of apoptosis following both ionizing irradiation and cisplatin treatment, recapitulating the phenotype of p53 deficiency in the intestine. Consistent with this, c-Myc-deficient intestinal enterocytes did not upregulate p53. Mechanistically, this was linked to an upregulation of the E3 Ubiquitin ligase Mdm2, which targets p53 for degradation in c-Myc-deficient intestinal enterocytes. Further, low level overexpression of c-Myc, which does not impact on basal levels of apoptosis, elicited sustained apoptosis in response to DNA damage, suggesting c-Myc activity acts as a crucial cell survival rheostat following DNA damage. We also identify the importance of MYC during DNA damage-induced apoptosis in several other tissues, including the thymus and spleen, using systemic deletion of c-Myc throughout the adult mouse. Together, we have elucidated for the first time in vivo an essential role for endogenous c-Myc in signalling DNA damage-induced apoptosis through the control of the p53 tumour suppressor protein. PMID:24583641

  6. HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc.

    Science.gov (United States)

    Li, Yinghui; Wang, Zhen; Shi, Hui; Li, Hang; Li, Leilei; Fang, Runping; Cai, Xiaoli; Liu, Bowen; Zhang, Xiaodong; Ye, Lihong

    2016-01-15

    c-Myc is regarded as a transcription factor, but the basis for its function remains unclear. Here, we define a long noncoding RNA (lncRNA)/protein complex that mediates the transcriptional activation by c-Myc in breast cancer cells. Among 388 c-Myc target genes in human MCF-7 breast cancer cells, we found that their promoters could be occupied by the oncoprotein HBXIP. We confirmed that the HBXIP expression correlated with expression of the c-Myc target genes cyclin A, eIF4E, and LDHA. RNAi-mediated silencing of HBXIP abolished c-Myc-mediated upregulation of these target genes. Mechanistically, HBXIP interacted directly with c-Myc through the leucine zippers and recruited the lncRNA Hotair along with the histone demethylase LSD1, for which Hotair serves as a scaffold. Silencing of HBXIP, Hotair, or LSD1 was sufficient to block c-Myc-enhanced cancer cell growth in vitro and in vivo. Taken together, our results support a model in which the HBXIP/Hotair/LSD1 complex serves as a critical effector of c-Myc in activating transcription of its target genes, illuminating long-standing questions on how c-Myc drives carcinogenesis.

  7. Interrelationship between chromosome 8 aneuploidy, C-MYC amplification and increased expression in individuals from northern Brazil with gastric adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Danielle Queiroz Calcagno; Márcia Valéria Pitombeira Ferreira; Marília de Arruda Cardoso Smith; Rommel Rodríguez Burbano; Mariana Ferreira Leal; Aline Damaceno Seabra; André Salim Khayat; Elizabeth Suchi Chen; Samia Demachki; Paulo Pimentel Assump(c)(a)o; Mario Henrique Gir(a)o Faria; Silvia Helena Barem Rabenhorst

    2006-01-01

    AIM: To investigate chromosome 8 numerical aberrations, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histopathological characteristics of gastric tumors.METHODS: Specimens were collected surgically from seven patients with gastric adenocarcinomas. Immunostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH) for C-MYC gene and chromosome 8centromere were performed.RESULTS: All the cases showed chromosome 8 aneuploidy and C-MYC amplification, in both the diffuse and intestinal histopathological types of Lauren. No significant difference (P < 0.05) was observed between the level of chromosome 8 ploidy and the site, stage or histological type of the adenocarcinomas. C-MYC high amplification,like homogeneously stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type.Structural rearrangement of C-MYC, like translocation,was observed only in the diffuse type. Regarding C-MYC gene, a significant difference (P < 0.05) was observed between the two histological types. The C-MYC protein was expressed in all the studied cases. In the intestinaltype the C-MYC immunoreactivity was localized only in the nucleus and in the diffuse type in the nucleus and cytoplasm.CONCLUSION: Distinct patterns of alterations between intestinal and diffuse types of gastric tumors support the hypothesis that these types follow different genetic pathways.

  8. HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc.

    Science.gov (United States)

    Li, Yinghui; Wang, Zhen; Shi, Hui; Li, Hang; Li, Leilei; Fang, Runping; Cai, Xiaoli; Liu, Bowen; Zhang, Xiaodong; Ye, Lihong

    2016-01-15

    c-Myc is regarded as a transcription factor, but the basis for its function remains unclear. Here, we define a long noncoding RNA (lncRNA)/protein complex that mediates the transcriptional activation by c-Myc in breast cancer cells. Among 388 c-Myc target genes in human MCF-7 breast cancer cells, we found that their promoters could be occupied by the oncoprotein HBXIP. We confirmed that the HBXIP expression correlated with expression of the c-Myc target genes cyclin A, eIF4E, and LDHA. RNAi-mediated silencing of HBXIP abolished c-Myc-mediated upregulation of these target genes. Mechanistically, HBXIP interacted directly with c-Myc through the leucine zippers and recruited the lncRNA Hotair along with the histone demethylase LSD1, for which Hotair serves as a scaffold. Silencing of HBXIP, Hotair, or LSD1 was sufficient to block c-Myc-enhanced cancer cell growth in vitro and in vivo. Taken together, our results support a model in which the HBXIP/Hotair/LSD1 complex serves as a critical effector of c-Myc in activating transcription of its target genes, illuminating long-standing questions on how c-Myc drives carcinogenesis. PMID:26719542

  9. A proteomic study of cMyc improvement of CHO culture

    Directory of Open Access Journals (Sweden)

    Dunn Michael J

    2010-03-01

    Full Text Available Abstract Background The biopharmaceutical industry requires cell lines to have an optimal proliferation rate and a high integral viable cell number resulting in a maximum volumetric recombinant protein product titre. Nutrient feeding has been shown to boost cell number and productivity in fed-batch culture, but cell line engineering is another route one may take to increase these parameters in the bioreactor. The use of CHO-K1 cells with a c-myc plasmid allowing for over-expressing c-Myc (designated cMycCHO gives a higher integral viable cell number. In this study the differential protein expression in cMycCHO is investigated using two-dimensional gel electrophoresis (2-DE followed by image analysis to determine the extent of the effect c-Myc has on the cell and the proteins involved to give the new phenotype. Results Over 100 proteins that were differentially expressed in cMycCHO cells were detected with high statistical confidence, of which 41 were subsequently identified by tandem mass spectrometry (LC-MS/MS. Further analysis revealed proteins involved in a variety of pathways. Some examples of changes in protein expression include: an increase in nucleolin, involved in proliferation and known to aid in stabilising anti-apoptotic protein mRNA levels, the cytoskeleton and mitochondrial morphology (vimentin, protein biosysnthesis (eIF6 and energy metabolism (ATP synthetase, and a decreased regulation of all proteins, indentified, involved in matrix and cell to cell adhesion. Conclusion These results indicate several proteins involved in proliferation and adhesion that could be useful for future approaches to improve proliferation and decrease adhesion of CHO cell lines which are difficult to adapt to suspension culture.

  10. Perturbation of 14q32 miRNAs-cMYC gene network in osteosarcoma.

    Science.gov (United States)

    Thayanithy, Venugopal; Sarver, Aaron L; Kartha, Reena V; Li, Lihua; Angstadt, Andrea Y; Breen, Matthew; Steer, Clifford J; Modiano, Jaime F; Subramanian, Subbaya

    2012-01-01

    Osteosarcoma (OS) is the common histological form of primary bone cancer and one of the leading aggressive cancers in children under age fifteen. Although several genetic predisposing conditions have been associated with OS the understanding of its molecular etiology is limited. Here, we show that microRNAs (miRNAs) at the chr.14q32 locus are significantly downregulated in osteosarcoma compared to normal bone tissues. Bioinformatic predictions identified that a subset of 14q32 miRNAs (miR-382, miR-369-3p, miR-544 and miR-134) could potentially target cMYC transcript. The physical interaction between these 14q32 miRNAs and cMYC was validated using reporter assays. Further, restoring expression of these four 14q32 miRNAs decreased cMYC levels and induced apoptosis in Saos2 cells. We also show that exogenous expression of 14q32 miRNAs in Saos2 cells significantly downregulated miR-17-92, a transcriptional target of cMYC. The pro-apoptotic effect of 14q32 miRNAs in Saos2 cells was rescued either by overexpression of cMYC cDNA without the 3'UTR or with miR-17-92 cluster. Further, array comparative genomic hybridization studies showed no DNA copy number changes at 14q32 locus in OS patient samples suggesting that downregulation of 14q32 miRNAs are not due to deletion at this locus. Together, our data support a model where the deregulation of a network involving 14q32 miRNAs, cMYC and miR-17-92 miRNAs could contribute to osteosarcoma pathogenesis.

  11. Intragenic pausing and anti-sense transcription within the murine c-myc locus.

    OpenAIRE

    Nepveu, A; Marcu, K B

    1986-01-01

    We present a detailed analysis of strand-specific transcription in different regions of the murine c-myc locus. In normal and transformed cell lines, RNA polymerase II directed transcription occurs in the sense and anti-sense direction. Three noncontiguous regions show a high level of transcription in the anti-sense orientation: upstream of the first exon, within the first intron and in the 3' part of the gene (intron 2 and exon 3). In a cell line carrying a c-myc amplification (54c12), anti-...

  12. Ikaros and Aiolos Inhibit Pre-B-Cell Proliferation by Directly Suppressing c-Myc Expression▿

    OpenAIRE

    Ma, Shibin; Pathak, Simanta; Mandal, Malay; Trinh, Long; Clark, Marcus R.; Lu, Runqing

    2010-01-01

    Pre-B-cell expansion is driven by signals from the interleukin-7 receptor and the pre-B-cell receptor and is dependent on cyclin D3 and c-Myc. We have shown previously that interferon regulatory factors 4 and 8 induce the expression of Ikaros and Aiolos to suppress pre-B-cell proliferation. However, the molecular mechanisms through which Ikaros and Aiolos exert their growth inhibitory effect remain to be determined. Here, we provide evidence that Aiolos and Ikaros bind to the c-Myc promoter i...

  13. Cloning and characterization of a human c-myc promoter-binding protein.

    OpenAIRE

    Ray, R; Miller, D M

    1991-01-01

    A human cDNA clone encoding a c-myc promoter-binding protein was detected by screening a HeLa cell lambda phage expression cDNA library. The library was screened by using an XhoI-NaeI human c-myc P2 promoter fragment as a probe. The recombinant phage encoded a fusion protein, myc-binding protein 1 (MBP-1), which had an apparent molecular size of 40 kDa. A corresponding protein with a molecular size of 35 kDa was present in a HeLa cell extract. Sequence analysis of the cloned gene reveals an o...

  14. Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation.

    Directory of Open Access Journals (Sweden)

    Xiao-Na Pan

    Full Text Available Nowadays, drug resistance still represents a major obstacle to successful acute myeloid leukemia (AML treatment and the underlying mechanism is not fully elucidated. Here, we found that high expression of c-Myc was one of the cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc over-expression in leukemic cells induced resistance to chemotherapeutic drugs, enhanced colony formation capacity and inhibited cell differentiation induced by all-trans retinoic acid (ATRA. Meanwhile, inhibition of c-Myc by shRNA or specific c-Myc inhibitor 10058-F4 rescued the sensitivity to cytotoxic drugs, restrained the colony formation ability and promoted differentiation. RT-PCR and western blotting analysis showed that down-regulation of C/EBPβ contributed to the poor differentiation state of leukemic cells induced by c-Myc over-expression. Importantly, over-expression of C/EBPβ could reverse c-Myc induced drug resistance. In primary AML cells, the c-Myc expression was negatively correlated with C/EBPβ. 10058-F4, displayed anti-proliferative activity and increased cellular differentiation with up-regulation of C/EBPβ in primary AML cells. Thus, our study indicated that c-Myc could be a novel target to overcome drug resistance, providing a new approach in AML therapy.

  15. DOWN-REGULATION OF C-MYC ONCOGENE DURING NGF-INDUCED DIFFERENTIATION OF NEUROBLASTOMA CELL LINES

    Institute of Scientific and Technical Information of China (English)

    陈杰; 刘彤华; AlonzoHRoss

    1994-01-01

    There may be a close relationship between myc oncogenes and carcinogenesis of human neuroblastoma.In previous studies.we were able to induce differentiation of certain neuroblastoma cell lines with NGF.In order to study gene regulation during differentiation.N-myc and c-myc cDNA probes were hybridized with RNA extracted from different cell lines before and after NGF treatment.It was found that cell lines which expressed N-myc did not express cmyc while those with c-myc did not express N-myc except for SHEP cell line which had neither c-myc nor N-myc expression.In NGF-induced differentiated neurblastoma cells,c-myc oncogene was down-regulated in comparison with the control samples.The time course of c-myc down-regulation was concomitant with the apperarance of orphological differentiation.In situ hybridization also showed remarkable reduction of c-myc oncogene expression in NGF-induced differentiated cells as compared with the untreated control cells.These results in dicate that down-regulation of c-myc concogene may be a key event during NGF-induced differentiation and overexpression of c-myc oncogene may ,at least partially,be responsible for the genesis of neuroblastoma.

  16. c-Myc is a novel target of cell cycle arrest by honokiol in prostate cancer cells.

    Science.gov (United States)

    Hahm, Eun-Ryeong; Singh, Krishna Beer; Singh, Shivendra V

    2016-09-01

    Honokiol (HNK), a highly promising phytochemical derived from Magnolia officinalis plant, exhibits in vitro and in vivo anticancer activity against prostate cancer but the underlying mechanism is not fully clear. This study was undertaken to delineate the role of c-Myc in anticancer effects of HNK. Exposure of prostate cancer cells to plasma achievable doses of HNK resulted in a marked decrease in levels of total and/or phosphorylated c-Myc protein as well as its mRNA expression. We also observed suppression of c-Myc protein in PC-3 xenografts upon oral HNK administration. Stable overexpression of c-Myc in PC-3 and 22Rv1 cells conferred significant protection against HNK-mediated growth inhibition and G0-G1 phase cell cycle arrest. HNK treatment decreased expression of c-Myc downstream targets including Cyclin D1 and Enhancer of Zeste Homolog 2 (EZH2), and these effects were partially restored upon c-Myc overexpression. In addition, PC-3 and DU145 cells with stable knockdown of EZH2 were relatively more sensitive to growth inhibition by HNK compared with control cells. Finally, androgen receptor overexpression abrogated HNK-mediated downregulation of c-Myc and its targets particularly EZH2. The present study indicates that c-Myc, which is often overexpressed in early and late stages of human prostate cancer, is a novel target of prostate cancer growth inhibition by HNK.

  17. The reducing agent Dithiothreitol (DTT) increases expression of c-myc and c- fos protooncogenes in human cells

    DEFF Research Database (Denmark)

    Skouv, J.; Sørensen, Ilona Kryspin; Frandsen, H.;

    1995-01-01

    . The genes were two proto-oncogenes, c-fos and c-myc, and the tumour suppressor gene, p53. We observed that the expression of the c-fos and c-myc genes was induced when human bladder epithelial cells were treated with a standard solution of N-OH-PhIP and dithiothreitol (DTT), previously shown to be genotoxic...

  18. c-MYC responds to glucose deprivation in a cell-type-dependent manner.

    Science.gov (United States)

    Wu, S; Yin, X; Fang, X; Zheng, J; Li, L; Liu, X; Chu, L

    2015-01-01

    Metabolic reprogramming supports cancer cells' demands for rapid proliferation and growth. Previous work shows that oncogenes, such as MYC, hypoxia-inducible factor 1 (HIF1), have a central role in driving metabolic reprogramming. A lot of metabolic enzymes, which are deregulated in most cancer cells, are the targets of these oncogenes. However, whether metabolic change affects these oncogenes is still unclear. Here we show that glucose deprivation (GD) affects c-MYC protein levels in a cell-type-dependent manner regardless of P53 mutation status. GD dephosphorylates and then decreases c-MYC protein stability through PI3K signaling pathway in HeLa cells, but not in MDA-MB-231 cells. Role of c-MYC in sensitivity of GD also varies with cell types. c-MYC-mediated glutamine metabolism partially improves the sensitivity of GD in MDA-MB-231 cells. Our results reveal that the heterogeneity of cancer cells in response to metabolic stress should be considered in metabolic therapy for cancer. PMID:27551483

  19. Metformin elicits anticancer effects through the sequential modulation of DICER and c-MYC.

    Science.gov (United States)

    Blandino, Giovanni; Valerio, Mariacristina; Cioce, Mario; Mori, Federica; Casadei, Luca; Pulito, Claudio; Sacconi, Andrea; Biagioni, Francesca; Cortese, Giancarlo; Galanti, Sergio; Manetti, Cesare; Citro, Gennaro; Muti, Paola; Strano, Sabrina

    2012-01-01

    Diabetic patients treated with metformin have a reduced incidence of cancer and cancer-related mortality. Here we show that metformin affects engraftment and growth of breast cancer tumours in mice. This correlates with the induction of metabolic changes compatible with clear anticancer effects. We demonstrate that microRNA modulation underlies the anticancer metabolic actions of metformin. In fact, metformin induces DICER expression and its effects are severely impaired in DICER knocked down cells. Conversely, ectopic expression of DICER recapitulates the effects of metformin in vivo and in vitro. The microRNAs upregulated by metformin belong mainly to energy metabolism pathways. Among the messenger RNAs downregulated by metformin, we found c-MYC, IRS-2 and HIF1alpha. Downregulation of c-MYC requires AMP-activated protein kinase-signalling and mir33a upregulation by metformin. Ectopic expression of c-MYC attenuates the anticancer metabolic effects of metformin. We suggest that DICER modulation, mir33a upregulation and c-MYC targeting have an important role in the anticancer metabolic effects of metformin. PMID:22643892

  20. Selective recognition of c-MYC G-quadruplex DNA using prolinamide derivatives.

    Science.gov (United States)

    Chauhan, Ajay; Paladhi, Sushovan; Debnath, Manish; Dash, Jyotirmayee

    2016-06-28

    Herein we report the design, synthesis, biophysical and biological evaluation of triazole containing prolinamide derivatives as selective c-MYC G-quadruplex binding ligands. A modular synthetic route has been devised for prolinamide derivatives using a copper(i) catalyzed azide-alkyne cycloaddition (CuAAC). The Förster resonance energy transfer (FRET) melting assay indicates that prolinamide trimers can significantly stabilize G-quadruplex structures over duplex DNA compared to prolinamide dimers. The fluorescent intercalator displacement (FID) assay shows that a trimer with prolinamide side chains at the para-position of the benzene ring can discriminate between different quadruplex structures and exhibits the highest binding affinity towards the c-MYC G-quadruplex structure. Molecular modeling studies reveal that the prolinamide trimer stacks upon the terminal G-quartet of the c-MYC G-quadruplex. Atomic force microscopy (AFM) analysis reveals that the tris-prolinamide ligand can be used to regulate the assembly of novel supramolecular nanoarchitectures. Further, in vitro cellular studies with human hepatocellular carcinoma (HepG2) cells indicate that the tris-prolinamide derivatives can inhibit cell proliferation and reduce c-MYC expression in cancer cells. PMID:26963597

  1. Astroglial c-Myc overexpression predisposes mice to primary malignant gliomas

    DEFF Research Database (Denmark)

    Jensen, Niels Aagaard; Pedersen, Karen-Marie; Lihme, Frederikke;

    2003-01-01

    Malignant astrocytomas are common human primary brain tumors that result from neoplastic transformation of astroglia or their progenitors. Here we show that deregulation of the c-Myc pathway in developing astroglia predisposes mice to malignant astrocytomas within 2-3 weeks of age. The geneticall...

  2. Dose-adjusted Chemotherapy for Untreated c-MYC-positive Lymphoma

    Science.gov (United States)

    In this trial, adult patients with newly diagnosed Burkitt lymphoma or c-MYC-positive DLBCL will be separated into low-risk and high-risk groups; those in the low-risk group will be treated with at least three cycles of dose-adjusted EPOCH-R

  3. Alteration of microRNAs regulated by c-Myc in Burkitt lymphoma.

    Directory of Open Access Journals (Sweden)

    Anna Onnis

    Full Text Available BACKGROUND: Burkitt lymphoma (BL is an aggressive B-cell lymphoma, with a characteristic clinical presentation, morphology and immunophenotype. Over the past years, the typical translocation t(8;14 and its variants have been considered the molecular hallmark of this tumor. However, BL cases with no detectable MYC rearrangement have been identified. Intriguingly, these cases express MYC at levels comparable with cases carrying the translocation. In normal cells c-Myc expression is tightly regulated through a complex feedback loop mechanism. In cancer, MYC is often dysregulated, commonly due to genomic abnormalities. It has recently emerged that this phenomenon may rely on an alteration of post-transcriptional regulation mediated by microRNAs (miRNAs, whose functional alterations are associated with neoplastic transformation. It is also emerging that c-Myc modulates miRNA expression, revealing an intriguing crosstalk between c-Myc and miRNAs. PRINCIPAL FINDINGS: Here, we investigated the expression of miRNAs possibly regulated by c-Myc in BL cases positive or negative for the translocation. A common trend of miRNA expression, with the exception of hsa-miR-9*, was observed in all of the cases. Intriguingly, down-regulation of this miRNA seems to specifically identify a particular subset of BL cases, lacking MYC translocation. Here, we provided evidence that hsa-miR-9-1 gene is heavily methylated in those cases. Finally, we showed that hsa-miR-9* is able to modulate E2F1 and c-Myc expression. CONCLUSIONS: Particularly, this study identifies hsa-miR-9* as potentially relevant for malignant transformation in BL cases with no detectable MYC translocation. Deregulation of hsa-miR-9* may therefore be useful as a diagnostic tool, suggesting it as a promising novel candidate for tumor cell marker.

  4. Oncogene amplification detected by in situ hybridization in radiation induced rat skin tumors. [C-myc:a3

    Energy Technology Data Exchange (ETDEWEB)

    Yi Jin.

    1991-02-01

    Oncogene activation may play an important role in radiation induced carcinogenesis. C-myc oncogene amplification was detected by in situ hybridization in radiation-induced rat skin tumors, including squamous and basal cell carcinomas. In situ hybridization was performed with a biotinylated human c-myc third exon probe, visualized with an avidin-biotinylated alkaline phosphate detection system. No c-myc oncogene amplification was detected in normal rat skin at very early times after exposure to ionizing radiation, which is consistent with the view that c-myc amplification is more likely to be related to carcinogenesis than to normal cell proliferation. The incorporation of tritiated thymidine into the DNA of rat skin cells showed that the proliferation of epidermal cells reached a peak on the seventh day after exposure to ionizing radiation and then decreased. No connection between the proliferation of epidermal cell and c-myc oncogene amplification in normal or irradiated rat skin was found. The results indicated that c-myc amplification as measured by in situ hybridization was correlated with the Southern bolt results, but only some of the cancer cells were amplified. The c-myc positive cells were distributed randomly within regions of the tumor and exhibited a more uniform nuclear structure in comparison to the more vacuolated c-myc negative cells. No c-myc signal was detected in unirradiated normal skin or in irradiated skin cells near the tumors. C-myc amplification appears to be cell or cell cycle specific within radiation-induced carcinomas. 28 refs., 3 figs., 3 tabs.

  5. Driving gradual endogenous c-myc overexpression by flow-sorting: intracellular signaling and tumor cell phenotype correlate with oncogene expression

    DEFF Research Database (Denmark)

    Knudsen, Kasper Jermiin; Holm, G.M.N.; Krabbe, J.S.;

    2009-01-01

    Insulin-exposed rat mammary cancer cells were flow sorted based on a c-myc reporter plasmid encoding a destabilized green fluorescent protein. Sorted cells exhibited gradual increases in c-myc levels. Cells overexpressing c-myc by only 10% exhibited phenotypic changes attributable to c-myc overex...... an alternative modeling of the receptor-mediated carcinogenic process, compared to the currently used approaches of recombinant constitutive or conditional overexpression of oncogenic transmembrane receptor tyrosine kinases or oncogenic transcription factors....

  6. Alterations of c-Myc and c-erbB-2 genes in ovarian tumours

    Directory of Open Access Journals (Sweden)

    Pastor Tibor

    2009-01-01

    Full Text Available Introduction. According to clinical and epidemiological studies, ovarian cancer ranks fifth in cancer deaths among women. The causes of ovarian cancer remain largely unknown but various factors may increase the risk of developing it, such as age, family history of cancer, childbearing status etc. This cancer results from a succession of genetic alterations involving oncogenes and tumour suppressor genes, which have a critical role in normal cell growth regulation. Mutations and/or overexpression of three oncogenes, c-erbB-2, c-Myc and K-ras, and of the tumour suppressor gene p53, have been frequently observed in a sporadic ovarian cancer. Objective. The aim of the present study was to analyze c-Myc and c-erbB-2 oncogene alterations, specifically amplification, as one of main mechanisms of their activation in ovarian cancers and to establish a possible association with the pathogenic process. Methods. DNA was isolated from 15 samples of malignant and 5 benign ovarian tumours, using proteinase K digestion, followed by phenol-chloroform isoamyl extraction and ethanol precipitation. C-Myc and c-erbB-2 amplification were detected by differential PCR. The level of gene copy increase was measured using the Scion image software. Results. The amplification of both c-Myc and c-erbB-2 was detected in 26.7% of ovarian epithelial carcinoma specimens. Only one tumour specimen concomitantly showed increased gene copy number for both studied genes. Interestingly, besides amplification, gene deletion was also detected (26.7% for c-erbB-2. Most of the ovarian carcinomas with alterations in c-Myc and c-erbB-2 belonged to advanced FIGO stages. Conclusion. The amplification of c-Myc and c-erbB-2 oncogenes in ovarian epithelial carcinomas is most probably a late event in the pathogenesis conferring these tumours a more aggressive biological behaviour. Similarly, gene deletions point to genomic instability in epithelial carcinomas in higher clinical stages as the

  7. Cell growth suppression by thanatos-associated protein 11(THAP11) is mediated by transcriptional downregulation of c-Myc.

    Science.gov (United States)

    Zhu, C-Y; Li, C-Y; Li, Y; Zhan, Y-Q; Li, Y-H; Xu, C-W; Xu, W-X; Sun, H B; Yang, X-M

    2009-03-01

    Thanatos-associated proteins (THAPs) are zinc-dependent, sequence-specific DNA-binding factors involved in cell proliferation, apoptosis, cell cycle, chromatin modification and transcriptional regulation. THAP11 is the most recently described member of this human protein family. In this study, we show that THAP11 is ubiquitously expressed in normal tissues and frequently downregulated in several human tumor tissues. Overexpression of THAP11 markedly inhibits growth of a number of different cells, including cancer cells and non-transformed cells. Silencing of THAP11 by RNA interference in HepG2 cells results in loss of cell growth repression. These results suggest that human THAP11 may be an endogenous physiologic regulator of cell proliferation. We also provide evidence that the function of THAP11 is mediated by its ability to repress transcription of c-Myc. Promoter reporter assays indicate a DNA binding-dependent c-Myc transcriptional repression. Chromatin immunoprecipitations and EMSA assay suggest that THAP11 directly binds to the c-Myc promoter. The findings that expression of c-Myc rescues significantly cells from THAP11-mediated cell growth suppression and that THAP11 expression only slightly inhibits c-Myc null fibroblasts cells growth reveal that THAP11 inhibits cell growth through downregulation of c-Myc expression. Taken together, these suggest that THAP11 functions as a cell growth suppressor by negatively regulating the expression of c-Myc. PMID:19008924

  8. Repression of c-Myc responsive genes in cycling cells causes G1 arrest through reduction of cyclin E/CDK2 kinase activity

    NARCIS (Netherlands)

    Berns, K.; Hijmans, E.M.; Bernards, R.A.

    1997-01-01

    The c-myc gene encodes a sequence-specific DNA binding protein involved in proliferation and oncogenesis. Activation of c-myc expression in quiescent cells is sufficient to mediate cell cycle entry, whereas inhibition of c-myc expression causes cycling cells to withdraw from the cell cycle. To searc

  9. Aspirin and salicylic acid decrease c-Myc expression in cancer cells: a potential role in chemoprevention.

    Science.gov (United States)

    Ai, Guoqiang; Dachineni, Rakesh; Muley, Pratik; Tummala, Hemachand; Bhat, G Jayarama

    2016-02-01

    Epidemiological studies have demonstrated a significant correlation between regular aspirin use and reduced colon cancer incidence and mortality; however, the pathways by which it exerts its anti-cancer effects are still not fully explored. We hypothesized that aspirin's anti-cancer effect may occur through downregulation of c-Myc gene expression. Here, we demonstrate that aspirin and its primary metabolite, salicylic acid, decrease the c-Myc protein levels in human HCT-116 colon and in few other cancer cell lines. In total cell lysates, both drugs decreased the levels of c-Myc in a concentration-dependent fashion. Greater inhibition was observed in the nucleus than the cytoplasm, and immunofluorescence studies confirmed these observations. Pretreatment of cells with lactacystin, a proteasome inhibitor, partially prevented the downregulatory effect of both aspirin and salicylic acid, suggesting that 26S proteasomal pathway is involved. Both drugs failed to decrease exogenously expressed DDK-tagged c-Myc protein levels; however, under the same conditions, the endogenous c-Myc protein levels were downregulated. Northern blot analysis showed that both drugs caused a decrease in c-Myc mRNA levels in a concentration-dependent fashion. High-performance liquid chromatography (HPLC) analysis showed that aspirin taken up by cells was rapidly metabolized to salicylic acid, suggesting that aspirin's inhibitory effect on c-Myc may occur through formation of salicylic acid. Our result suggests that salicylic acid regulates c-Myc level at both transcriptional and post-transcription levels. Inhibition of c-Myc may represent an important pathway by which aspirin exerts its anti-cancer effect and decrease the occurrence of cancer in epithelial tissues. PMID:26314861

  10. Design of a novel triple helix-forming oligodeoxyribonucleotide directed to the major promoter of the c-myc gene

    OpenAIRE

    McGuffie, E M; Catapano, C. V.

    2002-01-01

    Altered expression of c-myc is implicated in pathogenesis and progression of many human cancers. Triple helix-forming oligonucleotides (TFOs) directed to a polypurine/polypyrimidine sequence in a critical regulatory region near the c-myc P2 promoter have been shown to inhibit c-myc transcription in vitro and in cells. However, these guanine-rich TFOs had moderate binding affinity and required high concentrations for activity. The 23 bp myc P2 sequence is split equally into AT- and GC-rich tra...

  11. Knockdown of c-Myc expression by RNAi inhibits MCF-7 breast tumor cells growth in vitro and in vivo

    International Nuclear Information System (INIS)

    Breast cancer is the leading cause of cancer death in women worldwide. Elevated expression of c-Myc is a frequent genetic abnormality seen in this malignancy. For a better understanding of its role in maintaining the malignant phenotype, we used RNA interference (RNAi) directed against c-Myc in our study. RNAi provides a new, reliable method to investigate gene function and has the potential for gene therapy. The aim of the study was to examine the anti-tumor effects elicited by a decrease in the protein level of c-Myc by RNAi and its possible mechanism of effects in MCF-7 cells. A plasmid-based polymerase III promoter system was used to deliver and express short interfering RNA (siRNA) targeting c-myc to reduce its expression in MCF-7 cells. Western blot analysis was used to measure the protein level of c-Myc. We assessed the effects of c-Myc silencing on tumor growth by a growth curve, by soft agar assay and by nude mice experiments in vivo. Standard fluorescence-activated cell sorter analysis and TdT-mediated dUTP nick end labelling assay were used to determine apoptosis of the cells. Our data showed that plasmids expressing siRNA against c-myc markedly and durably reduced its expression in MCF-7 cells by up to 80%, decreased the growth rate of MCF-7 cells, inhibited colony formation in soft agar and significantly reduced tumor growth in nude mice. We also found that depletion of c-Myc in this manner promoted apoptosis of MCF-7 cells upon serum withdrawal. c-Myc has a pivotal function in the development of breast cancer. Our data show that decreasing the c-Myc protein level in MCF-7 cells by RNAi could significantly inhibit tumor growth both in vitro and in vivo, and imply the therapeutic potential of RNAi on the treatment of breast cancer by targeting overexpression oncogenes such as c-myc, and c-myc might be a potential therapeutic target for human breast cancer

  12. Coding elements in exons 2 and 3 target c-myc mRNA downregulation during myogenic differentiation.

    OpenAIRE

    Yeilding, N M; W.M. Lee

    1997-01-01

    Downregulation in expression of the c-myc proto-oncogene is an early molecular event in differentiation of murine C2C12 myoblasts into multinucleated myotubes. During differentiation, levels of c-myc mRNA decrease 3- to 10-fold despite a lack of change in its transcription rate. To identify cis-acting elements that target c-myc mRNA for downregulation during myogenesis, we stably transfected C2C12 cells with mutant myc genes or chimeric genes in which various myc sequences were fused to the h...

  13. Site-Specific Oligonucleotide Binding Represses Transcription of the Human c-myc Gene in vitro

    Science.gov (United States)

    Cooney, Michael; Czernuszewicz, Graznya; Postel, Edith H.; Flint, S. Jane; Hogan, Michael E.

    1988-07-01

    A 27-base-long DNA oligonucleotide was designed that binds to duplex DNA at a single site within the 5' end of the human c-myc gene, 115 base pairs upstream from the transcription origin P1. On the basis of the physical properties of its bound complex, it was concluded that the oligonucleotide forms a colinear triplex with the duplex binding site. By means of an in vitro assay system, it was possible to show a correlation between triplex formation at -115 base pairs and repression of c-myc transcription. The possibility is discussed that triplex formation (site-specific RNA binding to a DNA duplex) could serve as the basis for an alternative program of gene control in vivo.

  14. The c-myc coding DNA sequences of cyprinids (Teleostei: Cypriniformes): Implications for phylogeny

    Institute of Scientific and Technical Information of China (English)

    KONG XiangHui; WANG XuZhen; GAN XiaoNi; HE ShunPing

    2007-01-01

    The family Cyprinidae is one of the largest fish families in the world, which is widely distributed in East Asian, with obvious difference in characteristic size among species. The phylogenetic analysis of cyprinid taxa based on the functionally important genes can help to understand the speciation and functional divergence of the Cyprinidae. The c-myc gene is an important gene regulating individual growth.In the present study, the sequence variations of the cyprinid c-myc gene and their phylogenetic significance were analyzed. The 41 complete sequences of the c-myc gene were obtained from cyprinids and outgroups through PCR amplification and clone. The coding DNA sequences of the c-myc gene were used to infer molecular phylogenetic relationships within the Cyprinidae. Myxocyprinus asiaticus (Catostomidae), Misgurnus anguillicaudatus (Cobitidae) and Hemimyzon sinensis (Homalopteridae)were assigned to the outgroup taxa. Phylogenetic analyses using maximum parsimony (MP), maximum likelihood (ML), and Bayesian retrieved similar topology. Within the Cyprinidae, Leuciscini and Barbini formed the monophyletic lineage respectively with high nodal supports. Leuciscini comprises Xenocyprinae, Cultrinae, East Asian species of Leuciscinae and Danioninae, Gobioninae and Acheilognathinae, and Barbini contains Schizothoracinae, Barbinae, Cyprininae and Labeoninae. Danio rerio, D.myersi and Rasbora trilineata were supposed to separate from Leuciscinae and Barbini and to form another lineage. The positions of some Danioninae species were still unresolved. Analyses of both amino acid variation with parsimony information and two high variation regions indicated that there is no correlation between variations of single amino acid or high variation regions and characteristic size of cyprinids. In addition, the species with smaller size were usually found to be basal within clades in the tree, which might be the results of the adaptation to the primitive ecology and survival pressure.

  15. Antitumor activity of the c-Myc inhibitor KSI-3716 in gemcitabine-resistant bladder cancer

    OpenAIRE

    Seo, Ho Kyung; Ahn, Kyung-Ohk; Jung, Nae-Rae; Shin, Ji-Sun; Park, Weon Seo; Lee, Kang Hyun; Lee, Sang-Jin; Jeong, Kyung-Chae

    2014-01-01

    Intravesical instillation of chemotherapeutic agents is a well-established treatment strategy to decrease recurrence following transurethral resection in non-muscle invasive bladder cancer. Gemcitabine is a recently developed treatment option. However, the curative effects of gemcitabine are far from satisfactory due to de novo or acquired drug resistance. In a previous study, we reported that intravesical administration of the c-Myc inhibitor KSI-3716 suppresses tumor growth in an orthotopic...

  16. Mode of c-myc protein expression in Spitz nevi, common melanocytic nevi and malignant melanomas.

    Science.gov (United States)

    Bergman, R; Lurie, M; Kerner, H; Kilim, S; Friedman-Birnbaum, R

    1997-04-01

    The expression of c-myc protein was studied in formalin-fixed, paraffin-embedded sections of 16 compound Spitz nevi (SNs), 20 ordinary compound melanocytic nevi (MNs) and 30 malignant melanomas (MMs), using monoclonal antibody 9E10 and an immunoperoxidase technique. Nine (56%) SNs, 16 (80%) MNs and 23 (77%) MMs showed positive reactions in some of the tumor cells (P = non-significant). The staining reactions were mostly cytoplasmic, and moderate to strong in intensity. The frequencies of positively stained cells were higher in the MN and SN groups. Most of the lesions with a significant dermal component did not show stratification of staining with progressive descent into the dermis. Therefore, the mode of expression of c-myc in routinely processed specimens does not differentiate between SNs, MNs and MMs. One possible reason is that the increased expression of the c-myc protein is not sufficient alone to promote proliferation and malignant transformation in these types of tumors. PMID:9138112

  17. Temporal Requirements of cMyc Protein for Reprogramming Mouse Fibroblasts

    Directory of Open Access Journals (Sweden)

    Corey Heffernan

    2012-01-01

    Full Text Available Exogenous expression of Oct4, Sox2, Klf4, and cMyc forces mammalian somatic cells to adopt molecular and phenotypic characteristics of embryonic stem cells, commencing with the required suppression of lineage-associated genes (e.g., Thy1 in mouse. Although omitting cMyc from the reprogramming cocktail minimizes risks of uncontrolled proliferation, its exclusion results in fold reductions in reprogramming efficiency. Thus, the feasibility of substituting cMyc transgene with (non-integrative recombinant “pTAT-mcMyc” protein delivery was assessed, without compromising reprogramming efficiency or the pluripotent phenotype. Purification and delivery of semisoluble/particulate pTAT-mcMyc maintained Oct4-GFP+ colony formation (i.e., reprogramming efficiency whilst supporting pluripotency by various criteria. Differential repression of Thy1 by pTAT-mcMyc ± Oct4, Sox2, and Klf4 (OSK suggested differential (and non-additive mechanisms of repression. Extending these findings, attempts to enhance reprogramming efficiency through a staggered approach (prerepression of Thy1 failed to improve reprogramming efficiency. We consider protein delivery a useful tool to decipher temporal/molecular events characterizing somatic cell reprogramming.

  18. A role for transcriptional repression of p21CIP1 by c-Myc in overcoming transforming growth factor β-induced cell-cycle arrest

    OpenAIRE

    Claassen, Gisela F.; Hann, Stephen R.

    2000-01-01

    c-Myc plays a vital role in cell-cycle progression. Deregulated expression of c-Myc can overcome cell-cycle arrest in order to promote cellular proliferation. Transforming growth factor β (TGFβ) treatment of immortalized human keratinocyte cells inhibits cell-cycle progression and is characterized by down-regulation of c-Myc followed by up-regulation of p21CIP1. A direct role of c-Myc in this pathway was demonstrated by the observation that ectopic expression of c-Myc overcame the cell-cycle ...

  19. c-MYC expression sensitizes medulloblastoma cells to radio- and chemotherapy and has no impact on response in medulloblastoma patients

    International Nuclear Information System (INIS)

    To study whether and how c-MYC expression determines response to radio- and chemotherapy in childhood medulloblastoma (MB). We used DAOY and UW228 human MB cells engineered to stably express different levels of c-MYC, and tested whether c-MYC expression has an effect on radio- and chemosensitivity using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium inner salt (MTS) assay, clonogenic survival, apoptosis assays, cell cycle analysis, and western blot assessment. In an effort to validate our results, we analyzed c-MYC mRNA expression in formalin-fixed paraffin-embedded tumor samples from well-documented patients with postoperative residual tumor and compared c-MYC mRNA expression with response to radio- and chemotherapy as examined by neuroradiological imaging. In DAOY - and to a lesser extent in UW228 - cells expressing high levels of c-MYC, the cytotoxicity of cisplatin, and etoposide was significantly higher when compared with DAOY/UW228 cells expressing low levels of c-MYC. Irradiation- and chemotherapy-induced apoptotic cell death was enhanced in DAOY cells expressing high levels of c-MYC. The response of 62 of 66 residual tumors was evaluable and response to postoperative radio- (14 responders (CR, PR) vs. 5 non-responders (SD, PD)) or chemotherapy (23 CR/PR vs. 20 SD/PD) was assessed. c-MYC mRNA expression was similar in primary MB samples of responders and non-responders (Mann-Whitney U test, p = 0.50, ratio 0.49, 95% CI 0.008-30.0 and p = 0.67, ratio 1.8, 95% CI 0.14-23.5, respectively). c-MYC sensitizes MB cells to some anti-cancer treatments in vitro. As we failed to show evidence for such an effect on postoperative residual tumors when analyzed by imaging, additional investigations in xenografts and larger MB cohorts may help to define the exact function of c-MYC in modulating response to treatment

  20. Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder

    Science.gov (United States)

    Massari, Francesco; Bria, Emilio; Ciccarese, Chiara; Munari, Enrico; Modena, Alessandra; Zambonin, Valentina; Sperduti, Isabella; Artibani, Walter; Cheng, Liang; Martignoni, Guido; Tortora, Giampaolo; Brunelli, Matteo

    2015-01-01

    Background To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential. Methods In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0–3); c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive. Results beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively); 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02) and c-Myc 28 low vs 8 high (p-value 0.007). Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006). Conclusions c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies. PMID:26046361

  1. Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder.

    Directory of Open Access Journals (Sweden)

    Francesco Massari

    Full Text Available To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential.In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0-3; c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive.beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively; 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02 and c-Myc 28 low vs 8 high (p-value 0.007. Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006.c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies.

  2. A critical appraisal of the immunohistochemical detection of the c-myc oncogene product in colorectal cancer.

    OpenAIRE

    Jones, D J; Ghosh, A. K.; Moore, M.; Schofield, P. F.

    1987-01-01

    Expression of c-myc was studied immunohistochemically in 100 colorectal carcinomas, using a monoclonal antibody, Myc 1-6E10, which is purported to recognize the oncoprotein (p62c-myc) in paraffin-embedded material. In normal epithelium, maturing crypt cells and terminally differentiated surface cells were positive, and proliferating basal crypt cells negative. All carcinomas stained positively, but intensity was independent of histological differentiation, Dukes' stage, DNA ploidy and surviva...

  3. hTERT protein expression is independent of clinicopathological parameters and c-Myc protein expression in human breast cancer

    Directory of Open Access Journals (Sweden)

    Meligonis G

    2005-01-01

    Full Text Available Abstract Background Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal length and stability thus leading to cellular immortalisation. The hTERT (human telomerase reverse transcriptase subunit seems to be the rate-limiting determinant of telomerase and knowledge of factors controlling hTERT transcription may be useful in therapeutic strategies. The hTERT promoter contains binding sites for c-Myc and there is some experimental and in vitro evidence that c-Myc may increase hTERT expression. We previously reported no correlation between c-Myc mRNA expression and hTERT mRNA or telomerase activity in human breast cancer. This study aims to examine the correlation between hTERT expression as determined by immunohistochemistry and c-Myc expression, lymph node status, and tumour size and grade in human breast cancer. Materials and methods The immunohistochemical expression of hTERT and c-Myc was investigated in 38 malignant breast tumours. The expression of hTERT was then correlated with the lymph node status, c-Myc expression and other clinicopathological parameters of the tumours. Results hTERT expression was positive in 27 (71% of the 38 tumours. 15 (79% of 19 node positive tumours were hTERT positive compared with 11 (63% of 19 node negative tumours. The expression was higher in node positive tumours but this failed to reach statistical significance (p = 0.388. There was no significant association with tumour size, tumour grade or c-Myc expression. However, hTERT expression correlated positively with patients' age (correlation coefficient = 0.415, p = 0.0097. Conclusion hTERT protein expression is independent of lymph node status, tumour size and grade and c-Myc protein expression in human breast cancer

  4. The regulatory role of c-MYC on HDAC2 and PcG expression in human multipotent stem cells

    OpenAIRE

    Bhandari, Dilli Ram; Seo, Kwang-Won; Jung, Ji-Won; Kim, Hyung-Sik; YANG, Se-Ran; Kang, Kyung-Sun

    2011-01-01

    Abstract Myelocytomatosis oncogene (c-MYC) is a well-known nuclear oncoprotein having multiple functions in cell proliferation, apoptosis and cellular transformation. Chromosomal modification is also important to the differentiation and growth of stem cells. Histone deacethylase (HDAC) and polycomb group (PcG) family genes are well-known chromosomal modification genes. The aim of this study was to elucidate the role of c-MYC in the expression of chromosomal modification via the HDAC family ge...

  5. Expression of Wnt-1,beta-catenin and c-myc in Ovarian Epithelial Tumor and Its Implication

    Institute of Scientific and Technical Information of China (English)

    LIN Xiao; HU Zhuo-ying

    2008-01-01

    Objective:To investigate the expression of Wnt-1, beta-catenin and c-myc in normal ovarian epithelial cell and malignant ovarian epithelial tumor. Methods:Immunohistochemical staining with SP method was conducted to identify the expression of Wnt-1,beta-catenin and c-myc in 18 samples of normal epithelial tissue and 34 cases of malignant epithelial tumor of ovary. Results:The expression rate of Wnt-1 and c-myc in malignant epithelial tumors was higher than those in normal epithelial cell(P<0.05).The abnormal expression rate of beta-catenin in malignant ovarian epithelial tumors was higher than that in normal epithelial cell(P<0.05).A significant positive correlation was found between Wnt-1, beta-catenin and c-myc in malignant ovarian epithelial tumor(P<0.05).A significant difierence of expressions of Beta-catenin and C-myc was found between serous and mutinous tumors (P<0.05). Conclusion:The abnormal expression of Wnt-1,beta-catenin and c-myc might indicate the malignant transformation in ovarian epithelial tumors.

  6. BAF53 Forms Distinct Nuclear Complexes and Functions as a Critical c-Myc-Interacting Nuclear Cofactor for Oncogenic Transformation

    Science.gov (United States)

    Park, Jeonghyeon; Wood, Marcelo A.; Cole, Michael D.

    2002-01-01

    The c-Myc oncoprotein functions as a transcription factor that can transform normal cells into tumor cells, as well as playing a direct role in normal cell proliferation. The c-Myc protein transactivates cellular promoters by recruiting nuclear cofactors to chromosomal sites through an N-terminal transactivation domain. We have previously reported the identification and functional characterization of four different c-Myc cofactors: TRRAP, hGCN5, TIP49, and TIP48. Here we present the identification and characterization of the actin-related protein BAF53 as a c-Myc-interacting nuclear cofactor that forms distinct nuclear complexes. In addition to the human SWI/SNF-related BAF complex, BAF53 forms a complex with TIP49 and TIP48 and a separate biochemically distinct complex containing TRRAP and a histone acetyltransferase which does not contain TIP60. Using deletion mutants of BAF53, we show that BAF53 is critical for c-Myc oncogenic activity. Our results indicate that BAF53 plays a functional role in c-Myc-interacting nuclear complexes. PMID:11839798

  7. C-Myc negatively controls the tumor suppressor PTEN by upregulating miR-26a in glioblastoma multiforme cells

    International Nuclear Information System (INIS)

    Highlights: •The c-Myc oncogene directly upregulates miR-26a expression in GBM cells. •ChIP assays demonstrate that c-Myc interacts with the miR-26a promoter. •Luciferase reporter assays show that PTEN is a specific target of miR-26a. •C-Myc–miR-26a suppression of PTEN may regulate the PTEN/AKT pathway. •Overexpression of c-Myc enhances the proliferative capacity of GBM cells. -- Abstract: The c-Myc oncogene is amplified in many tumor types. It is an important regulator of cell proliferation and has been linked to altered miRNA expression, suggesting that c-Myc-regulated miRNAs might contribute to tumor progression. Although miR-26a has been reported to be upregulated in glioblastoma multiforme (GBM), the mechanism has not been established. We have shown that ectopic expression of miR-26a influenced cell proliferation by targeting PTEN, a tumor suppressor gene that is inactivated in many common malignancies, including GBM. Our findings suggest that c-Myc modulates genes associated with oncogenesis in GBM through deregulation of miRNAs via the c-Myc–miR-26a–PTEN signaling pathway. This may be of clinical relevance

  8. Coordinate increase of telomerase activity and c-Myc expression in Helicobacter pylori-associated gastric diseases

    Institute of Scientific and Technical Information of China (English)

    Guo-Xin Zhang; Yan-Hong Gu; Zhi-Quan Zhao; Shun-Fu Xu; Hong-Ji Zhang; Hong-Di Wang; Bo Hao

    2004-01-01

    AIM: To detect the telomerase activity and c-Myc expression in gastric diseases and to examine the relation between these values and Helicobacter pylori (H pylori) as a risk factor for gastric cancer.METHODS: One hundred and seventy-one gastric samples were studied to detect telomerase activity using a telomerase polymerase chain reaction enzyme linked immunosorbent assay (PCR-ELTSA), and c-Myc expression using immunohistochemistry.RESULTS: The telomerase activity and c-Myc expression were higher in cancers (87.69% and 61.54%) than in noncancerous tissues. They were higher in chronic atrophic gastritis with severe intestinal metaplasia (52.38% and 47.62%) than in chronic atrophic gastritis with mild intestinal metaplasia (13.33% and 16.67%). Tn chronic atrophic gastritis with severe intestinal metaplasia, the telomerase activity and c-Myc expression were higher in cases with -H pylori infection (67.86% and 67.86%) than in those without infection (21.43%and 7.14%). c-Myc expression was higher in gastric cancer with H pylori infection (77.27%) than in that without infection (28.57%). The telomerase activity and c-Nyc expression were coordinately up-regulated in H pylori infected gastric cancer and chronic atrophic gastritis with severe intestinal metaplasia.CONCLUSION: H pylori infection may influence both telomerase activity and c-Myc expression in gastric diseases,especially in chronic atrophic gastritis.

  9. C-Myc negatively controls the tumor suppressor PTEN by upregulating miR-26a in glioblastoma multiforme cells

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Pin; Nie, Quanmin; Lan, Jin; Ge, Jianwei [Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127 (China); Qiu, Yongming, E-mail: qiuzhoub@hotmail.com [Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127 (China); Shanghai Institute of Head Trauma, Shanghai 200127 (China); Mao, Qing, E-mail: maoq@netease.com [Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127 (China); Shanghai Institute of Head Trauma, Shanghai 200127 (China)

    2013-11-08

    Highlights: •The c-Myc oncogene directly upregulates miR-26a expression in GBM cells. •ChIP assays demonstrate that c-Myc interacts with the miR-26a promoter. •Luciferase reporter assays show that PTEN is a specific target of miR-26a. •C-Myc–miR-26a suppression of PTEN may regulate the PTEN/AKT pathway. •Overexpression of c-Myc enhances the proliferative capacity of GBM cells. -- Abstract: The c-Myc oncogene is amplified in many tumor types. It is an important regulator of cell proliferation and has been linked to altered miRNA expression, suggesting that c-Myc-regulated miRNAs might contribute to tumor progression. Although miR-26a has been reported to be upregulated in glioblastoma multiforme (GBM), the mechanism has not been established. We have shown that ectopic expression of miR-26a influenced cell proliferation by targeting PTEN, a tumor suppressor gene that is inactivated in many common malignancies, including GBM. Our findings suggest that c-Myc modulates genes associated with oncogenesis in GBM through deregulation of miRNAs via the c-Myc–miR-26a–PTEN signaling pathway. This may be of clinical relevance.

  10. Lack of Cyclin-Dependent Kinase 4 Inhibits c-myc Tumorigenic Activities in Epithelial Tissues

    Science.gov (United States)

    Miliani de Marval, Paula L.; Macias, Everardo; Rounbehler, Robert; Sicinski, Piotr; Kiyokawa, Hiroaki; Johnson, David G.; Conti, Claudio J.; Rodriguez-Puebla, Marcelo L.

    2004-01-01

    The proto-oncogene c-myc encodes a transcription factor that is implicated in the regulation of cellular proliferation, differentiation, and apoptosis and that has also been found to be deregulated in several forms of human and experimental tumors. We have shown that forced expression of c-myc in epithelial tissues of transgenic mice (K5-Myc) resulted in keratinocyte hyperproliferation and the development of spontaneous tumors in the skin and oral cavity. Although a number of genes involved in cancer development are regulated by c-myc, the actual mechanisms leading to Myc-induced neoplasia are not known. Among the genes regulated by Myc is the cyclin-dependent kinase 4 (CDK4) gene. Interestingly, previous studies from our laboratory showed that the overexpression of CDK4 led to keratinocyte hyperproliferation, although no spontaneous tumor development was observed. Thus, we tested the hypothesis that CDK4 may be one of the critical downstream genes involved in Myc carcinogenesis. Our results showed that CDK4 inhibition in K5-Myc transgenic mice resulted in the complete inhibition of tumor development, suggesting that CDK4 is a critical mediator of tumor formation induced by deregulated Myc. Furthermore, a lack of CDK4 expression resulted in marked decreases in epidermal thickness and keratinocyte proliferation compared to the results obtained for K5-Myc littermates. Biochemical analysis of the K5-Myc epidermis showed that CDK4 mediates the proliferative activities of Myc by sequestering p21Cip1 and p27Kip1 and thereby indirectly activating CDK2 kinase activity. These results show that CDK4 mediates the proliferative and oncogenic activities of Myc in vivo through a mechanism that involves the sequestration of specific CDK inhibitors. PMID:15314163

  11. c-Myc inhibits TP53INP1 expression via promoter methylation in esophageal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Weng, Wenhao; Yang, Qinyuan [Department of Laboratory Medicine, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Huang, Miaolong [Department of Thoracic Surgery, Yuebei People' s Hospital, Shaoguan, Guangdong 512026 (China); Qiao, Yongxia [Department of Preventive Medicine, Tongji University, Shanghai City 200092 (China); Xie, Yuan; Yu, Yongchun [Department of Laboratory Medicine, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Jing, An, E-mail: Anjing77@gmail.com [Department of Thoracic Surgery, Yuebei People' s Hospital, Shaoguan, Guangdong 512026 (China); Institute of Cancer Research, Southern Medical University, Guangzhou 510515 (China); Li, Zhi, E-mail: lizhiweng2010@163.com [Department of Laboratory Medicine, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China)

    2011-02-11

    Research highlights: {yields} TP53INP1 expression is down-regulated in esophageal carcinoma and is associated with CGI-131 methylation. {yields} Inhibition of CGI-131 methylation upregulates TP53INP1 expression in ESCC cell lines. {yields} Ectopic expression of TP53INP1 inhibits growth of ESCC cells by inducing apoptosis and inhibiting cell cycle progression. {yields} c-Myc binds to the promoter of TP53INP1 in vivo and vitro and recruits DNMT3A to TP53INP1 promoter for CGI-131 methylation. -- Abstract: Tumor protein p53-induced nuclear protein 1 (TP53INP1) is a well known stress-induced protein that plays a role in both cell cycle arrest and p53-mediated apoptosis. Loss of TP53INP1 expression has been reported in human melanoma, breast carcinoma, and gastric cancer. However, TP53INP1 expression and its regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. Our findings are in agreement with previous reports in that the expression of TP53INP1 was downregulated in 28% (10/36 cases) of ESCC lesions, and this was accompanied by significant promoter methylation. Overexpression of TP53INP1 induced G1 cell cycle arrest and increased apoptosis in ESCC cell lines (EC-1, EC-109, EC-9706). Furthermore, our study showed that the oncoprotein c-Myc bound to the core promoter of TP53INP1 and recruited DNA methyltransferase 3A to methylate the local promoter region, leading to the inhibition of TP53INP1 expression. Our findings revealed that TP53INP1 is a tumor suppressor in ESCC and that c-Myc-mediated DNA methylation-associated silencing of TP53INP1 contributed to the pathogenesis of human ESCC.

  12. In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities.

    Directory of Open Access Journals (Sweden)

    Oscar M Pello

    Full Text Available Although tumor-associated macrophages (TAMs are involved in tumor growth and metastasis, the mechanisms controlling their pro-tumoral activities remain largely unknown. The transcription factor c-MYC has been recently shown to regulate in vitro human macrophage polarization and be expressed in macrophages infiltrating human tumors. In this study, we exploited the predominant expression of LysM in myeloid cells to generate c-Myc(fl/fl LysM(cre/+ mice, which lack c-Myc in macrophages, to investigate the role of macrophage c-MYC expression in cancer. Under steady-state conditions, immune system parameters in c-Myc(fl/fl LysM(cre/+ mice appeared normal, including the abundance of different subsets of bone marrow hematopoietic stem cells, precursors and circulating cells, macrophage density, and immune organ structure. In a model of melanoma, however, TAMs lacking c-Myc displayed a delay in maturation and showed an attenuation of pro-tumoral functions (e.g., reduced expression of VEGF, MMP9, and HIF1α that was associated with impaired tissue remodeling and angiogenesis and limited tumor growth in c-Myc(fl/fl LysM(cre/+ mice. Macrophage c-Myc deletion also diminished fibrosarcoma growth. These data identify c-Myc as a positive regulator of the pro-tumoral program of TAMs and suggest c-Myc inactivation as an attractive target for anti-cancer therapy.

  13. WT1 Enhances Proliferation and Impedes Apoptosis in KRAS Mutant NSCLC via Targeting cMyc

    OpenAIRE

    Wu, Chen; Wang, Sihan; Xu, Caihua; Tyler, Andreas; Li, Xingru; Andersson, Charlotta; Oji, Yusuke; Sugiyama, Haruo; Chen, Yijiang; Li, Aihong

    2015-01-01

    Background: A novel link between oncogenic KRAS signalling and WT1 was recently identified. We sought to investigate the role of WT1 and KRAS in proliferation and apoptosis. Methods: KRAS mutations and WT1 (cMyc) expression were detected using Sanger sequencing and real-time PCR in 77 patients with non-small cell lung cancer (NSCLC). Overexpression and knockdown of WT1 were generated with plasmid and siRNA via transient transfection technology in H1299 and H1568 cells. MTT assay for detection...

  14. TCEAL7 Inhibition of c-Myc Activity in Alternative Lengthening of Telomeres Regulates hTERT Expression

    Directory of Open Access Journals (Sweden)

    Kyle Lafferty-Whyte

    2010-05-01

    Full Text Available Replicative senescence forms a major barrier to tumor progression. Cancer cells bypass this by using one of the two known telomere maintenance mechanisms: telomerase or the recombination-based alternative lengthening of telomeres (ALT mechanism. The molecular details of ALT are currently poorly understood. We have previously shown that telomerase is actively repressed through complex networks of kinase, gene expression, and chromatin regulation. In this study, we aimed to gain further understanding of the role of kinases in the regulation of telomerase expression in ALT cells. Using a whole human kinome small interfering RNA (siRNA screen, we highlighted 106 kinases whose expression is linked to human telomerase reverse transcriptase (hTERT promoter activity. Network modeling of transcriptional regulation implicated c-Myc as a key regulator of the 106 kinase hits. Given our previous observations of lower c-Myc activity in ALT cells, we further explored its potential to regulate telomerase expression in ALT. We found increased c-Myc binding at the hTERT promoter in telomerase-positive compared with ALT cells, although no expression differences in c-Myc, Mad, or Max were observed between ALT and telomerase-positive cells that could explain decreased c-Myc activity in ALT. Instead, we found increased expression of the c-Myc competitive inhibitor TCEAL7 in ALT cells and tumors and that alteration of TCEAL7 expression levels in ALT and telomerase-positive cells affects hTERT expression. Lower c-Myc activity in ALT may therefore be obtained through TCEAL7 regulation. Thus, TCEAL7 may present an interesting novel target for cancer therapy, which warrants further investigation.

  15. Erythropoietin activates two distinct signaling pathways required for the initiation and the elongation of c-myc

    Science.gov (United States)

    Chen, C.; Sytkowski, A. J.

    2001-01-01

    Erythropoietin (Epo) stimulation of erythroid cells results in the activation of several kinases and a rapid induction of c-myc expression. Protein kinase C is necessary for Epo up-regulation of c-myc by promoting elongation at the 3'-end of exon 1. PKCepsilon mediates this signal. We now show that Epo triggers two signaling pathways to c-myc. Epo rapidly up-regulated Myc protein in BaF3-EpoR cells. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 blocked Myc up-regulation in a concentration-dependent manner but had no effect on the Epo-induced phosphorylation of ERK1 and ERK2. LY294002 also had no effect on Epo up-regulation of c-fos. MEK1 inhibitor PD98059 blocked both the c-myc and the c-fos responses to Epo. PD98059 and the PKC inhibitor H7 also blocked the phosphorylation of ERK1 and ERK2. PD98059 but not LY294002 inhibited Epo induction of ERK1 and ERK2 phosphorylation in normal erythroid cells. LY294002 blocked transcription of c-myc at exon 1. PD98059 had no effect on transcription from exon 1 but, rather, blocked Epo-induced c-myc elongation at the 3'-end of exon 1. These results identify two Epo signaling pathways to c-myc, one of which is PI3K-dependent operating on transcriptional initiation, whereas the other is mitogen-activated protein kinase-dependent operating on elongation.

  16. Cadmium Activates Multiple Signaling Pathways That Coordinately Stimulate Akt Activity to Enhance c-Myc mRNA Stability.

    Directory of Open Access Journals (Sweden)

    Jia-Shiuan Tsai

    Full Text Available Cadmium is a known environmental carcinogen. Exposure of Cd leads to the activation of several proto-oncogenes in cells. We investigated here the mechanism of c-Myc expression in hepatic cells under Cd treatment. The c-Myc protein and mRNA levels increased in dose- and time-dependent manners in HepG2 cells with Cd treatment. This increase was due to an increase in c-Myc mRNA stability. To explore the mechanism involved in enhancing the mRNA stability, several cellular signaling factors that evoked by Cd treatment were analyzed. PI3K, p38, ERK and JNK were activated by Cd. However, ERK did not participate in the Cd-induced c-Myc expression. Further analysis revealed that mTORC2 was a downstream factor of p38. PI3K, JNK and mTORC2 coordinately activated Akt. Akt was phosphorylated at Thr450 in the untreated cells. Cd treatment led to additional phosphorylation at Thr308 and Ser473. Blocking any of the three signaling factors resulted in the reduction of phosphorylation level at all three Akt sites. The activated Akt phosphorylated Foxo1 and allowed the modified protein to translocate into the cytoplasm. We conclude that Cd-induced accumulation of c-Myc requires the activation of several signaling pathways. The signals act coordinately for Akt activation and drive the Foxo1 from the nucleus to the cytoplasm. Reduction of Foxo1 in the nucleus reduces the transcription of its target genes that may affect c-Myc mRNA stability, resulting in a higher accumulation of the c-Myc proteins.

  17. c-myc gene sequences and the phylogeny of bats and other eutherian mammals.

    Science.gov (United States)

    Miyamoto, M M; Porter, C A; Goodman, M

    2000-09-01

    The complete protein-coding sequences of the c-myc proto-oncogene were determined for five species of four new orders of eutherian (placental) mammals. These newly obtained sequences were aligned to each other and to other available orthologs for the phylogenetic estimation of eutherian interordinal relationships. Several measures of sequence difference and base composition were first calculated to assess the major evolutionary properties of the three codon positions and two protein-coding exons of the gene. On the basis of these calculations, different parsimony, distance, and maximum likelihood approaches were adopted, with the most sophisticated involving the separate, then combined, likelihood analyses of the third codon positions of exon 2 versus all other sites. These phylogenetic approaches provided clear support for the grouping of Chiroptera (bats) with Artiodactyla (ruminants, camels, and pigs) and Carnivora (cats, dogs, and their allies), an interordinal arrangement that receives strong corroboration from other lines of evidence including complete mitochondrial DNA sequences. In contrast, these analyses failed to provide strong to reasonable support for any other interordinal group. This study concludes with specific recommendations about sampling and other strategies for maximizing the phylogenetic contributions of the c-myc gene to the continued resolution of the eutherian ordinal tree. PMID:12116424

  18. Depressive Effect of the Antisense Oligonucleotides of C-myc and PCNA on the Proliferation of VSMC

    Institute of Scientific and Technical Information of China (English)

    Qingxian Li; Yanfu Wang; Yuhua Liao; Huiling Zhang; Yanying Jiang

    2007-01-01

    To study the depressive effect of the antisense oligonuceotides (ASODN) of c-myc and proliferating cell nuclear antigen (PCNA) on the proliferation of VSMC.Methods Taking the VSMC obtained from rat aorta thoracalis cultured 4 ~ 8 generation as research object.The objects were divided into three groups to carry out control study:control group,PCNA ASODN group and c-myc ASODN group.The ASODNs' working concentration all were 1:50.The depressive effect of ASODN on VSMC proliferation was investigated by cell counting,MTT and 3H-TdR incorporation assay;PCNA and c-myc expression were detected by immunohistochemical method after transferring PCNA successfully;the corresponding gene was inhibited obviously;compared with control group ( P < 0.05 ).Conclusions PCNA and c-myc might play a considerable role in the VSMC proliferation process.The corresponding gene could be depressed successfully after transferring PCNA and c-myc ASODN into VSMC,and then the proliferation of VSMC was slowed down.This study presented a beneficial proposal and theoretical fundament for atherosclerotic treatment.

  19. C-Myc regulation by costimulatory signals modulates the generation of CD8+ memory T cells during viral infection.

    Science.gov (United States)

    Haque, Mohammad; Song, Jianyong; Fino, Kristin; Wang, Youfei; Sandhu, Praneet; Song, Xinmeng; Norbury, Christopher; Ni, Bing; Fang, Deyu; Salek-Ardakani, Shahram; Song, Jianxun

    2016-01-01

    The signalling mechanisms of costimulation in the development of memory T cells remain to be clarified. Here, we show that the transcription factor c-Myc in CD8(+) T cells is controlled by costimulatory molecules, which modulates the development of memory CD8(+) T cells. C-Myc expression was dramatically reduced in Cd28(-/-) or Ox40(-/-) memory CD8(+) T cells, and c-Myc over-expression substantially reversed the defects in the development of T-cell memory following viral infection. C-Myc regulated the expression of survivin, an inhibitor of apoptosis, which promoted the generation of virus-specific memory CD8(+) T cells. Moreover, over-expression of survivin with bcl-xL, a downstream molecule of NF-κB and intracellular target of costimulation that controls survival, in Cd28(-/-) or Ox40(-/-) CD8(+) T cells, reversed the defects in the generation of memory T cells in response to viral infection. These results identify c-Myc as a key controller of memory CD8(+) T cells from costimulatory signals.

  20. C-Myc regulation by costimulatory signals modulates the generation of CD8+ memory T cells during viral infection.

    Science.gov (United States)

    Haque, Mohammad; Song, Jianyong; Fino, Kristin; Wang, Youfei; Sandhu, Praneet; Song, Xinmeng; Norbury, Christopher; Ni, Bing; Fang, Deyu; Salek-Ardakani, Shahram; Song, Jianxun

    2016-01-01

    The signalling mechanisms of costimulation in the development of memory T cells remain to be clarified. Here, we show that the transcription factor c-Myc in CD8(+) T cells is controlled by costimulatory molecules, which modulates the development of memory CD8(+) T cells. C-Myc expression was dramatically reduced in Cd28(-/-) or Ox40(-/-) memory CD8(+) T cells, and c-Myc over-expression substantially reversed the defects in the development of T-cell memory following viral infection. C-Myc regulated the expression of survivin, an inhibitor of apoptosis, which promoted the generation of virus-specific memory CD8(+) T cells. Moreover, over-expression of survivin with bcl-xL, a downstream molecule of NF-κB and intracellular target of costimulation that controls survival, in Cd28(-/-) or Ox40(-/-) CD8(+) T cells, reversed the defects in the generation of memory T cells in response to viral infection. These results identify c-Myc as a key controller of memory CD8(+) T cells from costimulatory signals. PMID:26791245

  1. Abnormal expression of c-Myc in human bronchial epithelial cells malignantly transformed by anti-BPDE

    Institute of Scientific and Technical Information of China (English)

    Juan FU; Yiguo JIANG; Xuemin CHEN

    2008-01-01

    Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) is a metabolite of benzo[a]pyrene (B[a] P) and acts as a potent mutagen in mammalian systems. However, molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood. Here, we investigated the expression of proto-oncogene c-myc in human bronchial epithelial cells (16H BE-T) transformed by exposure to anti-BPDE. The levels ofmRNA and pro-tein of c-M yc were examined in the 16HBE-T and vehicle-treated control cells (16HBE-N) by using different meth-ods respectively, including reverse transcriptase-polymer-ase chain reaction (RT-PCR), quantitative real-time PCR (Q-PCR), western blot and immunocytochemical meth-ods. The level of c-myc mRNA appeared to be signifi-cantly increased in 16HBE-T, as compared with those of the 16H BE-N. Likewise, the expression of c-Myc protein was significantly enhanced as compared with those of the control cells. Moreover, the localization of c-Myc protein shows mainly nuclear staining in 16HBE-T. In conclu-sion, the abnormal expression of c-Myc was present in anti-BPDE malignantly transformed 16HBE cells, which may be involved in the carcinogenesis molecular mech-anism of anti-BPDE.

  2. Effect of c-myc on the ultrastructural structure of cochleae in guinea pigs with noise induced hearing loss

    Energy Technology Data Exchange (ETDEWEB)

    Han, Yu; Zhong, Cuiping [Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 Shaanxi Province (China); Hong, Liu [First Division of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 Shaanxi Province (China); Wang, Ye; Qiao, Li [Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 Shaanxi Province (China); Qiu, Jianhua, E-mail: qiujh@fmmu.edu.cn [Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 Shaanxi Province (China)

    2009-12-18

    Noise over-stimulation may induce hair cells loss and hearing deficit. The c-myc oncogene is a major regulator for cell proliferation, growth, and apoptosis. However, the role of this gene in the mammalian cochlea is still unclear. The study was designed to firstly investigate its function under noise condition, from the aspect of cochlear ultrastructural changes. We had established the adenoviral vector of c-myc gene and delivered the adenovirus suspension into the scala tympani of guinea pigs 4 days before noise exposure. The empty adenoviral vectors were injected as control. Then, all subjects were exposed to 4-kHz octave-band noise at 110 dB SPL for 8 h/day, 3 days consecutively. Auditory thresholds were assessed by auditory brainstem response, prior to and 7 days following noise exposure. On the seventh days after noise exposure, the cochlear sensory epithelia surface was observed microscopically and the cochleae were taken to study the ultrastructural changes. The results indicated that auditory threshold shift after noise exposure was higher in the ears treated with Ad.EGFP than that treated with Ad.c-myc-EGFP. Stereocilia loss and the disarrangement of outer hair cells were observed, with greater changes found in the Ad.EGFP group. Also, the ultrastructure changes were severe in the Ad.EGFP group, but not obvious in the Ad.c-myc-EGFP group. Therefore, c-myc gene might play an unexpected role in hearing functional and morphological protection from acoustic trauma.

  3. Transient in utero knockout (TIUKO of C-MYC affects late lung and intestinal development in the mouse

    Directory of Open Access Journals (Sweden)

    Zhou Pengbo

    2004-04-01

    Full Text Available Abstract Background Developmentally important genes often result in early lethality in knockout animals. Thus, the direct role of genes in late gestation organogenesis cannot be assessed directly. In utero delivery of transgenes was shown previously to result in high efficiency transfer to pulmonary and intestinal epithelial stem cells. Thus, this technology can be used to evaluate late gestation development. Results In utero gene transfer was used to transfer adenovirus with either an antisense c-myc or a C-MYC ubiquitin targeting protein to knockout out c-myc expression in late gestation lung and intestines. Using either antisense or ubiquitin mediated knockout of C-MYC levels in late gestation resulted in similar effects. Decreased complexity was observed in both intestines and lungs. Stunted growth of villi was evident in the intestines. In the lung, hypoplastic lungs with disrupted aveolarization were observed. Conclusions These data demonstrated that C-MYC was required for cell expansion and complexity in late gestation lung and intestinal development. In addition they demonstrate that transient in utero knockout of proteins may be used to determine the role of developmentally important genes in the lungs and intestines.

  4. Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8

    OpenAIRE

    Zhigang Li; Lixue Dong; Eric Dean; Yang, Li V.

    2013-01-01

    Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65) is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partia...

  5. Acidosis decreases c-Myc oncogene expression in human lymphoma cells: a role for the proton-sensing G protein-coupled receptor TDAG8.

    Science.gov (United States)

    Li, Zhigang; Dong, Lixue; Dean, Eric; Yang, Li V

    2013-01-01

    Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65) is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partially rescues c-Myc expression, respectively. Acidic pH alone is insufficient to reduce c-Myc expression, as it does not decrease c-Myc in H1299 lung cancer cells expressing very low levels of pH-sensing G protein-coupled receptors (GPCRs). Instead, c-Myc is slightly increased by acidosis in H1299 cells, but this increase is completely inhibited by ectopic overexpression of TDAG8. Interestingly, TDAG8 expression is decreased by more than 50% in human lymphoma samples in comparison to non-tumorous lymph nodes and spleens, suggesting a potential tumor suppressor function of TDAG8 in lymphoma. Collectively, our results identify a novel mechanism of c-Myc regulation by acidosis in the tumor microenvironment and indicate that modulation of TDAG8 and related pH-sensing receptor pathways may be exploited as a new approach to inhibit Myc expression. PMID:24152439

  6. Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8

    Directory of Open Access Journals (Sweden)

    Zhigang Li

    2013-10-01

    Full Text Available Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65 is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partially rescues c-Myc expression, respectively. Acidic pH alone is insufficient to reduce c-Myc expression, as it does not decrease c-Myc in H1299 lung cancer cells expressing very low levels of pH-sensing G protein-coupled receptors (GPCRs. Instead, c-Myc is slightly increased by acidosis in H1299 cells, but this increase is completely inhibited by ectopic overexpression of TDAG8. Interestingly, TDAG8 expression is decreased by more than 50% in human lymphoma samples in comparison to non-tumorous lymph nodes and spleens, suggesting a potential tumor suppressor function of TDAG8 in lymphoma. Collectively, our results identify a novel mechanism of c-Myc regulation by acidosis in the tumor microenvironment and indicate that modulation of TDAG8 and related pH-sensing receptor pathways may be exploited as a new approach to inhibit Myc expression.

  7. Specific regulation of mRNA cap methylation by the c-Myc and E2F1 transcription factors

    Science.gov (United States)

    Cole, Michael D.; Cowling, Victoria H.

    2009-01-01

    Methylation of the mRNA 5′ guanosine cap is essential for efficient gene expression. The 5′methyl cap binds to eIF4E, which is the first step in the recruitment of mRNA to the 40S ribosomal subunit. To investigate whether mRNA cap methylation is regulated in a gene-specific manner, we established a method to detect the relative level of cap methylation on specific mRNAs. We found that two transcription factors, c-Myc and E2F1, induce cap methylation of their transcriptional target genes, and therefore, c-Myc and E2F1 upregulate gene expression by simultaneously inducing transcription and promoting translation. c-Myc-induced cap methylation is greater than transcriptional induction for the majority of its target genes, indicating that this is a major mechanism by which Myc regulates gene expression. PMID:19137018

  8. AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-MYC dephosphorylation and degradation

    Science.gov (United States)

    Cianfanelli, Valentina; Fuoco, Claudia; Lorente, Mar; Salazar, Maria; Quondamatteo, Fabio; Gherardini, Pier Federico; De Zio, Daniela; Nazio, Francesca; Antonioli, Manuela; D’Orazio, Melania; Skobo, Tatjana; Bordi, Matteo; Rohde, Mikkel; Dalla Valle, Luisa; Helmer-Citterich, Manuela; Gretzmeier, Christine; Dengjel, Joern; Fimia, Gian Maria; Piacentini, Mauro; Di Bartolomeo, Sabrina; Velasco, Guillermo; Cecconi, Francesco

    2016-01-01

    Inhibition of a main regulator of cell metabolism, the protein kinase mTOR, induces autophagy and inhibits cell proliferation. However, the molecular pathways involved in the cross-talk between these two mTOR-dependent cell processes are largely unknown. Here we show that the scaffold protein AMBRA1, a member of the autophagy signalling network and a downstream target of mTOR, regulates cell proliferation by facilitating the dephosphorylation and degradation of the proto-oncogene C-MYC. We found that AMBRA1 favors the interaction between C-MYC and its phosphatase PP2A and that, when mTOR is inhibited, it enhances PP2A activity on this specific target, thereby reducing the cell division rate. As expected, such a de-regulation of C-MYC correlates with increased tumorigenesis in AMBRA1-defective systems, thus supporting a role for AMBRA1 as a haploinsufficient tumour suppressor gene. PMID:25438055

  9. Bombesin stimulation of c-fos and c-myc gene expression in cultured of Swiss 3T3 cells

    International Nuclear Information System (INIS)

    Bombesin has been show to be a potent mitogen for Swiss 3T3 cells. At nanomolar concentrations it stimulates DNA synthesis in quiescent cultures of 3T3 cells and also induces the expression of c-fos and c-myc mRNA. c-fos mRNA transcripts dramatically increase 15 min after the addition of bombesin, are still abundant after 30-60 min and then decrease. c-myc mRNA induction is detectable later, 1 h after bombesin treatment. Conversely, no changes in c-Ki-ras expression are observed after stimulation with bombesin. These results demonstrate that the increased expression of c-fos and c-myc mRNAs appears to be a common response to diverse agents that induce DNA synthesis and cell proliferation

  10. EFFECT OF STENT ABSORBED c-myc ANTISENSE OLIGODEOXYNUCLEOTIDE ON SMOOTH MUSCLE CELLS APOPTOSIS IN RABBIT CAROTID ARTERY

    Institute of Scientific and Technical Information of China (English)

    张新霞; 崔长琮; 李江; 崔翰斌; 徐仓宝; 朱参战

    2002-01-01

    Objective To investigate the effect of gelatin coated Platinium-Iridium stent absorbed c-myc antisense oligodeoxynucleotide (ASODN) on smooth muscle cells apoptosis in a normal rabbit carotid arteries. Methods Gelatin coated Platinium-Iridium stents were implanted in the right carotid arteries of 32 rabbits under vision. Animals were randomly divided into control group and treated group receiving c-myc ASODN (n=16, respectively). On 7, 14, 30 and 90 days following the stenting procedure ,morphometry for caculation of neointimal area and mean neointimal thickness were performed.The expression of c-myc protein was detected by immunohistochemical method. Apoptotic smooth muscle cells was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL). Results At 7 and 14 days after stenting,there were no detectable apoptotic cells in both groups. The apoptotic cells occurred in the neointima 30 and 90 days after stenting, and the number of apoptotic cells at 30 days were less [4.50±1.29 vs 25.75±1.89 (number/0.1mm2)] than that at 90 days [13.50±1.91 vs 41.50±6.46 (number/0.1mm2)]. Meanwhile c-myc ASODN induced more apoptotic cells than the control group(P<0.0001). c-myc protein expression was weak positive or negative in treated group and positive in control group.Conclusion c-myc ASODN can induce smooth muscle cells apoptosis after stenting in normal rabbit carotid arteries,and it can be used to prevent in-stent restenosis.

  11. Thermal injuries induce gene expression of endogenous c-fos, c-myc and bFGF in burned tissues

    Institute of Scientific and Technical Information of China (English)

    付小兵; 顾小曼; 孙同柱; 杨银辉; 孙晓庆; 盛志勇

    2003-01-01

    Objective To investigate the expression sequence and distribution characteristics of the protooncogenes c-fos, c-myc and endogenous basic fibroblast growth factor (bFGF ) genes in burned tissues, and to explore the possible effects of changes in the se genes' functions on wound healing. Methods Partial-thickness burns of 30% TBSA were established on backs of Wistar rats. Insitu hybridization and histological methods were used to detect expression of c-fos, c-myc and bFGF genes in normal and burned tissue at 3 h, 6 h, 1 d, 3 d , 7 d and 14 d postburn. Results Although expression of c-fos and c-myc genes and bFGF gene could be found in normal skin, the expression of all three were markedly induced by burn wounds and the expression models in sequence and distribution were quite different. Expre ssion of c-fos gene increased and peaked at 6 h. Signals were mainly localiz ed in both nuclei of dermal fibroblasts and monocytes. The expression of bFGF gene increased at 6 h and peaked at 1 d postburn, and was distributed in the cyt oplasm of fibroblasts. C-myc gene peaked 3 d postburn and was also distributed in the cytoplasm of fibroblasts. Conclusions These results indicated that thermal injury could induce the expression of c-fos, c-myc and bFGF at gene level, showing phasic control and regional distributi on. The phasic expression of these genes suggests that there is an interaction between protooncogenes and bFGF, which may play an important role in wound heali ng. The different expressions of c-fos and c-myc play an inducing role in reg ulating bFGF, and in turn affect wound healing.

  12. Elevation of c-MYC disrupts HLA class II-mediated immune recognition of human B cell tumors.

    Science.gov (United States)

    God, Jason M; Cameron, Christine; Figueroa, Janette; Amria, Shereen; Hossain, Azim; Kempkes, Bettina; Bornkamm, Georg W; Stuart, Robert K; Blum, Janice S; Haque, Azizul

    2015-02-15

    Elevated levels of the transcription factor c-myc are strongly associated with various cancers, and in particular B cell lymphomas. Although many of c-MYC's functions have been elucidated, its effect on the presentation of Ag through the HLA class II pathway has not been reported previously. This is an issue of considerable importance, given the low immunogenicity of many c-MYC-positive tumors. We report in this paper that increased c-MYC expression has a negative effect on the ability of B cell lymphomas to functionally present Ags/peptides to CD4(+) T cells. This defect was associated with alterations in the expression of distinct cofactors as well as interactions of antigenic peptides with class II molecules required for the presentation of class II-peptide complexes and T cell engagement. Using early passage Burkitt's lymphoma (BL) tumors and transformed cells, we show that compared with B lymphoblasts, BL cells express decreased levels of the class II editor HLA-DM, lysosomal thiol-reductase GILT, and a 47-kDa enolase-like protein. Functional Ag presentation was partially restored in BL cells treated with a c-MYC inhibitor, demonstrating the impact of this oncogene on Ag recognition. This restoration of HLA class II-mediated Ag presentation in early passage BL tumors/cells was linked to enhanced HLA-DM expression and a concurrent decrease in HLA-DO in BL cells. Taken together, these results reveal c-MYC exerts suppressive effects at several critical checkpoints in Ag presentation, which contribute to the immunoevasive properties of BL tumors.

  13. Cancer-associated fibroblasts promote endometrial cancer growth via activation of interleukin-6/STAT-3/c-Myc pathway.

    Science.gov (United States)

    Subramaniam, Kavita S; Omar, Intan Sofia; Kwong, Soke Chee; Mohamed, Zahurin; Woo, Yin Ling; Mat Adenan, Noor Azmi; Chung, Ivy

    2016-01-01

    Cancer-associated fibroblasts (CAFs) secrete various pro-tumorigenic cytokines, yet the role of these cytokines in the progression of endometrial cancer remains unclear. We found that CAFs isolated from human endometrial cancer (EC) tissues secreted high levels of interleukin-6 (IL-6), which promotes EC cell proliferation in vitro. Neutralizing IL-6 in CAF-conditioned media reduced (47% inhibition) while IL-6 recombinant protein increased cell proliferation (~2.4 fold) of both EC cell lines and primary cultures. IL-6 receptors (IL-6R and gp130) were expressed only in EC epithelial cells but not in CAF, indicating a one-way paracrine signaling. In the presence of CAF-conditioned media, Janus kinase/signal transducers and activators of transcription (JAK/STAT3) pathway was activated in EC cells. Treatment with JAK and STAT3 specific inhibitors, AD412 and STATTIC, respectively, significantly abrogated CAF-mediated cell proliferation, indicating the role of IL-6 activation in EC cell proliferation. We further showed that one of STAT-3 target genes, c-Myc, was highly induced in EC cells after exposure to CAF-conditioned medium at both mRNA (>105-fold vs. control) and protein level (>2-fold vs. control). EC cell proliferation was dependent on c-Myc expression, as RNAi-mediated c-Myc down-regulation led to a significant 46% reduction in cell viability when compared with scrambled control. Interestingly, CAF-conditioned media failed to promote proliferation in EC cells with reduced c-Myc expression, suggesting that CAF-mediated cell proliferation was also dependent on c-Myc expression. Subcutaneous tumor xenograft model showed that EC cells grew at least 1.4 times larger when co-injected with CAF, when compared to those injected with EC cells alone. Mice injected with EC cells with down-regulated c-Myc expression, however, showed at least 2.5 times smaller tumor compared to those in control group. Notably, there was no increase of tumor size when co-injected with CAFs

  14. Long-range oncogenic activation of Igh-c-myc translocations by the Igh 3' regulatory region.

    Science.gov (United States)

    Gostissa, Monica; Yan, Catherine T; Bianco, Julia M; Cogné, Michel; Pinaud, Eric; Alt, Frederick W

    2009-12-10

    B-cell malignancies, such as human Burkitt's lymphoma, often contain translocations that link c-myc or other proto-oncogenes to the immunoglobulin heavy chain locus (IgH, encoded by Igh). The nature of elements that activate oncogenes within such translocations has been a long-standing question. Translocations within Igh involve DNA double-strand breaks initiated either by the RAG1/2 endonuclease during variable, diversity and joining gene segment (V(D)J) recombination, or by activation-induced cytidine deaminase (AID, also known as AICDA) during class switch recombination (CSR). V(D)J recombination in progenitor B (pro-B) cells assembles Igh variable region exons upstream of mu constant region (Cmu) exons, which are the first of several sets of C(H) exons ('C(H) genes') within a C(H) locus that span several hundred kilobases (kb). In mature B cells, CSR deletes Cmu and replaces it with a downstream C(H) gene. An intronic enhancer (iEmu) between the variable region exons and Cmu promotes V(D)J recombination in developing B cells. Furthermore, the Igh 3' regulatory region (Igh3'RR) lies downstream of the C(H) locus and modulates CSR by long-range transcriptional enhancement of C(H) genes. Transgenic mice bearing iEmu or Igh3'RR sequences fused to c-myc are predisposed to B lymphomas, demonstrating that such elements can confer oncogenic c-myc expression. However, in many B-cell lymphomas, Igh-c-myc translocations delete iEmu and place c-myc up to 200 kb upstream of the Igh3'RR. Here we address the oncogenic role of the Igh3'RR by inactivating it in two distinct mouse models for B-cell lymphoma with Igh-c-myc translocations. We show that the Igh3'RR is dispensable for pro-B-cell lymphomas with V(D)J recombination-initiated translocations, but is required for peripheral B-cell lymphomas with CSR-associated translocations. As the Igh3'RR is not required for CSR-associated Igh breaks or Igh-c-myc translocations in peripheral B-cell lymphoma progenitors, we conclude that

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

    Directory of Open Access Journals (Sweden)

    Trumpp Andreas

    2009-09-01

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

  16. USP10 Antagonizes c-Myc Transcriptional Activation through SIRT6 Stabilization to Suppress Tumor Formation

    Directory of Open Access Journals (Sweden)

    Zhenghong Lin

    2013-12-01

    Full Text Available The reduced protein expression of SIRT6 tumor suppressor is involved in tumorigenesis. The molecular mechanisms underlying SIRT6 protein downregulation in human cancers remain unknown. Using a proteomic approach, we have identified the ubiquitin-specific peptidase USP10, another tumor suppressor, as one of the SIRT6-interacting proteins. USP10 suppresses SIRT6 ubiquitination to protect SIRT6 from proteasomal degradation. USP10 antagonizes the transcriptional activity of the c-Myc oncogene through SIRT6, as well as p53, to inhibit cell-cycle progression, cancer cell growth, and tumor formation. To support this conclusion, we detected significant reductions in both USP10 and SIRT6 protein expression in human colon cancers. Our study discovered crosstalk between two tumor-suppressive genes in regulating cell-cycle progression and proliferation and showed that dysregulated USP10 function promotes tumorigenesis through SIRT6 degradation.

  17. Effects of an inducible anti-sense c-myc gene transfer in a drug-resistant human small-cell-lung-carcinoma cell line

    NARCIS (Netherlands)

    Van Waardenburg, R C; Meijer, C; Burger, H; Nooter, K; De Vries, E G; Mulder, N H; de Jong, Steven

    1997-01-01

    Small-cell-lung-cancer (SCLC) is characterized by rapid development of resistance to cytotoxic agents, such as cisplatin (cDDP) and anthracyclines. c-myc over-expression is one of the reported genetic alterations in this tumor. Amplification of the c-myc gene in this and other cancers is often corre

  18. XPC Promotes Pluripotency of Human Dental Pulp Cells through Regulation of Oct-4/Sox2/c-Myc.

    Science.gov (United States)

    Liu, Lu; Peng, Zhengjun; Xu, Zhezhen; Wei, Xi

    2016-01-01

    Introduction. Xeroderma pigmentosum group C (XPC), essential component of multisubunit stem cell coactivator complex (SCC), functions as the critical factor modulating pluripotency and genome integrity through interaction with Oct-4/Sox2. However, its specific role in regulating pluripotency and multilineage differentiation of human dental pulp cells (DPCs) remains unknown. Methods. To elucidate the functional role XPC played in pluripotency and multilineage differentiation of DPCs, expressions of XPC in DPCs with long-term culture were examined by real-time PCR and western blot. DPCs were transfected with lentiviral-mediated human XPC gene; then transfection rate was investigated by real-time PCR and western blot. Cell cycle, apoptosis, proliferation, senescence, multilineage differentiation, and expression of Oct-4/Sox2/c-Myc in transfected DPCs were examined. Results. XPC, Oct-4, Sox2, and c-Myc were downregulated at P7 compared with P3 in DPCs with long-term culture. XPC genes were upregulated in DPCs at P2 after transfection and maintained high expression level at P3 and P7. Cell proliferation, PI value, and telomerase activity were enhanced, whereas apoptosis was suppressed in transfected DPCs. Oct-4/Sox2/c-Myc were significantly upregulated, and multilineage differentiation in DPCs with XPC overexpression was enhanced after transfection. Conclusions. XPC plays an essential role in the modulation of pluripotency and multilineage differentiation of DPCs through regulation of Oct-4/Sox2/c-Myc. PMID:27127517

  19. XPC Promotes Pluripotency of Human Dental Pulp Cells through Regulation of Oct-4/Sox2/c-Myc

    Directory of Open Access Journals (Sweden)

    Lu Liu

    2016-01-01

    Full Text Available Introduction. Xeroderma pigmentosum group C (XPC, essential component of multisubunit stem cell coactivator complex (SCC, functions as the critical factor modulating pluripotency and genome integrity through interaction with Oct-4/Sox2. However, its specific role in regulating pluripotency and multilineage differentiation of human dental pulp cells (DPCs remains unknown. Methods. To elucidate the functional role XPC played in pluripotency and multilineage differentiation of DPCs, expressions of XPC in DPCs with long-term culture were examined by real-time PCR and western blot. DPCs were transfected with lentiviral-mediated human XPC gene; then transfection rate was investigated by real-time PCR and western blot. Cell cycle, apoptosis, proliferation, senescence, multilineage differentiation, and expression of Oct-4/Sox2/c-Myc in transfected DPCs were examined. Results. XPC, Oct-4, Sox2, and c-Myc were downregulated at P7 compared with P3 in DPCs with long-term culture. XPC genes were upregulated in DPCs at P2 after transfection and maintained high expression level at P3 and P7. Cell proliferation, PI value, and telomerase activity were enhanced, whereas apoptosis was suppressed in transfected DPCs. Oct-4/Sox2/c-Myc were significantly upregulated, and multilineage differentiation in DPCs with XPC overexpression was enhanced after transfection. Conclusions. XPC plays an essential role in the modulation of pluripotency and multilineage differentiation of DPCs through regulation of Oct-4/Sox2/c-Myc.

  20. Effect of hammerhead ribozyme that specifically cleaves c-myc mRNA on proliferation of vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    栾荣华; 贾国良; 李伟; 贾战生; 连建奇

    2003-01-01

    Ojective: To investigate the effect of hammerhead ribozyme that specifically cleaves c-myc mRNA on the proliferation of vascular smooth muscle cells (VSMCs). Methods: Based on the computer analysis of the secondary structure of c-myc mRNA, nt 2029 in rat c-myc oncogene was selected as a cleaving site for hammerhead ribozyme and the ribozyme was designed. With automatic DNA synthesizer, the two complementary DNA strands of the ribozyme were synthesized. The ribozyme gene was cloned into pGEM3Zf (+) vector and subcloned into eukaryotic expression pcDNA3 vector. The recombinant pcDNA-Rz was transfected into the cultured rat VSMCs by lipofectAMINE mediated DNA transfection protocol and individual cell clones were selected by G418. Results: The sequence of ribozyme gene inserted in pGEM3Zf (+) vector was proved to be perfectly correct. In VSMCs transfected with recombinant pcDNA-Rz, flow cytometry analysis showed that the S phase and G2/M fractions were decreased significantly and cell proliferation stagnated in the G0/G1 phase. Conclusion: The results suggest that hammerhead ribozyme that specifically cleaves c-myc mRNA can significantly inhibit the proliferation of VSMCs.

  1. c-Myc Enhances Sonic Hedgehog-Induced Medulloblastoma Formation from Nestin-Expressing Neural Progenitors in Mice

    Directory of Open Access Journals (Sweden)

    Ganesh Rao

    2003-05-01

    Full Text Available Medulloblastomas are malignant brain tumors that arise in the cerebella of children. The presumed cellsof-origin are undifferentiated precursors of granule neurons that occupy the external granule layer (EGL of the developing cerebellum. The overexpression of proteins that normally stimulate proliferation of neural progenitor cells may initiate medulloblastoma formation. Two known mitogens for neural progenitors are the c-Myc oncoprotein and Sonic hedgehog (Shh, a crucial determinant of embryonic pattern formation in the central nervous system. We modeled the ability of c-Myc and Shh to induce medulloblastoma in mice using the RCAS/tv-a system, which allows postnatal gene transfer and expression in a cell type-specific manner. We targeted the expression of Shh and c-Myc to nestin-expressing neural progenitor cells by injecting replication-competent ALV splice acceptor (RCAS vectors into the cerebella of newborn mice. Following injection with RCAS-Shh alone, 3/32 (9% mice developed medulloblastomas and 5/32 showed multifocal hyperproliferation of the EGL, possibly a precursor stage of medulloblastoma. Following injection with RCAS-Shh plus RCAS-Myc, 9/39 (23% mice developed medulloblastomas. We conclude that nestin-expressing neural progenitors, present in the cerebellum at birth, can act as the cells-of-origin for medulloblastoma, and that c-Myc cooperates with Shh to enhance tumorigenicity.

  2. Alterations of C-MYC, NKX3.1, and E-cadherin expression in canine prostate carcinogenesis

    DEFF Research Database (Denmark)

    Fonseca-Alves, Carlos E; Rodrigues, Marcela M P; de Moura, Veridiana M B D;

    2013-01-01

    therapies. In humans, the PCa frequently exhibits mutations in the C-MYC and a reduced expression of the E-cadherin and NKX3.1 proteins. This study's objective was to evaluate the NKX3.1, C-MYC, and E-cadherin expression in the canine normal prostate, benign prostatic hyperplasia (BPH), proliferative...... inflammatory atrophy (PIA) and PCa and to verify differences in expression and subcellular localization of these proteins in the prostatic carcinogenesis. A tissue microarray (TMA) slide was constructed, and immunohistochemistry with antibodies raised against C-MYC, NKX3.1, E-cadherin and p63 was performed...... using the peroxidase and DAB methods. The C-MYC protein expression was elevated in the cytoplasm and nuclei of the canine PCa and PIA compared with the normal prostate (P = 0.004. The NKX3.1 protein expression was reduced in 94.75% of the PCa and 100% of the PIA compared with the normal prostate (P = 0...

  3. Telomerase in relation to expression of p53, c-Myc and estrogen receptor in ovarian tumours

    NARCIS (Netherlands)

    Wisman, GBA; Hollema, H; Helder, MN; Knol, AJ; Van Der Meer, GT; Krans, M; De Jong, S; De Vries, EGE; Van Der Zee, AGJ

    2003-01-01

    Telomerase activity and its subunits (hTERC, hTERT mRNA) were evaluated in ovarian tumours in relation to the expression of p53, c-Myc and estrogen receptor (ER). Furthermore, relations between telomerase activity, hTERC and hTERT with known clinicopathologic prognostic factors and survival in patie

  4. c-Myc regulates proliferation and Fgf10 expression in airway smooth muscle after airway epithelial injury in mouse.

    Science.gov (United States)

    Volckaert, Thomas; Campbell, Alice; De Langhe, Stijn

    2013-01-01

    During lung development, Fibroblast growth factor 10 (Fgf10), which is expressed in the distal mesenchyme and regulated by Wnt signaling, acts on the distal epithelial progenitors to maintain them and prevent them from differentiating into proximal (airway) epithelial cells. Fgf10-expressing cells in the distal mesenchyme are progenitors for parabronchial smooth muscle cells (PSMCs). After naphthalene, ozone or bleomycin-induced airway epithelial injury, surviving epithelial cells secrete Wnt7b which then activates the PSMC niche to induce Fgf10 expression. This Fgf10 secreted by the niche then acts on a subset of Clara stem cells to break quiescence, induce proliferation and initiate epithelial repair. Here we show that conditional deletion of the Wnt target gene c-Myc from the lung mesenchyme during development does not affect proper epithelial or mesenchymal differentiation. However, in the adult lung we show that after naphthalene-mediated airway epithelial injury c-Myc is important for the activation of the PSMC niche and as such induces proliferation and Fgf10 expression in PSMCs. Our data indicate that conditional deletion of c-Myc from PSMCs inhibits airway epithelial repair, whereas c-Myc ablation from Clara cells has no effect on airway epithelial regeneration. These findings may have important implications for understanding the misregulation of lung repair in asthma and COPD. PMID:23967208

  5. Induction of endogenous telomerase (hTERT) by c-Myc in WI-38 fibroblasts transformed with specific genetic elements.

    Science.gov (United States)

    Casillas, Mark A; Brotherton, Scott L; Andrews, Lucy G; Ruppert, J Michael; Tollefsbol, Trygve O

    2003-10-16

    Elucidation of the mechanisms governing expression of the human telomerase reverse transcriptase (hTERT) is important for understanding cancer pathogenesis. Approximately 90% of tumors express hTERT, the major catalytic component of telomerase. Activation of telomerase is an early event, and high levels of this activity correlate with poor prognosis. Recent studies have shown that the transcription factors c-Myc and Mad1 activate and repress hTERT, respectively. It is not clear how these transcription factors compete for the same recognition sequence in the hTERT core promoter region. Studies have shown that the combined expression of SV40 large T antigen (T-Ag), hTERT, and H-Ras is able to transform human cells. In this study, we used a distinct human cell type, WI-38 fetal lung fibroblasts used extensively for senescence studies. We transduced cells with amphotropic retroviral constructs containing SV40 T antigen, hTERT, and activated H-ras. Transduced cells exhibited anchorage independence in soft agar and expressed increased levels of c-Myc and endogenous hTERT. These effects were observed by 25 population doublings (PDs) following the establishment of the neoplastic cell line. During the process of transformation, we observed a switch from Mad1/Max to c-Myc/Max binding to oligonucleotide sequences containing the hTERT promoter distal and proximal E-boxes. c-Myc can bind specifically to the hTERT promoter in vitro, indicating that c-Myc expression in tumors may account for the increased expression of hTERT observed in vivo. These findings indicate that the widely used model system of WI-38 fibroblasts can be employed for transformation studies using defined genetic elements and that the endogenous hTERT and c-Myc are induced in these cells during early tumorigenesis. Such studies should have important implications in the mechanisms of hTERT and c-Myc induction in the beginning stages of tumorigenesis and facilitate extension of these studies to novel models of

  6. Modification of the Tumor Microenvironment in KRAS or c-MYC-Induced Ovarian Cancer-Associated Peritonitis

    Science.gov (United States)

    Kawana, Kei; Adachi, Katsuyuki; Kawata, Akira; Ogishima, Juri; Nakamura, Hiroe; Fujimoto, Asaha; Sato, Masakazu; Inoue, Tomoko; Nishida, Haruka; Furuya, Hitomi; Tomio, Kensuke; Arimoto, Takahide; Koga, Kaori; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Kiyono, Tohru; Osuga, Yutaka; Fujii, Tomoyuki

    2016-01-01

    The most common properties of oncogenes are cell proliferation and the prevention of apoptosis in malignant cells, which, as a consequence, induce tumor formation and dissemination. However, the effects of oncogenes on the tumor microenvironment (TME) have not yet been examined in detail. The accumulation of ascites accompanied by chronic inflammation and elevated concentrations of VEGF is a hallmark of the progression of ovarian cancer. We herein demonstrated the mechanisms by which oncogenes contribute to modulating the ovarian cancer microenvironment. c-MYC and KRAS were transduced into the mouse ovarian cancer cell line ID8. ID8, ID8-c-MYC, or ID8-KRAS cells were then injected into the peritoneal cavities of C57/BL6 mice and the production of ascites was assessed. ID8-c-MYC and ID8-KRAS both markedly accelerated ovarian cancer progression in vivo, whereas no significant differences were observed in proliferative activity in vitro. ID8-KRAS in particular induced the production of ascites, which accumulated between approximately two to three weeks after the injection, more rapidly than ID8 and ID8-c-MYC (between nine and ten weeks and between six and seven weeks, respectively). VEGF concentrations in ascites significantly increased in c-MYC-induced ovarian cancer, whereas the concentrations of inflammatory cytokines in ascites were significantly high in KRAS-induced ovarian cancer and were accompanied by an increased number of neutrophils in ascites. A cytokine array revealed that KRAS markedly induced the expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in ID8 cells. These results suggest that oncogenes promote cancer progression by modulating the TME in favor of cancer progression. PMID:27483433

  7. Tissue array for Tp53, C-myc, CCND1 gene over-expression in different tumors

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To rapidly detect molecular alterations in different malignancies and investigate the possible role of Tp53, C-myc, and CCND1 genes in development of tumors in human organs and their adjacent normal tissues, as well as the possible relation between well- and poorly-differentiated tumors. METHODS: A tissue array consisting of seven different tumors was generated. The tissue array included 120 points of esophagus, 120 points of stomach, 80 points of rectum, 60 points of thyroid gland, 100 points of mammary gland, 80 points ofliver, and 80 points of colon. Expressions of Tp53, C-myc, and CCND1 were determined by RNA in situ hybridization. 3' terminal digoxin-labeled anti-sense single stranded oligonucleotide and locked nucleic acid modifying probe were used.RESULTS: The expression level of Tp53 gene was higher in six different carcinoma tissue samples than in paracancerous tissue samples with the exception in colon carcinoma tissue samples (P < 0.05). The expression level of CCND1 gene was significantly different in different carcinoma tissue samples with the exception in esophagus and colon carcinoma tissue samples. The expression level of C-myc gene was different in esophagus carcinoma tissue samples (x2 = 18.495, P = 0.000), stomach carcinoma tissue samples (x2 = 23.750, P = 0.000), and thyroid gland tissue samples (x2 = 10.999, P = 0.004). The intensity of signals was also different in different carcinoma tissue samples and paracancerous tissue samples.CONCLUSION: Over-expression of the Tp53, CCND1, and C-myc genes appears to play a role in development of human cancer by regulating the expression of mRNA. Tp53, CCND1 and C-myc genes are significantly correlated with the development of different carcinomas.

  8. K-RAS point mutation, and amplification of C-MYC and C-ERBB2 in colon adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Tadeusz Pawełczyk

    2004-10-01

    Full Text Available The routine multidisciplinary management of colon cancer is based mainly on tumor staging, histology, grading and vascular invasion. In this approach, important individual information derived from molecular characteristics of the tumor may be missed, especially since significant heterogeneity of molecular aberrations in cancer cells has been observed, and recognition of every of relationships between them may be of value. K-RAS, C-MYC and C-ERBB2 are protooncogenes taking part in carcinogenesis and tumor progression in the colon. They influence cell proliferation, differentiation and survival. K-RAS point mutation, as well as amplification of C-MYC and C-ERBB2 were searched in 84 primary colon adenocarcinomas resected with curative intent. Multiplex polymerase-chain reaction and restriction fragment length polymorphism were performed to assess codon 12 K-RAS point mutation. Amplification of C-MYC and C-ERBB2 genes was evaluated by densitometry after agarose gel separation of the respective multiplex PCR products. No relation was found among mutated and/or amplified genes, and between searched molecular aberrations and pathoclinical features. In multivariate analysis, nodal status appeared to be the only independent prognostic indicator. In colon adenocarcinoma, codon 12 K-RAS point mutation and amplification of C-MYC and C-ERBB2 seem to occur independently in the process of tumor progression. Amplification of C-ERBB2 tends to associate with more advanced stage of disease. Concomitant occurrence of codon 12 K-RAS mutation, C-MYC and C-ERBB2 amplification was of no prognostic value in respect to survival.

  9. Clinical significance of high c-MYC and low MYCBP2 expression and their association with Ikaros dysfunction in adult acute lymphoblastic leukemia.

    Science.gov (United States)

    Ge, Zheng; Guo, Xing; Li, Jianyong; Hartman, Melanie; Kawasawa, Yuka Imamura; Dovat, Sinisa; Song, Chunhua

    2015-12-01

    Increased expression of c-MYC is observed in both Acute Myeloid Leukemia (AML) and T-cell Acute Lymphoblastic Leukemia (T-ALL). MYC binding protein 2 (MYCBP2) is a probable E3 ubiquitin ligase and its function in leukemia is unknown. IKZF1 deletion is associated with the development and poor outcome of ALL. Here, we observed significant high c-MYC expression and low MYCBP2 expression in adult ALL patients. Patients with high c-MYC expression and/or low MYCBP2 expression had higher WBC counts and a higher percentage of CD34+ or CD33+ cells, as well as splenomegaly, liver infiltration, higher BM blasts, and lower CR rate. Ikaros bound to the regulatory regions of c-MYC and MYCBP2, suppressed c-MYC and increased MYCBP2 expression in ALL cells. Expression of c-MYC mRNA was significantly higher in patients with IKZF1 deletion; conversely MYCBP2 mRNA expression was significantly lower in those patients. A CK2 inhibitor, which acts as an Ikaros activator, also suppressed c-MYC and increased MYCBP2 expression in an Ikaros (IKZF1) dependent manner in the ALL cells. In summary, our data indicated the correlation of high c-MYC expression, low MYCBP2 expression and high c-MYC plus low MYCBP2 expression with high-risk factors and proliferation markers in adult ALL patients. Our data also revealed an oncogenic role for an Ikaros/MYCBP2/c-MYC axis in adult ALL, providing a mechanism of target therapies that activate Ikaros in adult ALL.

  10. Kaempferol enhances cisplatin's effect on ovarian cancer cells through promoting apoptosis caused by down regulation of cMyc

    Directory of Open Access Journals (Sweden)

    Jiang Bing-Hua

    2010-05-01

    Full Text Available Abstract Background Ovarian cancer is one of the most significant malignancies in the western world. Studies showed that Ovarian cancers tend to grow resistance to cisplatin treatment. Therefore, new approaches are needed in ovarian cancer treatment. Kaempferol is a dietary flavonoid that is widely distributed in fruits and vegetables, and epidemiology studies have revealed a protective effect of kaempferol against ovarian cancer risk. Our early studies also found that kaempferol is effective in reducing vascular endothelial growth factor (VEGF expression in ovarian cancer cells. In this study, we investigated kaempferol's effects on sensitizing ovarian cancer cell growth in response to cisplatin treatment. Results Ten chemicals were screened for sensitizing OVCAR-3 ovarian cancer cell growth in response to cisplatin treatment. For kaempferol, which shows a significant synergistic interaction with cisplatin, expression of ABCC1, ABCC5, ABCC6, NFkB1, cMyc, and CDKN1A genes was further examined. For cisplatin/kaempferol treatments on OVCAR-3 cancer cells, the mRNA levels of ABCC1, ABCC5, and NFkB1 did not change. However, significant inhibition of ABCC6 and cMyc mRNA levels was observed for the cisplatin/kaempferol combined treatment. The CDKN1A mRNA levels were significantly up-regulated by cisplatin/kaempferol treatment. A plot of CDKN1A mRNA levels against that of cMyc gene further revealed a reverse, linear relationship, proving cMyc's regulation on CDKN1A gene expressions. Our work found that kaempferol works synergistically with cisplatin in inhibiting ovarian cancer cell viability, and their inhibition on cell viabilities was induced through inhibiting ABCC6 and cMyc gene transcription. Apoptosis assay showed the addition of 20 μM kaempferol to the cisplatin treatment induces the apoptosis of the cancer cells. Conclusions Kaempferol enhances the effect of cisplatin through down regulation of cMyc in promoting apoptosis of ovarian cancer

  11. Co-overexpression of bcl-2 and c-myc in uterine cervix carcinomas and premalignant lesions

    Directory of Open Access Journals (Sweden)

    Z. Protrka

    2011-03-01

    Full Text Available To establish the role of co-overexpression of bcl-2 and c-myc protooncogenes in uterine cervix carcinogenesis, we examined 138 tissue samples of low grade cervical squamous intraepithelial lesions (SIL, high grade SIL, portio vaginalis uteri (PVU carcinoma in situ and PVU carcinoma invasive, stage IA-IIA (study group and 36 samples without SIL or malignancy (control group. The expression of bcl-2 and c-myc was detected immunohistochemically using a monoclonal antibody. Fisher’s exact test (P<0.05 was used to assess statistical significance. Overexpression of bcl-2 was found to increase in direct relation to the grade of the cervical lesions. High sensitivity was of great diagnostic significance for the detection of these types of changes in the uterine cervix. On the basis of high predictive values it can be said that in patients with bcl-2 overexpression there is a great possibility that they have premalignant or malignant changes in the uterine cervix. Co-overexpression of bcl-2 and c-myc oncogenes was found only in patients with PVU invasive carcinoma (6/26-23.0%. Statistically significant difference was not found in the frequency of co-overexpression in patients with PVU invasive carcinoma in relation to the control group (Fisher’s test; P=0.064. The method's sensitivity of determining these oncogenes with the aim of detecting PVU invasive carcinoma was 23%, while specificity was 72.2%. On the basis of high predictive values (100%, speaking in statistical terms, it can be concluded that all patients with co-overexpression of bcl-2 and c-myc oncogenes will have PVU invasive carcinoma. We confirmed in our research that co-overexpression of bcl-2 and c-myc oncogenes was increased only in PVU invasive carcinoma. However, a more extensive series of samples and additional tests are required to establish the prognostic significance of bcl-2 and c-myc co-overexpression in cervical carcinogenesis.

  12. Mitochondrial structure, function and dynamics are temporally controlled by c-Myc.

    Directory of Open Access Journals (Sweden)

    J Anthony Graves

    Full Text Available Although the c-Myc (Myc oncoprotein controls mitochondrial biogenesis and multiple enzymes involved in oxidative phosphorylation (OXPHOS, the coordination of these events and the mechanistic underpinnings of their regulation remain largely unexplored. We show here that re-expression of Myc in myc-/- fibroblasts is accompanied by a gradual accumulation of mitochondrial biomass and by increases in membrane polarization and mitochondrial fusion. A correction of OXPHOS deficiency is also seen, although structural abnormalities in electron transport chain complexes (ETC are not entirely normalized. Conversely, the down-regulation of Myc leads to a gradual decrease in mitochondrial mass and a more rapid loss of fusion and membrane potential. Increases in the levels of proteins specifically involved in mitochondrial fission and fusion support the idea that Myc affects mitochondrial mass by influencing both of these processes, albeit favoring the latter. The ETC defects that persist following Myc restoration may represent metabolic adaptations, as mitochondrial function is re-directed away from producing ATP to providing a source of metabolic precursors demanded by the transformed cell.

  13. RNAi delivery by exosome-mimetic nanovesicles - Implications for targeting c-Myc in cancer.

    Science.gov (United States)

    Lunavat, Taral R; Jang, Su Chul; Nilsson, Lisa; Park, Hyun Taek; Repiska, Gabriela; Lässer, Cecilia; Nilsson, Jonas A; Gho, Yong Song; Lötvall, Jan

    2016-09-01

    To develop RNA-based therapeutics, it is crucial to create delivery vectors that transport the RNA molecule into the cell cytoplasm. Naturally released exosomes vesicles (also called "Extracellular Vesicles") have been proposed as possible RNAi carriers, but their yield is relatively small in any cell culture system. We have previously generated exosome-mimetic nanovesicles (NV) by serial extrusions of cells through nano-sized filters, which results in 100-times higher yield of extracellular vesicles. We here test 1) whether NV can be loaded with siRNA exogenously and endogenously, 2) whether the siRNA-loaded NV are taken up by recipient cells, and 3) whether the siRNA can induce functional knock-down responses in recipient cells. A siRNA against GFP was first loaded into NV by electroporation, or a c-Myc shRNA was expressed inside of the cells. The NV were efficiently loaded with siRNA with both techniques, were taken up by recipient cells, which resulted in attenuation of target gene expression. In conclusion, our study suggests that exosome-mimetic nanovesicles can be a platform for RNAi delivery to cell cytoplasm. PMID:27344366

  14. A STUDY OF C-MYC ONCOGENE EXPRESSIONAND AMPLIFICATION IN COLORECTAL CANCER

    Institute of Scientific and Technical Information of China (English)

    王建明; 李凌; 李申德; 崔惠云; 沈桂华

    1994-01-01

    Expression of c-myc oncogene transcripts in colorectal neoplasia was studied in paraffin embedded tissus sec-tions from 25 patients undergoin surgery and from the rectal carcinoma cell line HR-8348 by using in situ hy-bridization,and its amplification was investigated in tumor and normal mucosa tissue from 25 coloproctomy sam-ples by slot blot hybridization.Overexpression of this gene was seen in 78%(7/9)of the benign adenomas and 91%(20/22)of the malignancies sampled.There was no significant correlation between overexpression and the histologic type or grade,and no significant relationship between the level of expression and clinical stage was found,although overexpression was apparently more common in tumors with metastasis.Ampli-fication was also found in 2 adenomas with malignant change.The results suggest that multiple factors are in-volved in the progression of colorectal cancer,and in situ hybridization with nonradiolabeled probe is useful in the detection of gene expression.

  15. Induction of Pluripotency in Adult Equine Fibroblasts without c-MYC

    Directory of Open Access Journals (Sweden)

    Khodadad Khodadadi

    2012-01-01

    Full Text Available Despite tremendous efforts on isolation of pluripotent equine embryonic stem (ES cells, to date there are few reports about successful isolation of ESCs and no report of in vivo differentiation of this important companion species. We report the induction of pluripotency in adult equine fibroblasts via retroviral transduction with three transcription factors using OCT4, SOX2, and KLF4 in the absence of c-MYC. The cell lines were maintained beyond 27 passages (more than 11 months and characterized. The equine iPS (EiPS cells stained positive for alkaline phosphatase by histochemical staining and expressed OCT4, NANOG, SSEA1, and SSEA4. Gene expression analysis of the cells showed the expression of OCT4, SOX2 NANOG, and STAT3. The cell lines retained a euploid chromosome count of 64 after long-term culture cryopreservation. The EiPS demonstrated differentiation capacity for the three embryonic germ layers both in vitro by embryoid bodies (EBs formation and in vivo by teratoma formation. In conclusion, we report the derivation of iPS cells from equine adult fibroblasts and long-term maintenance using either of the three reprogramming factors.

  16. Inhibition of c-MYC with involvement of ERK/JNK/MAPK and AKT pathways as a novel mechanism for shikonin and its derivatives in killing leukemia cells.

    Science.gov (United States)

    Zhao, Qiaoli; Assimopoulou, Andreana N; Klauck, Sabine M; Damianakos, Harilaos; Chinou, Ioanna; Kretschmer, Nadine; Rios, José-Luis; Papageorgiou, Vassilios P; Bauer, Rudolf; Efferth, Thomas

    2015-11-17

    Leukemia remains life-threatening despite remarkable advances in chemotherapy. The poor prognosis and drug resistance are challenging treatment. Novel drugs are urgently needed. Shikonin, a natural naphthoquinone, has been previously shown by us to be particularly effective towards various leukemia cell lines compared to solid tumors. However, the underlying mechanisms are still poorly understood. Here, we investigated shikonin and 14 derivatives on U937 leukemia cells. Four derivatives (isobutyrylshikonin, 2-methylbutyrylshikonin, isovalerylshikonin and β,β-dimethylacrylshikonin) were more active than shikonin. AnnexinV-PI analysis revealed that shikonins induced apoptosis. Cell cycle G1/S check point regulation and the transcription factor c-MYC, which plays a vital role in cell cycle regulation and proliferation, were identified as the most commonly down-regulated mechanisms upon treatment with shikonins in mRNA microarray hybridizations. Western blotting and DNA-binding assays confirmed the inhibition of c-MYC expression and transcriptional activity by shikonins. Reduction of c-MYC expression was closely associated with deregulated ERK, JNK MAPK and AKT activity, indicating their involvement in shikonin-triggered c-MYC inactivation. Molecular docking studies revealed that shikonin and its derivatives bind to the same DNA-binding domain of c-MYC as the known c-MYC inhibitors 10058-F4 and 10074-G5. This finding indicates that shikonins bind to c-MYC. The effect of shikonin on U937 cells was confirmed in other leukemia cell lines (Jurkat, Molt4, CCRF-CEM, and multidrug-resistant CEM/ADR5000), where shikonin also inhibited c-MYC expression and influenced phosphorylation of AKT, ERK1/2, and SAPK/JNK. In summary, inhibition of c-MYC and related pathways represents a novel mechanism of shikonin and its derivatives to explain their anti-leukemic activity. PMID:26472107

  17. Anchoring of c-myc on nuclear matrix proteins in process of mouse thymic T lymphocyte proliferation induced by ConA

    Institute of Scientific and Technical Information of China (English)

    曾丛梅; 蔡树涛; 周凤兰; 张锦珠; 王平

    1996-01-01

    Isolation and characteriation of functional nudear matrix proteins involved in DNA anchoring and gene expression is one of the major subjects of current nudear matrix research. Southwestern blotting (DNA-protein hybridization) was applied to studying the anchoring of c-myc on the nudear matrix proteins in mouse thymic T lymphocytes. The results showed that c-myc bound to the lamin, p34 and p36 nudear matrix proteins specifically. In the process of mouse thymic PNA T lymphocytes proliferation induced by ConA, the anchoring of c-myc on p34 and p36 nudear matrix proteins changed dynamically.

  18. Tumor suppressor DYRK1A effects on proliferation and chemoresistance of AML cells by downregulating c-Myc.

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    Full Text Available Acute myeloid leukemia (AML, caused by abnormal proliferation and accumulation of hematopoietic progenitor cells, is one of the most common malignancies in adults. We reported here DYRK1A expression level was reduced in the bone marrow of adult AML patients, comparing to normal controls. Overexpression of DYRK1A inhibited the proliferation of AML cell lines by increasing the proportion of cells undergoing G0/G1 phase. We reasoned that the proliferative inhibition was due to downregulation of c-Myc by DYRK1A, through mediating its degradation. Moreover, overexpression of c-Myc markedly reversed AML cell growth inhibition induced by DYRK1A. DYRK1A also had significantly lower expression in relapsed/refractory AML patients, comparing to newly-diagnosed AML patients, which indicated the role of DYRK1A in chemoresistance of AML. Our study provided functional evidences for DYRK1A as a potential tumor suppressor in AML.

  19. Polymorphisms cMyc-N11S and p27-V109G and breast cancer risk and prognosis

    International Nuclear Information System (INIS)

    cMyc and p27 are key genes implicated in carcinogenesis. Whether polymorphisms in these genes affect breast cancer risk or prognosis is still unclear. In this study, we focus on a rare non-synonymous polymorphism in cMyc (N11S) and a common polymorphism in p27 (V109G) and determine their role in risk and prognosis using data collected from the Ontario Breast Cancer Family Registry. Risk factor data was collected at baseline on a large group of women (cases = 1,115 and population-based controls = 710) and clinical data (including treatment and follow-up) were collected prospectively by periodic review of medical records for a subset of cases (N = 967) for nearly a decade. A centralized pathology review was conducted. Unconditional logistic regression was used to determine the association of polymorphisms with breast cancer risk and the Cox proportional hazards model was used to determine their association with survival. Our results suggest that while cMyc-N11S can be considered a putatively functional polymorphism located in the N-terminal domain, it is not associated with risk, tumor characteristics or survival. The p27-G109 allele was associated with a modest protective effect in adjusted analyses and higher T stage. We found no evidence to suggest that p27-V109G alone or in combination with cMyc-N11S was associated with survival. Age at onset and first-degree family history of breast or ovarian cancer did not significantly modify the association of these polymorphisms with breast cancer risk. Further work is recommended to understand the potential functional role of these specific non-synonymous amino acid changes and a larger, more comprehensive investigation of genetic variation in these genes (e.g., using a tagSNP approach) in combination with other relevant genes is needed as well as consideration for treatment effects when assessing their potential role in prognosis

  20. Conserved features of cancer cells define their sensitivity to HAMLET-induced death; c-Myc and glycolysis.

    Science.gov (United States)

    Storm, P; Aits, S; Puthia, M K; Urbano, A; Northen, T; Powers, S; Bowen, B; Chao, Y; Reindl, W; Lee, D Y; Sullivan, N L; Zhang, J; Trulsson, M; Yang, H; Watson, J D; Svanborg, C

    2011-12-01

    HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here, we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small-hairpin RNA (shRNA) inhibition, proteomic and metabolomic technology, we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, HAMLET sensitivity was modified by the glycolytic state of tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen, hexokinase 1 (HK1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 and hypoxia-inducible factor 1α modified HAMLET sensitivity. HK1 was shown to bind HAMLET in a protein array containing ∼8000 targets, and HK activity decreased within 15 min of HAMLET treatment, before morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 min. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene addiction or the Warburg effect.

  1. Acinar-to-ductal metaplasia accompanies c-myc-induced exocrine pancreatic cancer progression in transgenic rodents.

    Science.gov (United States)

    Grippo, Paul J; Sandgren, Eric P

    2012-09-01

    Several important characteristics of exocrine pancreatic tumor pathogenesis remain incompletely defined, including identification of the cell of origin. Most human pancreatic neoplasms are ductal adenocarcinomas. However, acinar cells have been proposed as the source of some ductal neoplasms through a process of acinar-to-ductal metaplasia. The oncogenic transcription factor c-myc is associated with human pancreatic neoplasms. Transgenic mice overexpressing c-myc under control of acinar cell-specific elastase (Ela) gene regulatory elements not only develop acinar cell carcinomas but also mixed neoplasms that display both acinar-like neoplastic cells and duct-like neoplastic cells. In this report, we demonstrate that, first, c-myc is sufficient to induce acinar hyperplasia, though neoplastic lesions develop focally. Second, cell proliferation remains elevated in the neoplastic duct cell compartment of mixed neoplasms. Third, the proliferation/apoptosis ratio in cells from all lesion types remains constant, suggesting that differential regulation of these processes is not a feature of cancer progression in this model. Fourth, before the development of mixed neoplasms, there is transcriptional activation of the duct cell-specific cytokeratin-19 gene promoter in multicellular foci of amylase-positive acinar neoplasms. This observation provides direct evidence for metaplasia as the mechanism underlying development of ductal neoplastic cells within the context of an acinar neoplasm and suggests that the stimulus for this transformation acts over a multicellular domain or field within a neoplasm. Finally, focal ductal elements develop in some acinar cell carcinomas in Ela-c-myc transgenic rats, indicating that myc-associated acinar-to-ductal metaplasia is not restricted to the mouse.

  2. Focal Adhesion Kinase Is Required for Intestinal Regeneration and Tumorigenesis Downstream of Wnt/c-Myc Signaling

    OpenAIRE

    Ashton, Gabrielle H.; Morton, Jennifer P; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan

    2010-01-01

    The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. Given Wnt/c-Myc signaling is activated following intestinal regeneration, we investigated the functional importance of FAK following deletion of the Apc tumor suppressor protein withi...

  3. c-Myc Enhances Sonic Hedgehog-Induced Medulloblastoma Formation from Nestin-Expressing Neural Progenitors in Mice1

    OpenAIRE

    Rao, Ganesh; Pedone, Carolyn A; Coffin, Cheryl M.; Holland, Eric C.; Fults, Daniel W.

    2003-01-01

    Medulloblastomas are malignant brain tumors that arise in the cerebella of children. The presumed cells-of-origin are undifferentiated precursors of granule neurons that occupy the external granule layer (EGL) of the developing cerebellum. The overexpression of proteins that normally stimulate proliferation of neural progenitor cells may initiate medulloblastoma formation. Two known mitogens for neural progenitors are the c-Myc oncoprotein and Sonic hedgehog (Shh), a crucial determinant of em...

  4. Targeting C-myc G-Quadruplex: Dual Recognition by Aminosugar-Bisbenzimidazoles with Varying Linker Lengths

    Directory of Open Access Journals (Sweden)

    Nihar Ranjan

    2013-11-01

    Full Text Available G-quadruplexes are therapeutically important biological targets. In this report, we present biophysical studies of neomycin-Hoechst 33258 conjugates binding to a G-quadruplex derived from the C-myc promoter sequence. Our studies indicate that conjugation of neomycin to a G-quadruplex binder, Hoechst 33258, enhances its binding. The enhancement in G-quadruplex binding of these conjugates varies with the length and composition of the linkers joining the neomycin and Hoechst 33258 units.

  5. A natural small molecule, catechol, induces c-Myc degradation by directly targeting ERK2 in lung cancer

    Science.gov (United States)

    Lim, Do Young; Shin, Seung Ho; Lee, Mee-Hyun; Malakhova, Margarita; Kurinov, Igor; Wu, Qiong; Xu, Jinglong; Jiang, Yanan; Dong, Ziming; Liu, Kangdong; Lee, Kun Yeong; Bae, Ki Beom; Choi, Bu Young; Deng, Yibin; Bode, Ann; Dong, Zigang

    2016-01-01

    Various carcinogens induce EGFR/RAS/MAPK signaling, which is critical in the development of lung cancer. In particular, constitutive activation of extracellular signal-regulated kinase 2 (ERK2) is observed in many lung cancer patients, and therefore developing compounds capable of targeting ERK2 in lung carcinogenesis could be beneficial. We examined the therapeutic effect of catechol in lung cancer treatment. Catechol suppressed anchorage-independent growth of murine KP2 and human H460 lung cancer cell lines in a dose-dependent manner. Catechol inhibited ERK2 kinase activity in vitro, and its direct binding to the ERK2 active site was confirmed by X-ray crystallography. Phosphorylation of c-Myc, a substrate of ERK2, was decreased in catechol-treated lung cancer cells and resulted in reduced protein stability and subsequent down-regulation of total c-Myc. Treatment with catechol induced G1 phase arrest in lung cancer cells and decreased protein expression related to G1-S progression. In addition, we showed that catechol inhibited the growth of both allograft and xenograft lung cancer tumors in vivo. In summary, catechol exerted inhibitory effects on the ERK2/c-Myc signaling axis to reduce lung cancer tumor growth in vitro and in vivo, including a preclinical patient-derived xenograft (PDX) model. These findings suggest that catechol, a natural small molecule, possesses potential as a novel therapeutic agent against lung carcinogenesis in future clinical approaches. PMID:27167001

  6. The Influence of Nano-apatite on c-myc and p53 Gene in the Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    CHEN Jun; CAO Xianying; LI Shipu; HAN Yingchao; ZHANG Ran

    2005-01-01

    The influence mechanism of the nano-apatite on the human hepatocellular carcinoma in vitro was investigated. Using the homogeneous precipitation method, the nano-apatite was synthesized at room temperature, and it was characterized with transmission electron microscopy (TEM) and the Zataplus. The influence on the expression of the c-myc and p53 gene in the human hepatocellular carcinoma cell lines were tested with the TEM and hybridization in situ. The TEM and the Zataplus analyses show that the nano-apatite is distributed homogenously in size and needle-shaped sizes, which ranges from 67.5 nm to 88.3 nm. It is found that the nano-apatitet increases the volume of the human hepatocellular carcinoma cells, makes extensive cytoplasmic vacuolization, the mitochondria swelling, chromatin in nucleus dispersed partially and condensed around the nuclear membranes.The interspace in nuclear membranes were separated and even the cytoplasm dissolved. It is also found that the expression of the c-myc gene is inhibited, but the p53 is enhanced. The experimental results demonstrate that the nano-apatite enables the oncosis of the human hepatocellular carcinoma cells by down-regulation of the expression of the c-myc and up-regulation of the expression of the p53 in vitro.

  7. Ginger extract inhibits human telomerase reverse transcriptase and c-Myc expression in A549 lung cancer cells.

    Science.gov (United States)

    Tuntiwechapikul, Wirote; Taka, Thanachai; Songsomboon, Chonnipa; Kaewtunjai, Navakoon; Imsumran, Arisa; Makonkawkeyoon, Luksana; Pompimon, Wilart; Lee, T Randall

    2010-12-01

    The rhizome of ginger (Zingiber officinale Roscoe) has been reputed to have many curative properties in traditional medicine, and recent publications have also shown that many agents in ginger possess anticancer properties. Here we show that the ethyl acetate fraction of ginger extract can inhibit the expression of the two prominent molecular targets of cancer, the human telomerase reverse transcriptase (hTERT) and c-Myc, in A549 lung cancer cells in a time- and concentration-dependent manner. The treated cells exhibited diminished telomerase activity because of reduced protein production rather than direct inhibition of telomerase. The reduction of hTERT expression coincided with the reduction of c-Myc expression, which is one of the hTERT transcription factors; thus, the reduction in hTERT expression might be due in part to the decrease of c-Myc. As both telomerase inhibition and Myc inhibition are cancer-specific targets for cancer therapy, ginger extract might prove to be beneficial as a complementary agent in cancer prevention and maintenance therapy. PMID:21091248

  8. Primary structure and functional scFv antibody expression of an antibody against the human protooncogen c-myc.

    Science.gov (United States)

    Fuchs, P; Breitling, F; Little, M; Dübel, S

    1997-06-01

    The immunoglobulin heavy- and light-chain variable region (Vh and Vl) genes were isolated from Myc1-9E10 hybridoma cells, which secreted monoclonal antibody against human oncogen c-myc. The expression vector pOPE52-c-myc was constructed for the recombinant production in E. coli. A 30 kDa single chain fragment (scFv) expression product was found in the periplasmic space by SDS-PAGE and immunoblotting. A significant fraction was processed correctly as demonstrated with an antiserum recognizing the processed aminoterminus only. The specific binding of the scFv fragment to the peptide epitope of the maternal monoclonal antibody was demonstrated and the primary sequence of the variable regions was determined. Sequence comparison with previously published partial Vh and Vl sequences from this hybridoma cell line revealed a genetic heterogeneity for the light chain variable region. The potential use of this scFv as a new tool for detection and purification of tagged proteins, for adding costimulatory signals to the surface of cancer cells as well as for analyzing c-myc function in the living cell by cytoplasmic expression is discussed.

  9. C-Myc regulates substrate oxidation patterns during early pressure-overload hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena R. [Seattle Children' s Research Inst., Seattle, WA (United States); Smith, Lincoln [Seattle Children' s Hospital, Seattle, WA (United States); Kajimoto, Masaki [Seattle Children' s Research Inst., Seattle, WA (United States); Bruce, Margaret [Seattle Children' s Research Inst., Seattle, WA (United States); Isern, Nancy G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL); Xu, Chun [Seattle Children' s Research Inst., Seattle, WA (United States); Portman, Michael A. [Seattle Children' s Research Inst., Seattle, WA (United States); Olson, Aaron [Seattle Children' s Research Inst., Seattle, WA (United States)

    2013-11-26

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of glycolytic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected FVB mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketones and unlabeled glucose and insulin. Western blots were used to evaluate metabolic enzymes. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (presumably glucose) contribution. Myc inactivation (MycKO-TAC) inhibited these metabolic changes. Hypertrophy in general increased protein levels of PKM2; however this change was not linked to Myc status. Protein post-translation modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. In conclusion, Myc regulates substrate utilization during early pressure overload hypertrophy. Our results show that the metabolic switch during hypertrophy is not necessary to maintain cardiac function, but it may be important mechanism to promote cardiomyocyte growth. Myc also regulates protein O-GlcNAcylation during hypertrophy.

  10. c-Myc and AMPK Control Cellular Energy Levels by Cooperatively Regulating Mitochondrial Structure and Function.

    Directory of Open Access Journals (Sweden)

    Lia R Edmunds

    Full Text Available The c-Myc (Myc oncoprotein and AMP-activated protein kinase (AMPK regulate glycolysis and oxidative phosphorylation (Oxphos although often for different purposes. Because Myc over-expression depletes ATP with the resultant activation of AMPK, we explored the potential co-dependency of and cross-talk between these proteins by comparing the consequences of acute Myc induction in ampk+/+ (WT and ampk-/- (KO murine embryo fibroblasts (MEFs. KO MEFs showed a higher basal rate of glycolysis than WT MEFs and an appropriate increase in response to activation of a Myc-estrogen receptor (MycER fusion protein. However, KO MEFs had a diminished ability to increase Oxphos, mitochondrial mass and reactive oxygen species in response to MycER activation. Other differences between WT and KO MEFs, either in the basal state or following MycER induction, included abnormalities in electron transport chain function, levels of TCA cycle-related oxidoreductases and cytoplasmic and mitochondrial redox states. Transcriptional profiling of pathways pertinent to glycolysis, Oxphos and mitochondrial structure and function also uncovered significant differences between WT and KO MEFs and their response to MycER activation. Finally, an unbiased mass-spectrometry (MS-based survey capable of quantifying ~40% of all mitochondrial proteins, showed about 15% of them to be AMPK- and/or Myc-dependent in their steady state. Significant differences in the activities of the rate-limiting enzymes pyruvate kinase and pyruvate dehydrogenase, which dictate pyruvate and acetyl coenzyme A abundance, were also differentially responsive to Myc and AMPK and could account for some of the differences in basal metabolite levels that were also detected by MS. Thus, Myc and AMPK are highly co-dependent and appear to engage in significant cross-talk across numerous pathways which support metabolic and ATP-generating functions.

  11. Use of a transfected and amplified Drosophila heat shock promoter construction for inducible production of toxic mouse c-myc proteins in CHO cells

    International Nuclear Information System (INIS)

    After transfection and selection with methotrexate, CHO cell lines were established which contained up to 2000 copies of an expression vector for c-myc protein. The vector contained the Drosophila heat shock protein 70 (hsp70) promoter fused with the coding region of the mouse c-myc gene. Incubation of cells for up to 3 hours at 430C resulted in at least a 100-fold induction of recombinant c-myc mRNA. When cells were shifted back to 370C, within 1 to 4 hours, this RNA was translated into protein to yield about 250 μg per 109 cells. Cells died a few hours later, suggesting that high concentrations of intracellular c-myc are cytotoxic. 47 refs., 5 figs

  12. c-Myc Transforms Human Mammary Epithelial Cells through Repression of the Wnt Inhibitors DKK1 and SFRP1▿ †

    Science.gov (United States)

    Cowling, Victoria H.; D'Cruz, Celina M.; Chodosh, Lewis A.; Cole, Michael D.

    2007-01-01

    c-myc is frequently amplified in breast cancer; however, the mechanism of myc-induced mammary epithelial cell transformation has not been defined. We show that c-Myc induces a profound morphological transformation in human mammary epithelial cells and anchorage-independent growth. c-Myc suppresses the Wnt inhibitors DKK1 and SFRP1, and derepression of DKK1 or SFRP1 reduces Myc-dependent transforming activity. Myc-dependent repression of DKK1 and SFRP1 is accompanied by Wnt target gene activation and endogenous T-cell factor activity. Myc-induced mouse mammary tumors have repressed SFRP1 and increased expression of Wnt target genes. DKK1 and SFRP1 inhibit the transformed phenotype of breast cancer cell lines, and DKK1 inhibits tumor formation. We propose a positive feedback loop for activation of the c-myc and Wnt pathways in breast cancer. PMID:17485441

  13. Use of a transfected and amplified Drosophila heat shock promoter construction for inducible production of toxic mouse c-myc proteins in CHO cells

    Energy Technology Data Exchange (ETDEWEB)

    Wurm, F.M.; Gwinn, K.A.; Papoulas, O.; Pallavicini, M.; Kingston, R.E.

    1987-07-24

    After transfection and selection with methotrexate, CHO cell lines were established which contained up to 2000 copies of an expression vector for c-myc protein. The vector contained the Drosophila heat shock protein 70 (hsp70) promoter fused with the coding region of the mouse c-myc gene. Incubation of cells for up to 3 hours at 43/sup 0/C resulted in at least a 100-fold induction of recombinant c-myc mRNA. When cells were shifted back to 37/sup 0/C, within 1 to 4 hours, this RNA was translated into protein to yield about 250 ..mu..g per 10/sup 9/ cells. Cells died a few hours later, suggesting that high concentrations of intracellular c-myc are cytotoxic. 47 refs., 5 figs.

  14. Down-regulation of Thanatos-associated protein 11 by BCR-ABL promotes CML cell proliferation through c-Myc expression.

    Science.gov (United States)

    Nakamura, Satoki; Yokota, Daisuke; Tan, Lin; Nagata, Yasuyuki; Takemura, Tomonari; Hirano, Isao; Shigeno, Kazuyuki; Shibata, Kiyoshi; Fujisawa, Shinya; Ohnishi, Kazunori

    2012-03-01

    Bcr-Abl activates various signaling pathways in chronic myelogenous leukemia (CML) cells. The proliferation of Bcr-Abl transformed cells is promoted by c-Myc through the activation of Akt, JAK2 and NF-κB. However, the mechanism by which c-Myc regulates CML cell proliferation is unclear. In our study, we investigated the role of Thanatos-associated protein 11 (THAP11), which inhibits c-Myc transcription, in CML cell lines and in hematopoietic progenitor cells derived from CML patients. The induction of THAP11 expression by Abl kinase inhibitors in CML cell lines and in CML-derived hematopoietic progenitor cells resulted in the suppression of c-Myc. In addition, over-expression of THAP11 inhibited CML cell proliferation. In colony forming cells derived from CML-aldehyde dehydrogenase (ALDH)(hi) /CD34(+) cells, treatment with Abl kinase inhibitors and siRNA depletion of Bcr-Abl induced THAP11 expression and reduced c-Myc expression, resulting in inhibited colony formation. Moreover, overexpression of THAP11 significantly decreased the colony numbers, and also inhibited the expression of c-myc target genes such as Cyclin D1, ODC and induced the expression of p21(Cip1) . The depletion of THAP11 inhibited JAK2 or STAT5 inactivation-mediated c-Myc reduction in ALDH(hi) /CD34(+) CML cells. Thus, the induced THAP11 might be one of transcriptional regulators of c-Myc expression in CML cell. Therefore, the induction of THAP11 has a potential possibility as a target for the inhibition of CML cell proliferation. PMID:21400515

  15. Decoding c-Myc networks of cell cycle and apoptosis regulated genes in a transgenic mouse model of papillary lung adenocarcinomas.

    Science.gov (United States)

    Ciribilli, Yari; Singh, Prashant; Spanel, Reinhard; Inga, Alberto; Borlak, Jürgen

    2015-10-13

    The c-Myc gene codes for a basic-helix-loop-helix-leucine zipper transcription factor protein and is reported to be frequently over-expressed in human cancers. Given that c-Myc plays an essential role in neoplastic transformation we wished to define its activity in lung cancer and therefore studied its targeted expression to respiratory epithelium in a transgenic mouse disease model. Using histological well-defined tumors, transcriptome analysis identified novel c-Myc responsive cell cycle and apoptosis genes that were validated as direct c-Myc targets using EMSA, Western blotting, gene reporter and ChIP assays.Through computational analyses c-Myc cooperating transcription factors emerged for repressed and up-regulated genes in cancer samples, namely Klf7, Gata3, Sox18, p53 and Elf5 and Cebpα, respectively. Conversely, at promoters of genes regulated in transgenic but non-carcinomatous lung tissue enriched binding sites for c-Myc, Hbp1, Hif1 were observed. Bioinformatic analysis of tumor transcriptomic data revealed regulatory gene networks and highlighted mortalin and moesin as master regulators while gene reporter and ChIP assays in the H1299 lung cancer cell line as well as cross-examination of published ChIP-sequence data of 7 human and 2 mouse cell lines provided strong evidence for the identified genes to be c-Myc targets. The clinical significance of findings was established by evaluating expression of orthologous proteins in human lung cancer. Taken collectively, a molecular circuit for c-Myc-dependent cellular transformation was identified and the network analysis broadened the perspective for molecularly targeted therapies.

  16. Self-assembly of c-myc DNA promoted by a single enantiomer ruthenium complex as a potential nuclear targeting gene carrier

    Science.gov (United States)

    Wu, Qiong; Mei, Wenjie; Zheng, Kangdi; Ding, Yang

    2016-01-01

    Gene therapy has long been limited in the clinic, due in part to the lack of safety and efficacy of the gene carrier. Herein, a single enantiomer ruthenium(II) complex, Λ-[Ru(bpy)2(p-BEPIP)](ClO4)2 (Λ-RM0627, bpy = 4,4′-bipyridine, p-BEPIP = 2-(4-phenylacetylenephenyl)imidazole [4,5f][1, 10] phenanthroline), has been synthesized and investigated as a potential gene carrier that targets the nucleus. In this report, it is shown that Λ-RM0627 promotes self-assembly of c-myc DNA to form a nanowire structure. Further studies showed that the nano-assembly of c-myc DNA that induced Λ-RM0627 could be efficiently taken up and enriched in the nuclei of HepG2 cells. After treatment of the nano-assembly of c-myc DNA with Λ-RM0627, over-expression of c-myc in HepG2 cells was observed. In summary, Λ-RM0627 played a key role in the transfer and release of c-myc into cells, which strongly indicates Λ-RM0627 as a potent carrier of c-myc DNA that targets the nucleus of tumor cells. PMID:27381008

  17. Three-dimensional imaging of the metabolic state of c-MYC-induced mammary tumor with the cryo-imager

    Science.gov (United States)

    Zhang, Zhihong; Liu, Qian; Luo, Qingming; Zhang, Min Z.; Blessington, Dana M.; Zhou, Lanlan; Chodosh, Lewis A.; Zheng, Gang; Chance, Britton

    2003-07-01

    This study imaged the metabolic state of a growing tumor and the relationship between energy metabolism and the ability of glucose uptake in whole tumor tissue with cryo-imaging at 77° K. A MTB/TOM mouse model, bearing c-MYC-induced mammary tumor, was very rapidly freeze-trapped 2 hrs post Pyro-2DG injection. The fluorescence signals of oxidized flavoprotein (Fp), reduced pyridine nucleotide (PN), pyro-2DG, and the reflection signal of deoxy-hemoglobin were imaged every 100 μm from the top surface to the bottom of the tumor sequentially, 9 sections in total. Each of the four signals was constructed into 3D images with Amira software. Both Fp and PN signals could be detected in the growing tumor regions, and a higher reduction state where was shown in the ratio images. The necrotic tumor regions displayed a very strong Fp signal and weak PN signal. In the bloody extravasation regions, Fp and PN signals were observably diminished. Therefore, the regions of high growth and necrosis in the tumor could be determined according to the Fp and PN signals. The content of deoxy-hemoglobin (Hb) in the tumor was positively correlated with the reduced PN signal. Pyro-2DG signal was only evident in the growing condition region in the tumor. Normalized 3D cross-correlation showed that Pyro-2DG signal was similar to the redox ratio. The results indicated that glucose uptake in the tumor was consistent with the redox state of the tumor. And both Pyro-2DG and mitochondrial NADH fluorescence showed bimodal histograms suggesting that the two population of c-MYC induced mammary tumor, one of which could be controlled by c-MYC transgene.

  18. Regulation of human ornithine decarboxylase expression following prolonged quiescence: role for the c-Myc/Max protein complex.

    Science.gov (United States)

    Peña, A; Wu, S; Hickok, N J; Soprano, D R; Soprano, K J

    1995-02-01

    WI-38 cells can remain quiescent for long periods of time and still be induced to reenter the cell cycle by the addition of fresh serum. However, the longer these cells remain growth arrested, the more time they require to enter S phase. This prolongation of the prereplicative phase has been localized to a point early in G1, after the induction of "immediate early" G1 genes such as c-fos and c-jun but before maximal expression of "early" G1 genes such as ornithine decarboxylase (ODC). Understanding the molecular basis for ODC mRNA induction can therefore provide information about the molecular events which regulate the progression of cells out of long-term quiescence into G1 and subsequently into DNA synthesis. Studies utilizing electrophoretic mobility shift assays (EMSA) of nuclear extracts from short- and long-term quiescent WI-38 cells identified a region of the human ODC promoter at -491 bp to -474 bp which exhibited a protein binding pattern that correlated with the temporal pattern of ODC mRNA expression. The presence of a CACGTG element within this fragment, studies with antibodies against c-Myc and Max, the use of purified recombinant c-Myc protein in the mobility shift assay, and antisense studies suggest that these proteins can specifically bind this portion of the human ODC promoter in a manner consistent with growth-associated modulation of the expression of ODC and other early G1 genes following prolonged quiescence. These studies suggest a role for the c-Myc/Max protein complex in regulating events involved in the progression of cells out of long-term quiescence into G1 and subsequently into S.

  19. Suppression of c-myc expression by lentiviral vector-mediatedsmall interfering RNA in Jiyoye cells%慢病毒载体介导的siRNA抑制Jiyoye细胞c-myc基因表达的实验研究

    Institute of Scientific and Technical Information of China (English)

    宋爱琴; 鞠秀丽; 孙立; 王玲; 李晓玲; 于洪升

    2011-01-01

    Objective To explore the effect of lentiviral vector-mediated siRNA on c-myc gene expression in Jiyoye cells by using the RNAi technique in vitro.Methods Three interference sequences c-myc-1, c-myc-2 and c-myc-3 and the negative control c-myc-neg that targeted human c-myc mRNA were designed and synthesized.After annealing, all the fragments were cloned into the pLVX vector, which were transfected into human leukemia Jiyoye ceils by lentivirus and were cultured for 72 hours.The cells were divided into five groups: the blank control group(untransfected), the cmyc-neg group, the c-myc-1 group, the c-myc-2 group and the c-myc-3 group.After 72 hours, the transfection rate in each group was determined by flow cytometry.Expressions of the c-myc mRNA and c-Myc protein were detected by Real-time PCR and Western blot.Results PLVX-c-myc-neg, PLVX-c-myc-1, PLVX-c-myc-2 and PLVX-c-myc-3were constructed.C-myc mRNA and protein expression levels in the three groups respectively transfected with c-myc-1,c-myc-2 and c-myc-3 were significantly down-regulated compared with the negative control group transfected with c-mycneg(P <0.05).The c-myc-3 group decreased most significantly compared with the c-myc-1 group and the c-myc-2 group ( P < 0.05 ).There was no significant difference between the untransfected group and the negative control group ( P > 0.05 ).Conclusion The successfully constructed shRNA expression vector for the c-myc gene suppresses expression of c-myc in Jiyoye cells, which might provide an experimental basis for further study of the role of c-myc gene silencing in targeting treatment of leukemia and lymphoma.%目的 探讨RNAi技术经慢病毒载体介导的siRNA对Jiyoye细胞c-myc基因表达的抑制作用.方法 设计并合成RNA干扰序列,退火后连接到pLVX干扰载体上,构建PLVX-c-myc表达载体,经慢病毒介导转染人Jiyoye细胞株培养72 h.实验分为空白对照(未转染)、c-myc-neg、c-myc-1、c-myc-2、c-myc-3组.采用流式细

  20. Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma.

    OpenAIRE

    Pelicci, P.G.; Knowles, D M; Magrath, I; Dalla-Favera, R

    1986-01-01

    We have examined the position of the chromosomal breakpoint relative to the human c-myc gene (MYC) and the presence of other structural alterations of the same locus in 19 fresh samples of Burkitt lymphoma (BL) and 13 BL-derived cell lines. This panel includes the two pathogenetic forms of BL: the endemic (African-type) BL (eBL) and sporadic (American-type) BL (sBL). In all cases tested, including fresh samples and cell lines, structural alterations of the 5' portion of the gene were detected...

  1. In vivo distribution of c-myc antisense oligodeoxynucleotides local delivered by gelatin-coated platinmn-iridium stents in rabbits and its effect on apoptosis

    Institute of Scientific and Technical Information of China (English)

    张新霞; 崔长琮; 许香广; 胡雪松; 方卫华; 邝碧娟

    2004-01-01

    Background Post-stenting restenosis is a significant clinical problem, involving vascular smooth muscle cells(VSMCs) proliferation and apoptosis. It is reported that c-myc antisense oligodeoxynucleotides (ASODNs) local delivered by catheter can inhibit VSMCs proliferation. This study was designed to assess tissue distribution of c-myc ASODN local delivered using gelatin-coated platinum-iridium (Pt-Ir) stents, and its effect on apoptosis of VSMCs. Methods Gelatin-coated Pt-Ir stents that had absorbed caroboxyfluorescein-5-succimidyl ester (FAM) labeled c-myc ASODNs (550 μg per stent) were implanted into the right carotid arteries of 6 rabbits. Tissue samples were obtained at 45 minutes, 2 hours, and 6 hours. Tissue distribution of c- myc ASODNs was assessed by fluorescence microscopy. In addition, 32 rabbits were randomly divided into two groups. Rabbits in the control group (n=16) were implanted with gelatin-coated Pt-Ir stents, and those in the treatment group (n=16) were implanted with gelatin-coated stents that had absorbed c-myc ASODNs. 7, 14, 30, or 90 days (n=4, respectively, for each group) after the stenting procedure, the stented segments were harvested, and histopathological examinations were performed to calculate neointimal area and mean neointimal thickness. The expression of c-myc was assessed using in situ hybridization (ISH) and immunohistochemical methods. Apoptotic VSMCs were detected using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and transmission electron microscope (TEM). Results According to fluorescence microscopic results, FAM-labeled c-myc ASODNs were concentrated in the target vessel media at the 45 minutes time point, and then dispersed to the adventitia. Morphometric analysis showed that neointimal area and mean neointimal thickness increased continuously up to 90 days after stent implantation, but that total neointimal area and mean neointimal thickness were less in the treatment group than in the

  2. Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Kyung-Soo [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Park, Jun-Ik [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Mi-Ju; Kim, Hak-Bong; Lee, Jae-Won [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Dao, Trong Tuan; Oh, Won Keun [BK21 Project Team, College of Pharmacy, Chosun University, Gwangju (Korea, Republic of); Kang, Chi-Dug, E-mail: kcdshbw@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Sun-Hee, E-mail: ksh7738@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

    2012-03-01

    SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia

  3. Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

    International Nuclear Information System (INIS)

    SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia

  4. The long non-coding RNA PARROT is an upstream regulator of c-Myc and affects proliferation and translation

    Science.gov (United States)

    Vučićević, Dubravka; Gehre, Maja; Dhamija, Sonam; Friis-Hansen, Lennart; Meierhofer, David; Sauer, Sascha; Ørom, Ulf Andersson

    2016-01-01

    Long non-coding RNAs are important regulators of gene expression and signaling pathways. The expression of long ncRNAs is dysregulated in cancer and other diseases. The identification and characterization of long ncRNAs is often challenging due to their low expression level and localization to chromatin. Here, we identify a functional long ncRNA, PARROT (Proliferation Associated RNA and Regulator Of Translation) transcribed by RNA polymerase II and expressed at a relatively high level in a number of cell lines. The PARROT long ncRNA is associated with proliferation in both transformed and normal cell lines. We characterize the long ncRNA PARROT as an upstream regulator of c-Myc affecting cellular proliferation and translation using RNA sequencing and mass spectrometry following depletion of the long ncRNA. PARROT is repressed during senescence of human mammary epithelial cells and overexpressed in some cancers, suggesting an important association with proliferation through regulation of c-Myc. With this study, we add to the knowledge of cytoplasmic functional long ncRNAs and extent the long ncRNA-Myc regulatory network in transformed and normal cells. PMID:27129154

  5. Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice

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    Liao Dezhong J

    2008-01-01

    Full Text Available Abstract Background Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials. Results Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT and liver metastatic lesions (LM compared to normal pancreas (NP. In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1 and Serine proteinase inhibitor A1 (Serpina1, and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples. Conclusion We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed.

  6. Local Delivery of C-myc Antisense Oligodeoxynucleotide by Gelatin Coated Platinium-Iridium Stent to Prevent Restenosis in a Normal Rabbit Carotid Artery

    Institute of Scientific and Technical Information of China (English)

    Zhang Xinxia; Wei Wenbin; Duan Wen; Xu Xiangguang; Hu Xuesong

    2005-01-01

    Objectives To investigate the feasibility and effect of local deliveryof c-myc antisense oligodeoxynucleotide (ASODN) by gelatin coated Platinium-Iridium stent to prevent restenosis in a normal rabbit carotid artery. Methods Gelatin coated Platinium-Iridium stent were implanted in the right carotid arteries of 32 rabbits under vision. Animals were randomized to the control group and the treated group receiving c-myc ASODN (n=16 respectively).7,14,30,90 days following the stenting procedure,morphometry for caculation of neointimal area and mean neointimal thickness were performed.The expression of c-myc protein was detected by immunohistochemical methods. Results 32 stents were successfully implanted into the right carotid arteries in 32 animals. Morphometric analysis showed that neointimal area and mean neointimal thickness siginificantly increased continuously up to 12 weeks after stent implantation,and at each time point ,neointimal area and mean neointimal thickness were siginificantly smaller in the treated group than control group. (P<0.001 ,respectively).c-myc protein expression was weak positive or negative in treated group and positive in control group. Conclusions Gelatin coated Platinium-Iridium stent mediated local delivery of c-myc ASODN is feasibility , and it can inhibit neointimal hyperplasia to prevent restenosis in a normal rabbit carotid artery.

  7. Farnesiferol c induces apoptosis via regulation of L11 and c-Myc with combinational potential with anticancer drugs in non-small-cell lung cancers.

    Science.gov (United States)

    Jung, Ji Hoon; Kim, Moon Joon; Lee, Hyemin; Lee, Jihyun; Kim, Jaekwang; Lee, Hyun Joo; Shin, Eun Ah; Kim, Yoon Hyeon; Kim, Bonglee; Shim, Bum Sang; Kim, Sung-Hoon

    2016-01-01

    Though Farnesiferol c (FC) has been reported to have anti-angiogenic and antitumor activity, the underlying antitumor mechanism of FC still remains unclear. Thus, in the present study, we investigated the apoptotic mechanism of FC in human H1299 and H596 non-small lung cancer cells (NSCLCs). FC significantly showed cytotoxicity, increased sub-G1 accumulation, and attenuated the expression of Bcl-2, Bcl-xL, Survivin and procaspase 3 in H1299 and H596 cells. Furthermore, FC effectively suppressed the mRNA expression of G1 arrest related genes such as Cyclin D1, E2F1 transcription factor and CDC25A by RT-PCR. Interestingly, FC inhibited the expression of c-Myc, ribosomal protein L11 (L11) and nucleolin (NCL) in H1299 and H596 cells. Of note, silencing of L11 by siRNA transfection enhanced the expression of c-Myc through a negative feedback mechanism, while c-Myc knockdown downregulated L11 in H1299 cells. Additionally, combined treatment of FC and puromycin/doxorubicin promoted the activation of caspase 9/3, and attenuated the expression of c-Myc, Cyclin D1 and CDK4 in H1299 cells compared to single treatment. Taken together, our findings suggest that FC induces apoptosis and G1 arrest via regulation of ribosomal protein L11 and c-Myc and also enhances antitumor effect of puromycin or doxorubicin in NSCLCs. PMID:27231235

  8. Correlation of chromosomal polysomy with overexpression of c-myc and c-erbB-2 in primary nasopharyngeal carcinoma: Tissue microarray study

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Many genes may be involved in nasopharyngeal carcinoma (NPC) development and progression. Several known oncogenes, including c-myc and c-erb-B2, have been shown to have structural alteration and aberrant expression in NPC. Here, we constructed a tissue microarray to determine the status of c-myc and c-erbB-2 oncogenes at the DNA and protein levels using interphase fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) and to define the diagnostic, prognostic importance of the genetic changes. Results showed that amplification of c-myc and c-erbB-2 was not found in NPC. Polysomy 8 and 17 were observed in 43%-50% and 20%-27% of NPC tumors, respectively. Overexpressions of c-myc and c-erbB-2 oncoproteins were detected in 53.6% and 54.5% cases of NPC with polysomy 8 and 17, respectively. There was no significant correlation between c-myc and c-erbB-2 staining and the clinical stage. But overexpression of c-erbB-2 was associated with polysomy 17 in NPC. These findings suggest that chromosomal polysomy, not gene amplification, may be partially responsible for the upregulated expression of c-erbB-2 oncogene in NPC.

  9. Expression of telomerase hTERT in human non-small cell lung cancer and its correlation with c-myc gene

    Institute of Scientific and Technical Information of China (English)

    耿志华; 张敦华; 刘银坤

    2003-01-01

    Objective To investigate the expression of human telomerase catalytic subunit, hTERT, in human non-small cell lung cancer (NSCLC) and its correlations to c-myc gene.Methods hTERT and c-myc mRNA expressions were detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Statistical correlation analysis was made to estimate whether there was interrelation between them.Results Positive rate of hTERT expression in 51 surgically resected lung cancer specimens was 86.3%, significantly higher than that in adjacent non-neoplastic lung tissues and benign lesions, which were 14.3% and 27.3% respectively. No statistical significance was observed between the frequency of hTERT expression and histologic types, degree of differentiation, TNM stages, tumor size or lymph nodes metastases. Correlation analysis revealed that the expression of c-myc gene was significantly related to that of hTERT (correlation coefficient, r=0.633, P<0.001).Conclusions hTERT may be a useful tumor marker in diagnosing lung cancer. Significant correlation between the expression of hTERT and c-myc mRNA indicates that the activation and up-regulation of hTERT might be conferred by over-expression of c-myc gene.

  10. Expressions of beta-catenin, APC Protein, C-myc and Cyclin D1 in Ovarian Epithelial Tumor and Their Implication

    Institute of Scientific and Technical Information of China (English)

    LIN Xiao; LI Yu; MI Can

    2007-01-01

    Objective: To investigate the expressions of beta-catenin, protein APC (adenomatous polyposis coli protein), c-myc and cyclin D1 and their implication in ovarian epithelial tumor. Methods: Immunohistochemical staining with SP method was conducted to identify the expressions of beta-catenin, APC protein, c-myc and cyclin D1 in ovarian epithelial tumor in 48 cases. Results: The abnormal expression rate of beta-catenin in malignant and borderline ovarian epithelial tumors was higher than that in benign epithelial tumors (P<0.01). The expression rates of c-myc and cyclin-D1 in ovarian malignant and borderline epithelial tumors were higher than those in benign epithelial tumors too(P<0.05). The prevalence of APC protein positive expression in benign epithelial tumors were significantly greater than that in malignant epithelial tumors (P<0.05). A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors; while a significant positive correlation was found between beta-catenin, c-myc and cyclin-D1 in ovarian epithelial tumor (P<0.05). Conclusion: The abnormal expressions of Beta-catenin, APC protein, c-myc and cyclin-D1 might be used to indicate the malignance transform of ovarian epithelial tumors.

  11. cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas

    DEFF Research Database (Denmark)

    Manfè, Valentina; Biskup, Edyta; Willumsgaard, Ayalah;

    2013-01-01

    improve their clinical efficacy. Using cutaneous T-cell lymphoma (CTCL) as a model of the chemotherapy-resistant peripheral lymphoid malignancy, we demonstrated that resistance to proteasome inhibition involved a signaling between the oncogene cMyc and miR-125b-5p. Bortezomib repressed cMyc...... and simultaneously induced miR-125b-5p that exerted a cytoprotective effect through the downmodulation of MAD4. Overexpression of cMyc repressed miR-125b-5p transcription and sensitized lymphoma cells to bortezomib. The central role of miR-125b-5p was further confirmed in a mouse model of T-cell lymphoma, where...

  12. SALL4 as an Epithelial-Mesenchymal Transition and Drug Resistance Inducer through the Regulation of c-Myc in Endometrial Cancer.

    Directory of Open Access Journals (Sweden)

    Lei Liu

    Full Text Available SALL4 plays important roles in the development and progression of many cancers. However, the role and molecular mechanism of SALL4 in endometrial cancer remain elusive. In the present research, we have demonstrated that the expression of SALL4 was upregulated in endometrial cancer and correlated positively with tumor stage, metastases and poor survival of patients. The overexpression of SALL4 promoted the invasiveness in endometrial cancer cells, as indicated by the upregulation of mesenchymal cell marker N-cadherin and downregulation of the epithelial marker E-cadherin, and invasion assays in vitro. Additionally, there was also an increase in drug resistance in these cell models due to the upregulation of ATP-binding cassette multidrug transporter ABCB1 expression. Moreover, we also found that ABCB1 was critical for SALL4-induced drug resistance. In contrast, SALL4 knockdown restored drug sensitivity, reversed EMT, diminished cell metastasis and suppressed the downregulation of E-cadherin and the upregulation of N-cadherin and ABCB1. Furthermore, we showed that SALL4 upregulated c-Myc expression and c-Myc was a direct target for SALL4 by ChIP assay, depletion of c-Myc with siRNA abolished the SALL4-induced downregulation of E-cadherin, upregulation of N-cadherin and ABCB1, suggesting that c-Myc was a downstream target for SALL4 and required for SALL4-induced EMT, invasion and drugs resistance in endometrial cancer cells. These results indicated that SALL4 could induce EMT and resistance to antineoplastic drugs through the regulation of c-Myc. SALL4 and c-Myc may be novel therapeutic targets for endometrial cancer.

  13. Detection of HER-2/neu, c-myc amplification and p53 inactivation by FISH in Egyptian patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Mohamed, Hanaa M.

    2009-05-01

    Full Text Available Breast cancer is a leading cause of cancer-related deaths in women worldwide. The clinical course of this disease is highly variable and clinicians continuously search for prognostic parameters that can accurately predict prognosis, and indicate a suitable adjuvant therapy for each patient. Amplification of the two oncogenes HER-2/neu and c-myc and inactivation of the tumor suppressor gene p53 are frequently encountered in breast carcinomas. The purpose of this study was to use the fluorescence in situ hybridization (FISH for the assessment of HER-2/neu and c-myc amplification and p53 inactivation and to relate these molecular markers with the commonly used clinical and pathological factors. The study was conducted on 34 tissue samples obtained from 33 females and 1 male with breast carcinomas and 17 samples obtained from 16 females and 1 male with benign breast lesions. Results revealed that the level of HER-2/neu, c-myc and p53 in the malignant group was significantly increased as compared to the benign group. On relating the level of the molecular markers to clinicopathological factors, p53 was significantly associated with increased patient’s age. The sensitivity of the investigated markers significantly increased with larger tumor size. Concerning tumor grade, HER-2/neu and p53 showed a significant increase in low-grade tumors whereas c-myc showed a highly significant increase in high-grade tumors. With regard to disease staging, HER-2/neu and c-myc were the only markers that showed significant increase at late stages of disease. p53 and HER-2/neu were significantly associated with positive lymph nodal status. A significant correlation was obtained between the levels of the three biomarkers to each other. Conclusively, the combination of HER-2/neu, c-myc and p53 can stratify patients into different risk groups.

  14. Detection of HER-2/neu, c-myc amplification and p53 inactivation by FISH in Egyptian patients with breast cancer.

    Science.gov (United States)

    Ismail, Manal F; Aly, Magdy Sayed; Khaled, Hussein M; Mohamed, Hanaa M

    2009-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. The clinical course of this disease is highly variable and clinicians continuously search for prognostic parameters that can accurately predict prognosis, and indicate a suitable adjuvant therapy for each patient. Amplification of the two oncogenes HER-2/neu and c-myc and inactivation of the tumor suppressor gene p53 are frequently encountered in breast carcinomas. The purpose of this study was to use the fluorescence in situ hybridization (FISH) for the assessment of HER-2/neu and c-myc amplification and p53 inactivation and to relate these molecular markers with the commonly used clinical and pathological factors. The study was conducted on 34 tissue samples obtained from 33 females and 1 male with breast carcinomas and 17 samples obtained from 16 females and 1 male with benign breast lesions. Results revealed that the level of HER-2/neu, c-myc and p53 in the malignant group was significantly increased as compared to the benign group. On relating the level of the molecular markers to clinicopathological factors, p53 was significantly associated with increased patient's age. The sensitivity of the investigated markers significantly increased with larger tumor size. Concerning tumor grade, HER-2/neu and p53 showed a significant increase in low-grade tumors whereas c-myc showed a highly significant increase in high-grade tumors. With regard to disease staging, HER-2/neu and c-myc were the only markers that showed significant increase at late stages of disease. p53 and HER-2/neu were significantly associated with positive lymph nodal status. A significant correlation was obtained between the levels of the three biomarkers to each other. Conclusively, the combination of HER-2/neu, c-myc and p53 can stratify patients into different risk groups. PMID:19675743

  15. Investigating actinomycin D binding to G-quadruplex, i-motif and double-stranded DNA in 27-nt segment of c-MYC gene promoter.

    Science.gov (United States)

    Niknezhad, Zhila; Hassani, Leila; Norouzi, Davood

    2016-01-01

    c-MYC DNA is an attractive target for drug design, especially for cancer chemotherapy. Around 90% of c-MYC transcription is controlled by NHE III1, whose 27-nt purine-rich strand has the ability to form G-quadruplex structure. In this investigation, interaction of ActD with 27-nt G-rich strand (G/c-MYC) and its equimolar mixture with the complementary sequence, (GC/c-MYC) as well as related C-rich oligonucleotide (C/c-MYC) was evaluated. Molecular dynamic simulations showed that phenoxazine and lactone rings of ActD come close to the outer G-tetrad nucleotides indicating that ActD binds through end-stacking to the quadruplex DNA. RMSD and RMSF revealed that fluctuation of the quadruplex DNA increases upon interaction with the drug. The results of spectrophotometry and spectrofluorometry indicated that ActD most probably binds to the c-MYC quadruplex and duplex DNA via end-stacking and intercalation, respectively and polarity of ActD environment decreases due to the interaction. It was also found that binding of ActD to the GC-rich DNA is stronger than the two other forms of DNA. Circular dichroism results showed that the type of the three forms of DNA structures doesn't change, but their compactness alters due to their interaction with ActD. Finally, it can be concluded that ActD binds differently to double stranded DNA, quadruplex DNA and i-motif.

  16. Identification of a c-Jun N-terminal kinase-2-dependent signal amplification cascade that regulates c-Myc levels in ras transformation

    DEFF Research Database (Denmark)

    Mathiasen, D.P.; Egebjerg, C.; Andersen, S.H.;

    2012-01-01

    Ras is one of the most frequently activated oncogenes in cancer. Two mitogen-activated protein kinases (MAPKs) are important for ras transformation: extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase 2 (JNK2). Here we present a downstream signal amplification cascade that is...... essential for ras transformation. Previous studies show that ERK-mediated serine 62 phosphorylation protects c-Myc from proteasomal degradation. ERK is, however, not alone sufficient to stabilize c-Myc but requires the cooperation of cancerous inhibitor of protein phosphatase 2A (CIP2A), an oncogene that...

  17. Identification of functional networks of estrogen- and c-Myc-responsive genes and their relationship to response to tamoxifen therapy in breast cancer.

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    Elizabeth A Musgrove

    Full Text Available BACKGROUND: Estrogen is a pivotal regulator of cell proliferation in the normal breast and breast cancer. Endocrine therapies targeting the estrogen receptor are effective in breast cancer, but their success is limited by intrinsic and acquired resistance. METHODOLOGY/PRINCIPAL FINDINGS: With the goal of gaining mechanistic insights into estrogen action and endocrine resistance, we classified estrogen-regulated genes by function, and determined the relationship between functionally-related genesets and the response to tamoxifen in breast cancer patients. Estrogen-responsive genes were identified by transcript profiling of MCF-7 breast cancer cells. Pathway analysis based on functional annotation of these estrogen-regulated genes identified gene signatures with known or predicted roles in cell cycle control, cell growth (i.e. ribosome biogenesis and protein synthesis, cell death/survival signaling and transcriptional regulation. Since inducible expression of c-Myc in antiestrogen-arrested cells can recapitulate many of the effects of estrogen on molecular endpoints related to cell cycle progression, the estrogen-regulated genes that were also targets of c-Myc were identified using cells inducibly expressing c-Myc. Selected genes classified as estrogen and c-Myc targets displayed similar levels of regulation by estrogen and c-Myc and were not estrogen-regulated in the presence of siMyc. Genes regulated by c-Myc accounted for 50% of all acutely estrogen-regulated genes but comprised 85% (110/129 genes in the cell growth signature. siRNA-mediated inhibition of c-Myc induction impaired estrogen regulation of ribosome biogenesis and protein synthesis, consistent with the prediction that estrogen regulates cell growth principally via c-Myc. The 'cell cycle', 'cell growth' and 'cell death' gene signatures each identified patients with an attenuated response in a cohort of 246 tamoxifen-treated patients. In multivariate analysis the cell death signature

  18. Nucleolus disassembly in mitosis and apoptosis: dynamic redistribution of phosphorylated-c-Myc, fibrillarin and Ki-67

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    C Soldani

    2009-06-01

    Full Text Available The nucleolus may undergo disassembly either reversibly during mitosis, or irreversibly in apoptosis, thus allowing the redistribution of the nucleolar proteins.We investigated here by immunocytochemistry the fate of three representative proteins, namely phosphorylated c-Myc, fibrillarin and Ki-67, and found that they behave independently in both processes: they relocate in distinct compartments during mitosis, whereas during apoptosis they may either be cleaved (Ki-67 or be extruded into the cytoplasm with a different kinetics and following an ordered, non chaotic program. The separation of these nucleolar proteins which occurs in early apoptotic nuclei continues also in the cytoplasm, and culminates in the final formation of apoptotic blebs containing different nucleolar proteins: this evidence confirms that the apoptotic bodies may be variable in size, content and surface reactivity, and include heterogeneous aggregates of nuclear proteins and/or nucleic acids.

  19. EFFECT OF HYPOXIA ON DNA SYNTHESIS AND C-MYC GENE EXPRESSION OF PULMONARY ARTERY SMOOTH MUSCLE CELLS

    Institute of Scientific and Technical Information of China (English)

    罗兰; 李世强; 蔡英年

    1996-01-01

    The neonate is particularly susceptible to the development of hypoxie pulmonary hypertension. The present study was undertaken to observe the effect of hypoxia on DNA synthesis and c-mye gene expressionbetween newborn calf and adult bovine PASMC in vitro DNA synthesis measured by 3H-TdR incorporation was increased after hypoxie challenge for 24h. Hypoxia enhanced the increment in 3H-TdR incorporationinduced by EGF. Northern blot analysis revealed that PASMC cultured in both normoxia and hypoxia expressed c-mye gene transcript of 2.2Kb ,but there is a higher 2.2Kb mRNA expression in hypoxie PASMC than that in normoxia. We speculate that newborn calf PASMC exhibited potential response to hypoxia than adult,which was augmented by EGF. Enhanced c-myc gene expression may lead to a great understanding of the mechanism of PASMC growth in the development of pulmonary hypertension.

  20. THE HEPARIN-BINDING DOMAIN AND V REGION OF FIBRONECTIN REGULATE APOPTOSIS BY SUPPRESSION OF P53 AND C-MYC IN HUMAN PRIMARY CELLS

    Science.gov (United States)

    In apoptosis the tumor suppressor p53 and oncogene c-myc, are usually upregulated. However, we report here an alternate pathway of regulation that is triggered by inflammatory-associated matrix fragments of fibronectin (FN) and leads to apoptosis. It is mediated by transcriptio...

  1. Cooperation of c-raf-1 and c-myc protooncogenes in the neoplastic transformation of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Overexpression of c-raf-1 and the myc family of protooncogenes is primarily associated with small cell carcinoma, which accounts for ∼ 25% of human lung cancer. To determine the functional significance of the c-raf-1 and/or c-myc gene expression in lung carcinogenesis and to delineate the relationship between protooncogene expression and tumor phenotype, the authors introduced both protooncogenes, alone or in combination, into human bronchial epithelial cells. Two retroviral recombinants, pZip-raf and pZip-myc, containing the complete coding sequences of the human c-raf-1 and murine c-myc genes, respectively, were constructed and transfected into simian virus 40 large tumor antigen-immortalized bronchial epithelial cells (BEAS-2B); this was followed by selection for G418 resistance. Cell lines established from tumors (designated RMT) revealed the presence of the cotransfected c-raf-1 and c-myc sequences and expressed morphological, chromosomal, and isoenzyme markers, which identified BEAS-2B cells as the progenitor line of the tumors. The data demonstrate that the concomitant expression of the c-raf and c-myc protooncogenes causes neoplastic transformation of human bronchial epithelial cells resulting in large cell carcinomas with certain neuroendocrine markers. The presented model system should be useful in studies of molecular events involved in multistage lung carcinogenesis

  2. Effects of matrine on the growth inhibition, c-myc and hTERT protein expression in human adenocarcinoma lung cancer cell line A549

    Directory of Open Access Journals (Sweden)

    Qiong CHEN

    2008-08-01

    Full Text Available Background and objective It was reported that telomerase was associated with the oncogenesis and progression of cancer, and to be the common targets of cancer therapy. The mechanism of matrine on lung cancer in vitro is not clear. We studied the effect of matrine on growth of human lung adenocarcinoma A549 cells and the mechanism related with telomerase. Methods MTT was used for measuring A549 cells viability, Hoechst 33342-propidium iodide fluorescent staining for observing apoptotic cells, flow cytometry (FCM for analyzing cell cycle and apoptosis, and immunocytochemistry for measuring the protein expressions of c-myc and hTERT in A549 cells. Results Matrine inhibited the proliferation of A549 cells with a time-dose-dependent manner (P<0.05. Hoechst 33342-propidium iodide staining showed apoptotic cells with chromatin condensation and fragmentation of nuclei. FCM analysis indicated elevating rate of cells in G0/G1 phase, lowering rate of that in S phase and the highering apoptotic rate. The levels of c-myc and hTERT protein expression in the matrine group was lower than that in the control group (P<0.05, and AOD of c-myc showed positive correlation with AOD of hTERT (r=0.633, P<0.01 Conclusion The inhibitory effect of matrine on A549 cells may be related to the lower expression of c-myc and hTERT.

  3. The use of FISH-comet to detect c-Myc and TP 53 damage in extended-term lymphocyte cultures treated with terbuthylazine and carbofuran.

    Science.gov (United States)

    Mladinic, Marin; Zeljezic, Davor; Shaposhnikov, Sergey A; Collins, Andrew R

    2012-05-20

    Terbuthylazine and carbofuran are suspected to cause non-Hodgkin's lymphoma and lung cancer. We evaluated the effects of prolonged exposure to low concentrations on primary DNA damage by comet assay, and on the structural integrity of c-Myc and TP 53 genes by FISH-comet. Another novelty in studying these pesticides' genotoxicity is the use of 14-day extended-term human lymphocyte cultures. Concentrations corresponded to values of ADI and OEL: for terbuthylazine 0.58 ng/ml and 8 ng/ml; for carbofuran 8 ng/ml and 21.6 ng/ml, respectively. A possible effect of metabolic activation (S9) was also considered. Carbofuran treatment induced a significant migration of DNA into the tail in a concentration-dependent manner, while for terbuthylazine the effect was significant only at the higher concentration. Terbuthylazine caused migration of both c-Myc signals into the comet tail. A significant occurrence of TP 53 signals in the tail was observed at 8 ng/ml. Prolonged carbofuran treatment significantly elevated the migration of a single c-Myc signal into the tail in a concentration-dependent manner. With S9, distribution of signals shifted toward increased presence of both signals in tail. Our results showed impaired structural integrity of c-Myc and TP 53 due to prolonged exposure to terbuthylazine and carbofuran.

  4. EFFECT OF ACTIVE COMPOUNDS ISOLATED FROM PTERIS SEMIPINNATA L ON DNA TOPOISOMERASES AND TYROSINE PROTEIN KINASE AND EXPRESSION OF C-MYC IN LUNG ADENOCARCINOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    李金华; 梁念慈; 莫丽儿; 张晓; 何承伟

    2001-01-01

    Objective: To study the effect of active compound 6F and A from Pteris semipinnata L.(PsL) on the activities of DNA topoisomerase (TOPO) I and II, activities of cytosolic and membrane TPK, and expression of oncogene c-myc in lung adenocarcinoma cells. Methods: The effect of compound 6F and A on activities of cytosolic and membrane TPK was measured by scintillation counting; the effect of compound A on expression of oncogene c-myc was determined by flow cytometry indirect fluorimetry. Results: compound 6F and A could inhibit the activities of TOPO I, and they strongly inhibited the TOPO II in 0.01 mg/L and 10.0 mg/L respectively. Compound A slightly inhibited the activities of membrane TPK, but not the cytosolic one. Compound A could inhibit the expression of oncogene c-myc. Conclusion: Topoisomerases are target of compound 6F and A. Compound A could slightly inhibit the activities of TPK, and showed an inhibitory effect on the expression of oncogene c-myc.

  5. Function of apoptosis and expression of the proteins Bcl-2, p53 and C-myc in the development of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    An Gao Xu; Shao Guang Li; Ji Hong Liu; Ai Hua Gan

    2001-01-01

    @@INTRODUCTION In China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .

  6. Triplex-forming oligonucleotides targeting c-MYC potentiate the anti-tumor activity of gemcitabine in a mouse model of human cancer.

    Science.gov (United States)

    Boulware, Stephen B; Christensen, Laura A; Thames, Howard; Coghlan, Lezlee; Vasquez, Karen M; Finch, Rick A

    2014-09-01

    Antimetabolite chemotherapy remains an essential cancer treatment modality, but often produces only marginal benefit due to the lack of tumor specificity, the development of drug resistance, and the refractoriness of slowly proliferating cells in solid tumors. Here, we report a novel strategy to circumvent the proliferation-dependence of traditional antimetabolite-based therapies. Triplex-forming oligonucleotides (TFOs) were used to target site-specific DNA damage to the human c-MYC oncogene, thereby inducing replication-independent, unscheduled DNA repair synthesis (UDS) preferentially in the TFO-targeted region. The TFO-directed UDS facilitated incorporation of the antimetabolite, gemcitabine (GEM), into the damaged oncogene, thereby potentiating the anti-tumor activity of GEM. Mice bearing COLO 320DM human colon cancer xenografts (containing amplified c-MYC) were treated with a TFO targeted to c-MYC in combination with GEM. Tumor growth inhibition produced by the combination was significantly greater than with either TFO or GEM alone. Specific TFO binding to the genomic c-MYC gene was demonstrated, and TFO-induced DNA damage was confirmed by NBS1 accumulation, supporting a mechanism of enhanced efficacy of GEM via TFO-targeted DNA damage-induced UDS. Thus, coupling antimetabolite chemotherapeutics with a strategy that facilitates selective targeting of cells containing amplification of cancer-relevant genes can improve their activity against solid tumors, while possibly minimizing host toxicity. PMID:23681918

  7. Effect of Neem Leaf Extract (Azadirachta indica on c-MycOncogene Expression in 4T1 Breast Cancer Cells of BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Chong Pei Pei

    2012-01-01

    Full Text Available Objective: Breast cancer is the most common cause of cancer-related deaths in women both worldwide and in Malaysia. Azadirachta indica (A. Juss, commonly known as neem, is one of the most versatile medicinal plants that has gained worldwide prominence due to its medicinal properties. However, the anticancer effect of ethanolic neem leaf extract against breast cancer has not been documented. The purpose of the present study is to investigate the effect of neem leaf extract on c-Myc oncogene expression in 4T1 breast cancer BALB/c mice.Materials and Methods: In this experimental study, A total of 48 female BALB/c mice were divided randomly into four groups of 12 mice per group: i.cancer control (CC treated with 0.5% Tween 20 in PBS, ii. 0.5 μg/mL tamoxifen citrate (CT, iii. 250 mg/kg neem leaf extract (C250, and iv. 500 mg/kg neem leaf extract (C500. In situ reverse transcription polymerase chain reaction (in situ RT-PCR was applied to evaluate suppression of c-Myc oncogene expression in breast cancer tissue.Results: The C500 group showed significant (p<0.05 suppression of c-Myc oncogene expression compared to the CC group.Conclusion: c-Myc was found to be down regulated under the effect of 500 mg/kg ethanolicneem leaf extract.

  8. Labdane type diterpenes down-regulate the expression of c-Myc protein, but not of Bcl-2, in human leukemia T-cells undergoing apoptosis.

    Science.gov (United States)

    Dimas, K; Demetzos, C; Vaos, V; Ioannidis, P; Trangas, T

    2001-06-01

    Sclareol (1) and ent-3beta-hydroxy-13-epi-manoyl oxide (2) belong to the labdane type diterpenes. They were isolated from the leaves and from the fruits of Cistus creticus subsp. creticus, and were found to be active against human leukemic cell lines. Compound 2 was converted to its thiomidazolide derivative (3). Compounds 1 and 3 were found to induce apoptotic cell death in human T-cell leukemia lines and to interfere with their cell cycle, arresting cells at G(0/1) phase. Apoptosis can involve the activation and/or suppression of critical genes such as c-myc whose reduction or its inappropriate expression can be associated with induction of cell death and bcl-2 whose activation prevents apoptosis in the latter case. In order to detect any concomitant effect (1 and 3) upon c-myc and bcl-2 oncogene expression, we performed Western blot analysis to determine the levels of expression of these two genes upon treatment with the above compounds. Western blot analysis showed that of c-myc proto-oncogene levels were markedly reduced before massive apoptosis ensued in H33AJ-JA1 and MOLT3 cells, while bcl-2 expression remained unaffected. Thus, induction of apoptosis due to compounds 1 and 3 in these T-cell leukemic cell lines is preceded by c-myc down regulation and furthermore sustained bcl-2 expression does not rescue cells from apoptosis under the conditions used. PMID:11337016

  9. The inhibition effects of the c-myc targeting CRISPR/Cas9 adenovirus system on hepatoma cells%靶向 c-myc 基因的 CRISPR/Cas9腺病毒系统对肝癌的抑制作用

    Institute of Scientific and Technical Information of China (English)

    连竹生; 梁鑫; 金桂花; 吴领知; 韩苏夏

    2016-01-01

    目的:设计、构建并包装靶向 c-myc 基因的 CRISPR/Cas9腺病毒;评估靶向 c-myc 基因的 CRISPR/Cas9腺病毒系统对肝癌的抑制作用。方法:采用生物信息学网站设计靶向 c-myc 基因的 gRNA,以 GFP 作为对照设计GFP gRNA;通过 T7E1筛选出编辑效率高的 gRNA 并将筛选的 gRNA 构建 CRISPR/Cas9腺病毒载体并包装腺病毒,通过分析细胞增殖、周期和凋亡及迁移能力的变化来评估靶向 c-myc 基因的 CRISPR/Cas9腺病毒系统对肝癌的抑制作用。结果:成功设计、构建并包装靶向 c-myc 基因的 CRISPR/Cas9腺病毒;靶向 c-myc 基因的 CRISPR/Cas9腺病毒系统能够显著抑制 Hepa1-6细胞的增殖和迁移、阻滞细胞周期进程,但对细胞凋亡无影响。结论:靶向 c-myc 基因的 CRISPR/Cas9腺病毒系统可在细胞水平明显抑制肝癌细胞的生长。%Aim:To design,construct and package the CRISPR/Cas9 adenovirus system for targeting the mouse c-myc gene;To evaluate the inhibition efficiency of the constructed adenovirus system on c-myc gene in hepatoma cells.Methods:We designed gRNAs for targeting the mouse c-myc gcontrolene and used another gene (gRNAs for GFP)as control based on bioinformatics website.The editing efficiencies of these gRNAs were determined by T7E1 cleavage.The gRNAs with higher editing efficiency were se-lected and packed into adenovirus for the following experiments.Firstly,Hepa 1-6 cells were infected with the constructed adenovirus,then cell proliferation,cell cycle,cell apoptosis and migration assays were detected to de the inhibition efficiency of the adenovirus on hepatoma cells.Statistical analyses were performed with SPSS(version 18.0)and t-test,P <0.05 was considered statistically significant.Re-sults:The CRISPR/Cas9 adenovirus system targeting the mouse c-myc gene was successfully designed constructed and packaged.Compared with the control group,the experiment groups (with CRISPR/Cas9

  10. c-Myc quadruplex-forming sequence Pu-27 induces extensive damage in both telomeric and nontelomeric regions of DNA.

    Science.gov (United States)

    Islam, Md Ashraful; Thomas, Shelia D; Murty, Vundavalli V; Sedoris, Kara J; Miller, Donald M

    2014-03-21

    Quadruplex-forming DNA sequences are present throughout the eukaryotic genome, including in telomeric DNA. We have shown that the c-Myc promoter quadruplex-forming sequence Pu-27 selectively kills transformed cells (Sedoris, K. C., Thomas, S. D., Clarkson, C. R., Muench, D., Islam, A., Singh, R., and Miller, D. M. (2012) Genomic c-Myc quadruplex DNA selectively kills leukemia. Mol. Cancer Ther. 11, 66-76). In this study, we show that Pu-27 induces profound DNA damage, resulting in striking chromosomal abnormalities in the form of chromatid or chromosomal breaks, radial formation, and telomeric DNA loss, which induces γ-H2AX in U937 cells. Pu-27 down-regulates telomeric shelterin proteins, DNA damage response mediators (RAD17 and RAD50), double-stranded break repair molecule 53BP1, G2 checkpoint regulators (CHK1 and CHK2), and anti-apoptosis gene survivin. Interestingly, there are no changes of DNA repair molecules H2AX, BRCA1, and the telomere maintenance gene, hTERT. ΔB-U937, where U937 cells stably transfected with deleted basic domain of TRF2 is partially sensitive to Pu-27 but exhibits no changes in expression of shelterin proteins. However, there is an up-regulation of CHK1, CHK2, H2AX, BRCA1, and survivin. Telomere dysfunction-induced foci assay revealed co-association of TRF1with γ-H2AX in ATM deficient cells, which are differentially sensitive to Pu-27 than ATM proficient cells. Alt (alternating lengthening of telomere) cells are relatively resistant to Pu-27, but there are no significant changes of telomerase activity in both Alt and non-Alt cells. Lastly, we show that this Pu-27-mediated sensitivity is p53-independent. The data therefore support two conclusions. First, Pu-27 induces DNA damage within both telomeric and nontelomeric regions of the genome. Second, Pu-27-mediated telomeric damage is due, at least in part, to compromise of the telomeric shelterin protein complex.

  11. The function of apoptosis and protein expression of bcl-2, p53 and C-myc inthe development of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    An Gao Xu; Shao Guang Li; Ji Hong Liu; Ai Hua Gan

    2000-01-01

    AIM To understand the rule and possible function of apoptosis and protein expression of bcl-2, p53 and C-myc in chronic gastritis, gastric ulcer, non-classic proliferation of gastric mucosa and gastric cancer.METHODS Apoptosis was detected by using in situ terminal labelling (TUNEL). The protein expression ofbcl-2, p53 and C-myc was detected by immunohistochemical method.RESULTS The indexes of apoptosis in chronic active gastritis, gastric ulcer, mild and severe non-classicproliferation of gastric mucosa, early and progressive gastric cancer were 16.8%±12.3%, 24.1%±20.0%,19.3%±16.4%, 15.7%±15.2%, 10.1%±9.1% and 6.3%±6.0%, respectively. The index of progressivegastric cancer was lower than that of early gastric cancer and non-classic proliferation of gastric mucosa(P<0.05). The positive rate of bcl-2 protein was 9.4%, 27.6%, 52.9%, 75.0%, 83.3% and 46.7%,respectively. The positive rate of bcl-2 of early gastric cancer was higher than that of progressive gastriccancer. The positive rates of p53 protein of severe non-classic proliferation, early and progressive gastriccancer were 25.0%, 33.3% and 63.3%, respectively. The positive rate of p53 of progressive gastric cancerwas higher than that of early gastric cancer and non-classic proliferation (P<0.05). In Lauren types, theindex of apoptosis, protein expression rates of bcl-2, p53 and C-myc of intestinal type were 8.3%±7.2%,38.9%, 77.7% and 56.6%, while that of diffuse type were 5.1%±4.9%, 58.3%, 50.0% and 8.3%,respectively. All markers had statistical difference between two types (P<0.05).CONCLUSION Apoptosis was inhibited stepwise in the development of non-classic proliferation of gastricmucosa to early gastric cancer and then to progressive gastric cancer. The high expression of bcl-2, p53 andC-myc was related to the development of gastric cancer, bcl-2 might play an important role in early gastriccancer while p53 and C-myc act mostly in middle and late stage gastric cancer. The Lauren typing of

  12. DNA Damage, Apoptosis and C-myc, C-fos, and C-jun Overexpression Induced by Selenium in Rat Hepatocytes

    Institute of Scientific and Technical Information of China (English)

    RI-AN YU; CHENG-FENG YANG; XUE-MIN CHEN

    2006-01-01

    Objective To study the effects of selenium on DNA damage, apoptosis and c-myc, c-fos, and c-jun expression in rat hepatocytes. Methods Sodium selenite at the doses of 5, 10, and 20 μmol/kg was given to rats by i.p. and there were 5 male SD rats in each group. Hepatocellular DNA damage was detected by single cell gel electrophoresis (or comet assay).Hepatocellular apoptosis was determined by TUNEL (TdT-mediated dUTP nick end labelling) and flow cytometry. C-myc,c-fos, and c-jun expression in rat hepatocytes were assayed by Northern dot hybridization. C-myc, c-fos, and c-jun protein were detected by immunohistochemical method. Results At the doses of 5, 10, and 20 μmol/kg, DNA damage was induced by sodium selenite in rat hepatocytes and the rates of comet cells were 34.40%, 74.80%, and 91.40% respectively. Results also showed an obvious dose-response relationship between the rates of comet cells and the doses of sodium selenite (r=0.9501,P<0.01). Sodium selenite at the doses of 5, 10, and 20 μmol/kg caused c-myc, c-fos, and c-jun overexpression obviously. The positive brown-yellow signal for proteins of c-myc, c-fos, and c-jun was mainly located in the cytoplasm of hepatocytes with immunohistochemical method. TUNEL-positive cells were detected in selenium-treated rat livers. Apoptotic rates (%) of selenium-treated liver cells at the doses of 5, 10, and 20 μmol/kg were (3.72±1.76), (5.82±1.42), and (11.76±1.87) respectively, being much higher than those in the control. Besides an obvious dose-response relationship between apoptotic rates and the doses of sodium selenite (r=0.9897, P<0.01), these results displayed a close relationship between DNA damage rates and apoptotic rates, and the relative coefficient was 0.9021, P<0.01. Conclusion Selenium at 5-20 μmol/kg can induce DNA damage, apoptosis, and overexpression of c-myc, c-fos, and c-jun in rat hepatocytes.

  13. Pokemon、c-myc在结直肠癌中的表达及意义%EXPRESSION AND CLINICAL SIGNIFICANCE OF POKEMON AND C-MYC IN COLORECTAL CANCER

    Institute of Scientific and Technical Information of China (English)

    刘叔敏; 范玉磊; 梁婷婷; 孙影

    2014-01-01

    目的:探讨结直肠癌组织Pokemon和c-myc蛋白表达的变化和意义。方法:SP免疫组化法检测60例结直肠癌组织和癌旁正常组织Pokemon和c-myc蛋白的表达情况。结果:结直肠癌组织Pokemon和c-myc蛋白的阳性表达率均明显高于正常组织(P<0.01);结直肠癌组织Pokemon和c-myc蛋白的阳性表达与分化程度、Dukes分期和淋巴结转移有关(P<0.01,P<0.05);结直肠癌组织中,Pokemon和c-myc蛋白的表达呈显著正相关(r=0.615,P<0.05)。结论:Pokemon和c-myc对结直肠癌的诊断和预后评判具有一定的价值。%Objective: To investigate the expression and clinical significance of Pokemon and c-myc in human colorectal cancer.Methods: SP immunohistochemical staining was used to detect the expression of Pokemon and c-myc in 60 cases colorectal cancer and matched para-carcinoma tissues.Results:The positive expression rate of Pokemon and c-myc in colorectal cancer were obviously higher than that in normal tissue (P<0.01). In colorectal cancer, the positive expression of Pokemon and c-myc were related with differentiation degree, Dukes stage and lymph node metastasis (P<0.01,P<0.05). The positive expression of Pokemon in colorectal cancer was positively correlated with c-myc expression (r=0.615,P<0.05). Conclusions: Pokemon and c-myc have certain value for diagnosing and prognosis of colorectal cancer.

  14. Effect of Qi-protecting powder (Huqi San) on expression of c-jun, c-fos and c-myc in diethylnitrosamine-mediated hepatocarcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Xia Li; Zheng-Ming Shi; Ping Feng; Zhao-Yang Wen; Xue-Jiang Wang

    2007-01-01

    AIM: To study the inhibitory effect of Huqi San (Qiprotecting powder) on rat prehepatocarcinoma induced by diethylinitrosamine (DEN) by analyzing the mutational activation of c-fos proto-oncogene and over-expression of c-jun and c-myc oncogenes.METHODS: A Solt-Farber two-step test model of prehepatocarcinoma was induced in rats by DEN and 2-acetylaminofluorene (AAF) to investigate the modifying effects of Huqi San on the expression of c-jun, c-fos and c-myc in DEN-mediated hepatocarcinogenesis. Huqi San was made of eight medicinal herbs containing glycoprival granules, in which each milliliter contains 0.38 g crude drugs. γ-glutamy-transpeptidase-isoenzyme (γ-GTase)was determined with histochemical methods. Level of 8-hydroxydeoxyguanosine (OHdG) formed in liver and c-jun, c-fos and c-myc proto-oncogenes were detected by immunohistochemical methods.RESULTS: The level of 8-OHdG, a mark of oxidative DNA damage, was significantly decreased in the liver of rats with prehepatocarcinoma induced by DEN who received 8 g/kg body weight or 4 g/kg body weight Huqi San before (1 wk) and after DEN exposure (4 wk). Huqi Santreated rats showed a significant decrease in number of γ-GT positive foci (P < 0.001, prevention group: 4.96 ±0.72 vs 29.46 ± 2.17; large dose therapeutic group: 7.53± 0.88 vs 29.46 ± 2.17). On the other hand, significant changes in expression of c-jun, c-fos and c-myc were found in Huqi San-treated rats.CONCLUSION: Activation of c-jun, c-fos and c-myc plays a crucial role in the pathogenesis of liver cancer.Huqi San can inhibit the over-expression of c-jun, c-fos and c-myc oncogenes and liver preneolastic lesionsinduced by DEN.

  15. Cytogenetic characterization and evaluation of c-MYC gene amplification in PG100, a new Brazilian gastric cancer cell line

    Directory of Open Access Journals (Sweden)

    H.F. Ribeiro

    2010-08-01

    Full Text Available Gastric cancer is the fourth most frequent type of cancer and the second cause of cancer mortality worldwide. The genetic alterations described so far for gastric carcinomas include amplifications and mutations of the c-ERBB2, KRAS, MET, TP53, and c-MYC genes. Chromosomal instability described for gastric cancer includes gains and losses of whole chromosomes or parts of them and these events might lead to oncogene overexpression, showing the need for a better understanding of the cytogenetic aspects of this neoplasia. Very few gastric carcinoma cell lines have been isolated. The establishment and characterization of the biological properties of gastric cancer cell lines is a powerful tool to gather information about the evolution of this malignancy, and also to test new therapeutic approaches. The present study characterized cytogenetically PG-100, the first commercially available gastric cancer cell line derived from a Brazilian patient who had a gastric adenocarcinoma, using GTG banding and fluorescent in situ hybridization to determine MYC amplification. Twenty metaphases were karyotyped; 19 (95% of them presented chromosome 8 trisomy, where the MYC gene is located, and 17 (85% presented a deletion in the 17p region, where the TP53 is located. These are common findings for gastric carcinomas, validating PG100 as an experimental model for this neoplasia. Eighty-six percent of 200 cells analyzed by fluorescent in situ hybridization presented MYC overexpression. Less frequent findings, such as 5p deletions and trisomy 16, open new perspectives for the study of this tumor.

  16. c-myc, not her-2/neu, can predict the prognosis of breast cancer patients: how novel, how accurate, and how significant?

    International Nuclear Information System (INIS)

    The predictive and prognostic implication of oncogene amplification in breast cancer has received great attention in the past two decades. her-2/neu and c-myc are two oncogenes that are frequently amplified and overexpressed in breast carcinomas. Despite the extensive data on these oncogenes, their prognostic and predictive impact on breast cancer patients remains controversial. Schlotter and colleagues have recently suggested that c-myc, and not her-2/neu, could predict the recurrence and mortality of patients with node-negative breast carcinomas. Regardless of the promising results, caution should be exercised in the interpretation of data from studies assessing gene amplification without in situ analysis. We address the novelty, accuracy and clinical significance of the study by Schlotter and colleagues

  17. A Comparative Docking Strategy to Identify Polyphenolic Derivatives as Promising Antineoplastic Binders of G-quadruplex DNA c-myc and bcl-2 Sequences.

    Science.gov (United States)

    Costa, Giosuè; Rocca, Roberta; Moraca, Federica; Talarico, Carmine; Romeo, Isabella; Ortuso, Francesco; Alcaro, Stefano; Artese, Anna

    2016-09-01

    Polyphenols are compounds ubiquitously expressed in plants and used for their multiple healthy effects in humans as anti-inflammatory, antimicrobial, antiviral, anticancer and immunomodulatory agents. Due to their ability to modulate the activity of multiple targets involved in carcinogenesis, polyphenols can be employed to inhibit the growth of cancer cells. Several studies reported their high affinity to different G-quadruplex DNA structures, including the oncogene promoters c-myc and bcl-2. In this work we applied a structure-based virtual screening approach in order to screen a database of polyphenolic derivatives and human metabolites against both c-myc and bcl-2 DNA G-quadruplex structures. A Delphinidine derivative was identified as the best "dual" candidate and, after molecular dynamics simulations, resulted able to well stabilize both receptors. PMID:27546043

  18. Mutations induced at the promoter region of the c-myc gene due to dual exposure to ionizing radiation and methyl nitroso urea

    International Nuclear Information System (INIS)

    Malignant tumors were arising from a sequence of events including mutation in proto-oncogenes and tumor suppressor genes.The accretion of these mutations is apparently facilitated by acquired or inherited defects inguardianmechanisms that maintain the integrity of the cellular genome. The proto-oncogene c-myc, which is frequently over expressed in tumors at the center of a transcription factor network, requlates cellular proliferation replicate potential, growth, differentiation and apoptosis. Expression of c-myc is down reglated during differentiation and is rapidly induced by a diverse catalog of mutagens including ionizing radiation and many alkylating agents. In the present study, the dual exposure to methyl nitroso urea(MNU) and ionizing radiation were assessed. These induced effects were assessed histopathologically and biochemically and were correlated at the molecular level by assessing single strand conformation polymorphism (SSCP)

  19. In vivo MRS assessment of altered fatty acyl unsaturation in liver tumor formation of a TGFα/c-myc transgenic mouse model*

    OpenAIRE

    Griffitts, J.; Tesiram, Y.; Reid, G. E.; Saunders, D; Floyd, R A; Towner, R. A.

    2009-01-01

    Current detection methods (computed tomography, ultrasound, and MRI) for hepatocarcinogenesis in humans rely on visual confirmation of neoplastic formations. A more effective early detection method is needed. Using in vivo magnetic resonance spectroscopy (MRS), we show that alterations in the integral ratios of the bis-allyl to vinyl hydrogen protons in unsaturated lipid fatty acyl groups correlate with the development of neoplastic formations in vivo in a TGFα/c-myc mouse hepatocellular carc...

  20. Assessment of the effect of betaine on p16 and c-myc DNA methylation and mRNA expression in a chemical induced rat liver cancer model

    Directory of Open Access Journals (Sweden)

    Ling Wen-hua

    2009-07-01

    Full Text Available Abstract Background The development and progression of liver cancer may involve abnormal changes in DNA methylation, which lead to the activation of certain proto-oncogenes, such as c-myc, as well as the inactivation of certain tumor suppressors, such as p16. Betaine, as an active methyl-donor, maintains normal DNA methylation patterns. However, there are few investigations on the protective effect of betaine in hepatocarcinogenesis. Methods Four groups of rats were given diethylinitrosamine (DEN and fed with AIN-93G diets supplemented with 0, 10, 20 or 40 g betaine/kg (model, 1%, 2%, and 4% betaine, respectively, while the control group, received no DEN, fed with AIN-93G diet. Eight or 15 weeks later, the expression of p16 and c-myc mRNA was examined by Real-time PCR (Q-PCR. The DNA methylation status within the p16 and c-myc promoter was analyzed using methylation-specific PCR. Results Compared with the model group, numbers and areas of glutathione S-transferase placental form (GST-p-positive foci were decreased in the livers of the rats treated with betaine (P . Although the frequency of p16 promoter methylation in livers of the four DEN-fed groups appeared to increase, there is no difference among these groups after 8 or 15 weeks (P > 0.05. Betaine supplementation attenuated the down-regulation of p16 and inhibited the up-regulation of c-myc induced by DEN in a dose-dependent manner (P P . Finally, enhanced antioxidative capacity (T-AOC was observed in both the 2% and 4% betaine groups. Conclusion Our data suggest that betaine attenuates DEN-induced damage in rat liver and reverses DEN-induced changes in mRNA levels.

  1. Cytotoxic effect of γ-sitosterol from Kejibeling (Strobilanthes crispus and its mechanism of action towards c-myc gene expression and apoptotic pathway

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    Susi Endrini

    2015-01-01

    Full Text Available Background: This study aimed to analyze the cytotoxicity effect of γ-sitosterol isolated from “Kejibeling” (Strobilanthes crispus, a medicinal plant, on several cancer cell lines. The mechanisms of the effects were studied through the expression of cancer-caused gene, c-myc and apoptotic pathways.Methods: This in vitro study was done using human colon cancer cell lines (Caco-2, liver cancer cell lines (HepG2, hormone-dependent breast cancer cell lines (MCF-7 and the normal liver cell lines (Chang Liver. The cytotoxic effect was measured through MTT assay and the potential cytotoxic value was calculated by determining the toxic concentration which may kill up to 50% of the total cell used (IC50. Meanwhile, the cytotoxic mechanism was studied by determining the effect of adding γ-sitosterol to the c-myc gene expression by reverse transciptase-polymerase chain reaction (RT-PCR. The effect of γ-sitosterol through apoptotic pathway was studied by using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay.Results: γ-sitosterol was cytotoxic against Caco-2, HepG2, and MCF-7 with IC50-values of 8.3, 21.8, and 28.8 μg/mL, respectively. There were no IC50-values obtained from this compound against Chang Liver cell line. This compound induced apotosis on Caco-2 and HepG2 cell lines and suppressed the c-myc genes expression in both cells.Conclusion: γ-sitosterol was cytotoxic against colon and liver cancer cell lines and the effect was mediated by down-regulation of c-myc expression and induction of the apoptotic pathways.

  2. Growth inhibition and apoptosis induced by daunomycin-conjugated triplex-forming oligonucleotides targeting the c-myc gene in prostate cancer cells

    OpenAIRE

    Napoli, Sara; Negri, Umberto; Arcamone, Federico; Capobianco, Massimo L.; Giuseppina M. Carbone; Catapano, Carlo V

    2006-01-01

    Covalent attachment of intercalating agents to triplex-forming oligonucleotides (TFOs) is a promising strategy to enhance triplex stability and biological activity. We have explored the possibility to use the anticancer drug daunomycin as triplex stabilizing agent. Daunomycin-conjugated TFOs (dauno-TFOs) bind with high affinity and maintain the sequence-specificity required for targeting individual genes in the human genome. Here, we examined the effects of two dauno-TFOs targeting the c-myc ...

  3. Triplex-forming oligonucleotides targeting c-MYC potentiate the anti-tumor activity of gemcitabine in a mouse model of human cancer

    OpenAIRE

    Boulware, Stephen B.; Christensen, Laura A.; Thames, Howard; Coghlan, Lezlee; Vasquez, Karen M.; Finch, Rick A.

    2013-01-01

    Antimetabolite chemotherapy remains an essential cancer treatment modality, but often produces only marginal benefit due to the lack of tumor specificity, the development of drug resistance, and the refractoriness of slowly-proliferating cells in solid tumors. Here, we report a novel strategy to circumvent the proliferation-dependence of traditional antimetabolite-based therapies. Triplex-forming oligonucleotides (TFOs) were used to target site-specific DNA damage to the human c-MYC oncogene,...

  4. SirT1 knockdown potentiates radiation-induced bystander effect through promoting c-Myc activity and thus facilitating ROS accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Yuexia [Institute of Radiation Medicine, Fudan University, Shanghai (China); Central Laboratory, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China); Tu, Wenzhi; Zhang, Jianghong; He, Mingyuan; Ye, Shuang; Dong, Chen [Institute of Radiation Medicine, Fudan University, Shanghai (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, Shanghai (China)

    2015-02-15

    Highlights: • γ-Irradiation induced bystander effects between hepatoma cells and hepatocyte cells. • SirT1 played a protective role in regulating this bystander effect. • SirT1 contributed to the protective effects via elimination the accumulation of ROS. • The activity of c-Myc is critical for maintaining the protective role of SirT1. - Abstract: Radiation-induced bystander effect (RIBE) has important implications for secondary cancer risk assessment during cancer radiotherapy, but the bystander signaling processes, especially under hypoxic condition, are still largely unclear. The present study found that micronuclei (MN) formation could be induced in the non-irradiated HL-7702 hepatocyte cells after being treated with the conditioned medium from irradiated hepatoma HepG2 and SK-Hep-1 cells under either normoxia or hypoxia. This bystander response was dramatically diminished or enhanced when the SirT1 gene of irradiated hepatoma cells was overexpressed or knocked down, respectively, especially under hypoxia. Meanwhile, SirT1 knockdown promoted transcriptional activity for c-Myc and facilitated ROS accumulation. But both of the increased bystander responses and ROS generation due to SirT1-knockdown were almost completely suppressed by c-Myc interference. Moreover, ROS scavenger effectively abolished the RIBE triggered by irradiated hepatoma cells even with SirT1 depletion. These findings provide new insights that SirT1 has a profound role in regulating RIBE where a c-Myc-dependent release of ROS may be involved.

  5. A novel rapid-onset high-penetrance plasmacytoma mouse model driven by deregulation of cMYC cooperating with KRAS12V in BALB/c mice

    International Nuclear Information System (INIS)

    Our goal is to develop a rapid and scalable system for functionally evaluating deregulated genes in multiple myeloma (MM). Here, we forcibly expressed human cMYC and KRAS12V in mouse T2 B cells (IgM+B220+CD38+IgD+) using retroviral transduction and transplanted these cells into lethally irradiated recipient mice. Recipients developed plasmacytomas with short onset (70 days) and high penetrance, whereas neither cMYC nor KRAS12V alone induced disease in recipient mice. Tumor cell morphology and cell surface biomarkers (CD138+B220−IgM−GFP+) indicate a plasma cell neoplasm. Gene set enrichment analysis further confirms that the tumor cells have a plasma cell gene expression signature. Plasmacytoma cells infiltrated multiple loci in the bone marrow, spleen and liver; secreted immunoglobulins; and caused glomerular damage. Our findings therefore demonstrate that deregulated expression of cMYC with KRAS12V in T2 B cells rapidly generates a plasma cell disease in mice, suggesting utility of this model both to elucidate molecular pathogenesis and to validate novel targeted therapies

  6. A Novel PTEN/Mutant p53/c-Myc/Bcl-XL Axis Mediates Context-Dependent Oncogenic Effects of PTEN with Implications for Cancer Prognosis and Therapy

    Directory of Open Access Journals (Sweden)

    Xiaoping Huang

    2013-08-01

    Full Text Available Phosphatase and tensin homolog located on chromosome 10 (PTEN is one of the most frequently mutated tumor suppressors in human cancer including in glioblastoma. Here, we show that PTEN exerts unconventional oncogenic effects in glioblastoma through a novel PTEN/mutant p53/c-Myc/Bcl-XL molecular and functional axis. Using a wide array of molecular, genetic, and functional approaches, we demonstrate that PTEN enhances a transcriptional complex containing gain-of-function mutant p53, CBP, and NFY in human glioblastoma cells and tumor tissues. The mutant p53/CBP/NFY complex transcriptionally activates the oncogenes c-Myc and Bcl-XL, leading to increased cell proliferation, survival, invasion, and clonogenicity. Disruption of the mutant p53/c-Myc/Bcl-XL axis or mutant p53/CBP/NFY complex reverses the transcriptional and oncogenic effects of PTEN and unmasks its tumor-suppressive function. Consistent with these data, we find that PTEN expression is associated with worse patient survival than PTEN loss in tumors harboring mutant p53 and that a small molecule modulator of p53 exerts greater antitumor effects in PTEN-expressing cancer cells. Altogether, our study describes a new signaling pathway that mediates context-dependent oncogenic/tumor-suppressive role of PTEN. The data also indicate that the combined mutational status of PTEN and p53 influences cancer prognosis and anticancer therapies that target PTEN and p53.

  7. Induction of C-FOS, C-MYC and P53 by US -adrenergic receptor (US -AR) stimulation of rat parotid acinar cells (RPAC)

    Energy Technology Data Exchange (ETDEWEB)

    Kousvelari, E.E.; Louis, J.; Curran, T.; Baum, B.J.

    1987-05-01

    Treatment of rats with the US -agonist isoproterenol (ISO) results in dramatically increased parotid gland protein synthesis, processing and cell proliferation. The authors have shown that in RPAC in vitro, US -AR stimulation has similar effect on protein synthesis and processing. Proto-oncogenes have been implicated in growth regulation, differentiation and in mediating some extracellular stimulated events at the level of gene expression. To understand the regulation of cellular events after US -AR stimulation, the expression of c-fos, c-myc and p53 was investigated. RPAC were incubated with or without 10 VM ISO for 15, 30, 60 min. mRNA was isolated from cells and hybridization analysis was performed on nitrocellulose paper-transferred mRNA using TSP-labeled DNA probes. At early time points, the levels of c-fos gene activation in ISO-treated and control cells were comparable. After 60 min of ISO treatment, a sharp 20-30 fold induction of c-fos expression occurred. Similar increases in c-myc and p53 gene expression were observed after 60 min of ISO treatment. The authors data indicate that early effects of US -AR stimulation of RPAC include induction of c-fos, c-myc and p53 gene expression as well as enhanced protein synthesis and processing.

  8. Susceptibility of striatal neurons to excitotoxic injury correlates with basal levels of Bcl-2 and the induction of P53 and c-Myc immunoreactivity.

    Science.gov (United States)

    Liang, Zhong-Qin; Wang, Xiao-Xia; Wang, Yumei; Chuang, De-Maw; DiFiglia, Marian; Chase, Thomas N; Qin, Zheng-Hong

    2005-11-01

    The present studies evaluated the potential contribution of Bcl-2, p53, and c-Myc to the differential vulnerability of striatal neurons to the excitotoxin quinolinic acid (QA). In normal rat striatum, Bcl-2 immunoreactivity (Bcl-2-i) was most intense in large aspiny interneurons including choline acetyltransferase positive (CAT+) and parvalbumin positive (PARV+) neurons, but low in a majority of medium-sized neurons. In human brain, intense Bcl-2-i was seen in large striatal neurons but not in medium-sized spiny projection neurons. QA produced degeneration of numerous medium-sized neurons, but not those enriched in Bcl-2-i. Many Bcl-2-i-enriched interneurons including those with CAT+ and PARV+ survived QA injection, while medium-sized neurons labeled for calbindin D-28K (CAL D-28+) did not. In addition, proapoptotic proteins p53-i and c-Myc-i were robustly induced in medium-sized neurons, but not in most large neurons. The selective vulnerability of striatal medium spiny neurons to degeneration in a rodent model of Huntington's disease appears to correlate with their low levels of Bcl-2-i and high levels of induced p53-i and c-Myc-i. PMID:15922606

  9. Abrupt reduction of c-myc expression by antisense RNA inducing terminal differentiation and apoptosis of a human esophageal cancer cell line

    Institute of Scientific and Technical Information of China (English)

    赵晓航; 王秀琴; 周传农; 彭仁玲; 阎水中; 吴旻

    1995-01-01

    A human esophageal cancer cell line (EC8712) expressing high-level Myc protein was infected with recombmant retroviral particles (pA-BD9) at a multiplicity of infection (MOI) 1:1. This viral particle contains a neomycin-resistant gene and a 1.53-kb antisense RNA spanning the 2nd exon and its flanking sequences of the human c-myc oncogene. The G418-resistant EC8712 clones showed an 86% inhibition of growth rate and morphological changes characteristic of terminal differentiation and apoptosis. A decrease of about 80% of Myc protein was also observed in these infected cells by ABC-ELISA assay. 12-24 h after the infection of ECS712 cells with pA-BD9 at a high viral particle concentration (MOI = 1:10), the integration of the extrinsic 1.53-kb antisense c-myc fragment into the cancer cell genome was evidenced by the Southern blot analysis. Northern blot analyses showed the expression of this antisense fragment and a decrease of the intrinsic c-myc expression by 74% in comparison with that of the parental EC8

  10. INCREASED EXPRESSION OF PDGF AND C-MYC GENES IN LUNGS AND PULMONARY ARTERIES OF PULMONARY HYPERTENSIVE RATS INDUCED BY HYPOXIA

    Institute of Scientific and Technical Information of China (English)

    蔡英年; 韩梅; 罗兰; 宋为; 周晓梅

    1996-01-01

    The role of growth factors and proto-oncogene in pulmonary vascular structural remodelling is not well known.The present study examined gene expression of plateler-derived growth factor(PDGF)-A and -B chain and proto-oncogene,c-myc,in lung tissue and pulmonary artery of rats exposed to hypoxia and compred to those levels of gene expression in normal rats.Normal lungs and pulmonary artery expressed PDGF-A chain transcripr of 1.7kb and PDGF-B chain transcript of 3.5 Kb. The c-myc transcript of 2.2 kb was expressed as well.After hypoxic exposure for 7 and 14 days mRNA levels of PDGF-B chain and c-myc were elevated significantly compared with those of control rats.PDGF-A chain mRNA increased after hypoxia for 7 days,and then declined.These results suggest that activation of sutocrine and /or paracrine is important in proliferation mechanism of pulmonary artery smooth muscle cells in bypoxic pulmonary hypertensive rats.

  11. The Dysregulation of Polyamine Metabolism in Colorectal Cancer Is Associated with Overexpression of c-Myc and C/EBPβ rather than Enterotoxigenic Bacteroides fragilis Infection

    Directory of Open Access Journals (Sweden)

    Anastasiya V. Snezhkina

    2016-01-01

    Full Text Available Colorectal cancer is one of the most common cancers in the world. It is well known that the chronic inflammation can promote the progression of colorectal cancer (CRC. Recently, a number of studies revealed a potential association between colorectal inflammation, cancer progression, and infection caused by enterotoxigenic Bacteroides fragilis (ETBF. Bacterial enterotoxin activates spermine oxidase (SMO, which produces spermidine and H2O2 as byproducts of polyamine catabolism, which, in turn, enhances inflammation and tissue injury. Using qPCR analysis, we estimated the expression of SMOX gene and ETBF colonization in CRC patients. We found no statistically significant associations between them. Then we selected genes involved in polyamine metabolism, metabolic reprogramming, and inflammation regulation and estimated their expression in CRC. We observed overexpression of SMOX, ODC1, SRM, SMS, MTAP, c-Myc, C/EBPβ (CREBP, and other genes. We found that two mediators of metabolic reprogramming, inflammation, and cell proliferation c-Myc and C/EBPβ may serve as regulators of polyamine metabolism genes (SMOX, AZIN1, MTAP, SRM, ODC1, AMD1, and AGMAT as they are overexpressed in tumors, have binding site according to ENCODE ChIP-Seq data, and demonstrate strong coexpression with their targets. Thus, increased polyamine metabolism in CRC could be driven by c-Myc and C/EBPβ rather than ETBF infection.

  12. 艾灸对实验性类风湿关节炎滑膜细胞原癌基因 c-fos和c-myc mRNA表达的影响%Effects of moxibustion on the expression of protooncogene c-fos and c-myc mRNA in experimental arthritis

    Institute of Scientific and Technical Information of China (English)

    余俊辉; 刘旭光; 余曙光; 蔡美英; 周昌华; 赵宗蓉; 张平

    2005-01-01

    目的观察艾灸对实验性类风湿关节炎滑膜细胞原癌基因c-fos、c-myc mRNA表达的影响,初步探讨艾灸对RA滑膜细胞内分子信号传导的调控.方法在日本大耳白兔右后足踝关节部皮内注射福氏完全佐剂造模,经过艾灸治疗,通过半定量RT-PCR测定c-fos和c-myc mRNA的表达量.结果治疗组c-fos和c-myc mRNA表达量显著低于造模组(P<0.01).结论艾灸治疗能够降低c-fos和c-myc mRNA的表达,影响生长因子信号传导系统.

  13. C-MYC and BCL2 translocation frequency in diffuse large B-cell lymphomas: A study of 97 patients

    Directory of Open Access Journals (Sweden)

    Bahar Akkaya

    2016-01-01

    Full Text Available Purpose: Diffuse large B-cell lymphoma (DLBCL is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. MYC and BCL2 rearrangements have been reported in a proportion of DLBCLs, where they may be associated with an adverse clinical outcome. The aim of this study was to determine the frequency of MYC and BCL2 translocations in DLBCL and assess the prognostic impact in DLBCL patients. Materials and Methods:   In the present study, we evaluated the expression patterns of CD 10, BCL6, and MUM 1 by immunohistochemistry in 121 cases with DLBCL in tissue microarray (TMA: 62 cases in germinal center B-cells (GCBs; and 59 cases in activated B-cells (ABCs of which 60 were females and 61 were males. MYC and BCL2 rearrangements were investigated by interphase fluorescence in situ hybridization on TMAs in 97 DLBCLs. Result: MYC rearrangements were observed in 11 of 97 cases. There was no association with other clinical features, including age, sex, and nodal/extranodal disease. MYC rearrangement was associated with significantly worse overall survival (P < 0.01. BCL2 rearrangements were observed in 14 of 97 cases. There was no association with other clinical features including age and sex. BCL2 rearrangement had a worse outcome (P < 0.01. MYC and BCL2 rearrangements were observed in 3 of 97 cases with the age of  53 (female, 53, 63 years old, respectively, died in 24, 18, and 35 months after the diagnosis. Two cases had primary nodal and one case primary extranodal presentations. All these patients had stage IV disease. Conclusion: We concluded that C-MYC and BCL2 may contribute to aggressive transformation, and more mechanism-based therapy should be explored. Targeted therapies involving these rearrangements and its associated pathways may change the fate of DLBCLs. Analysis of MYC gene rearrangement along with BCL2 is critical in the identification of high-risk patients with poor prognosis.

  14. Establishment of c-myc-immortalized Kupffer cell line from a C57BL/6 mouse strain

    Directory of Open Access Journals (Sweden)

    Hiroshi Kitani

    2014-01-01

    Full Text Available We recently demonstrated in several mammalian species, a novel procedure to obtain liver-macrophages (Kupffer cells in sufficient numbers and purity using a mixed primary culture of hepatocytes. In this study, we applied this method to the C57BL/6 mouse liver and established an immortalized Kupffer cell line from this mouse strain. The hepatocytes from the C57BL/6 adult mouse liver were isolated by a two-step collagenase perfusion method and cultured in T25 culture flasks. Similar to our previous studies, the mouse hepatocytes progressively changed their morphology into a fibroblastic appearance after a few days of culture. After 7–10 days of culture, Kupffer-like cells, which were contaminants in the hepatocyte fraction at the start of the culture, actively proliferated on the mixed fibroblastic cell sheet. At this stage, a retroviral vector containing the human c-myc oncogene and neomycin resistance gene was introduced into the mixed culture. Gentle shaking of the culture flask, followed by the transfer and brief incubation of the culture supernatant, resulted in a quick and selective adhesion of Kupffer cells to a plastic dish surface. After selection with G418 and cloning by limiting dilutions, a clonal cell line (KUP5 was established. KUP5 cells displayed typical macrophage morphology and were stably passaged at 4–5 days intervals for more than 5 months, with a population doubling time of 19 h. KUP5 cells are immunocytochemically positive for mouse macrophage markers, such as Mac-1, F4/80. KUP5 cells exhibited substantial phagocytosis of polystyrene microbeads and the release of inflammatory cytokines upon lipopolysaccharide stimulation. Taken together, KUP5 cells provide a useful means to study the function of Kupffer cells in vitro.

  15. Nodal diffuse large B-cell lymphomas in children and adolescents: immunohistochemical expression patterns and c-MYC translocation in relation to clinical outcome.

    Science.gov (United States)

    Gualco, Gabriela; Weiss, Lawrence M; Harrington, William J; Bacchi, Carlos E

    2009-12-01

    Diffuse large B-cell lymphoma (DLBCL) is a very infrequent neoplasm in the pediatric age group; therefore there are very few studies on the immunophenotype or genetics of these cases. We studied a series of 16 patients with nodal DLBCL occurring in patients between 10 and 18 years of age. The cases were classified according to the 2008 World Health Organization classification criteria, with application of immunohistochemistry for the detection of CD10, BCL-6, and MUM1 proteins to divide the lymphomas into germinal center and nongerminal center types. In addition, TCL1, BCL-2 expression, and the Ki-67 proliferation index were evaluated by immunohistochemistry, and c-MYC and BCL2 translocations were evaluated by fluorescence in situ hybridization. All these parameters were correlated with clinical features and outcome. Our study revealed that centroblastic morphology and the germinal center type of DLBCL are more prevalent in these young patients (63%), with 37% containing a c-MYC translocation. Only 1 case showed a BCL2 translocation, reflecting a double-hit case with features intermediate between DLBCL and Burkitt lymphoma. We found a higher frequency of BCL-2 expression than previously reported, with no direct influence on the outcome of the disease in univariate or multivariate analysis. The expression of TCL1 has not been specifically studied in nodal pediatric DLBCL before; we found a 31% incidence of TCL1 expression. MUM1 expression was observed in 44% of the cases and these positive cases showed a significant negative impact on clinical outcome. TCL1 is directly and significantly associated with the presence of c-MYC and a high proliferative index. The germinal center and nongerminal center subtypes showed significant differences for both overall survival and disease-free interval. c-MYC translocation was found in 37% of patients, and had a favorable impact on clinical outcome. We conclude that nodal pediatric and adolescent DLBCL are mainly of the germinal

  16. 氧化苦参碱对结肠癌LoVo细胞c-myc,PSMD9,CDK4mRNA表达的影响%Effect of Oxymatrine on Expression of c-myc, PSMD9 and CDK4 mRNA in Human Colon Carcinoma LoVo Cells

    Institute of Scientific and Technical Information of China (English)

    彭燕; 韩凌; 孙静; 危建安

    2012-01-01

    目的:探讨氧化苦参碱( oxymatrine,OM)抑制人结肠癌LoVo细胞增殖和诱导凋亡的分子作用机制.方法:采用流式细胞仪检测LoVo细胞凋亡率以及细胞周期分布;采用荧光定量PCR法检测0.25,0.5 g·L-1 OM对LoVo细胞增殖相关基因c -myc,蛋白酶调解因子9(PSMD9),CDK4的基因表达的影响.结果:0.5 g·L-1以下浓度的OM作用结肠癌LoVo细胞48 h,对细胞凋亡无明显影响.0.25 g·L-1 OM作用48 h时可明显抑制人结肠癌LoVo细胞c-myc基因表达(P<0.05).0.5g·L-1 OM作用48 h时可明显抑制LoVo细胞c-myc,CDK4的基因表达(P <0.01,P<0.01,).药物作用时间为96 h时,0.5g·L-1 OM可明显抑制c-myc,PSM D9,CDK4基因表达(P<0.05,或P<0.01).结论:较低剂量OM显著抑制人结肠癌LoVo细胞增殖的作用机制,可能与下调LoVo细胞c-myc,PSM D9,CDK4表达有关.%Objective: To explore the molecular mechanism of inhibiting colon cancer cell strein LoVo proliferation and inducing apoptosis by oxymatrine ( OM ) Method: Flow cytometry was used to detect the LoVo cells apoptosis and cell cycle distribution. Fluorescence quantitative PCR was used to detect cell proliferation-related genes like the c-myc, proteasome modulator 9 (PSMD9) , CDK4 gene expression when LoVo was treated with 0. 25, 0. 5 g · L-1OM. Result: OM had no significant effect on apoptosis in colon cancer LoVo cells when the treatment of OM lasted 48 h and the concentration was lower than 0.5, 0.25 g · L-1 OM can inhibit c-myc gene expression in LoVo when duration of action last 24 h ( P < 0. 05 ). When the dose increated to 0. 5 g · L-1 and duration of action was 48 h, OM could inhibit c-myc, CDK4 gene expression in LoVo cells (P <0. 01 , P < 0. 01). When duration of action was extended to 96 h, 0. 5 g · L-1 OM could inhibit the c-myc, PSMD9, CDK4 gene expression in LoVo cells ( P < 0. 05, P < 0. 01, P < 0. 01 ). Conclusion; OM at Lower dose could significantly inhibit the proliferation of human colon cancer Lo

  17. C-Myc Induced Compensated Cardiac Hypertrophy Increases Free Fatty Acid Utilization for the Citric Acid Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Aaron; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O' Kelly-Priddy, Colleen M.; Isern, Nancy G.; Portman, Michael A.

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc-induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam). Isolated working hearts and 13Carbon (13C )-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing 13C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was confirmed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contribution in NTG. Substrate utilization was not significantly altered in 3dMyc versus cont. The free fatty acid FC was significantly greater in 7dMyc vs cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the mechanisms whereby this change maintained

  18. C-Myc induced compensated cardiac hypertrophy increases free fatty acid utilization for the citric acid cycle.

    Science.gov (United States)

    Olson, Aaron K; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O'Kelly Priddy, Colleen; Isern, Nancy; Portman, Michael A

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam) injections. Isolated working hearts and (13)Carbon ((13)C)-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing (13)C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (Cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was assessed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contributions in NTG. Substrate utilization was not significantly altered in 3dMyc versus Cont. The free fatty acid FC was significantly greater in 7dMyc versus Cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to Cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes for the citric acid cycle did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the

  19. Erlotinib-Cisplatin Combination Inhibits Growth and Angiogenesis through c-MYC and HIF-1α in EGFR-Mutated Lung Cancer In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Jasmine G. Lee

    2015-02-01

    Full Text Available Combination treatment for non–small cell lung cancer (NSCLC is becoming more popular due to the anticipation that it may be more effective than single drug treatment. In addition, there are efforts to genetically screen patients for specific mutations in light of attempting to administer specific anticancer agents that are most effective. In this study, we evaluate the anticancer and anti-angiogenic effects of low dose erlotinib-cisplatin combination in NSCLC in vitro and in vivo. In NSCLC cells harboring epidermal growth factor receptor (EGFR mutations, combination erlotinib-cisplatin treatment led to synergistic cell death, but there was minimal efficacy in NSCLC cells with wild-type EGFR. In xenograft models, combination treatment also demonstrated greater inhibition of tumor growth compared to individual treatment. The anti-tumor effect observed was secondary to the targeting of angiogenesis, evidenced by decreased vascular endothelial growth factor (VEGF levels and decreased levels of CD31 and microvessel density. Combination treatment targets angiogenesis through down-regulation of the c-MYC/hypoxia inducible factor 1-alpha (HIF-1α pathway. In fact, cell lines with EGFR exon 19 deletions expressed high basal levels of c-MYC and HIF-1α and correlate with robust responses to combination treatment. These results suggest that low dose erlotinib-cisplatin combination exhibits its anti-tumor activity by targeting angiogenesis through the modulation of the c-MYC/HIF-1α/VEGF pathway in NSCLC with EGFR exon 19 deletions. These findings may have significant clinical implications in patients with tumors harboring EGFR exon 19 deletions as they may be particularly sensitive to this regimen.

  20. Liver tumor formation by a mutant retinoblastoma protein in the transgenic mice is caused by an upregulation of c-Myc target genes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bo; Hikosaka, Keisuke; Sultana, Nishat; Sharkar, Mohammad Tofael Kabir [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Noritake, Hidenao [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Kimura, Wataru; Wu, Yi-Xin [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Kobayashi, Yoshimasa [Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Uezato, Tadayoshi [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan); Miura, Naoyuki, E-mail: nmiura@hama-med.ac.jp [Department of Biochemistry, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Fifty percent of the mutant Rb transgenic mice produced liver tumors. Black-Right-Pointing-Pointer In the tumor, Foxm1, Skp2, Bmi1 and AP-1 mRNAs were up-regulated. Black-Right-Pointing-Pointer No increase in expression of the Myc-target genes was observed in the non-tumorous liver. Black-Right-Pointing-Pointer Tumor formation depends on up-regulation of the Myc-target genes. -- Abstract: The retinoblastoma (Rb) tumor suppressor encodes a nuclear phosphoprotein that regulates cellular proliferation, apoptosis and differentiation. In order to adapt itself to these biological functions, Rb is subjected to modification cycle, phosphorylation and dephosphorylation. To directly determine the effect of phosphorylation-resistant Rb on liver development and function, we generated transgenic mice expressing phosphorylation-resistant human mutant Rb (mt-Rb) under the control of the rat hepatocyte nuclear factor-1 gene promoter/enhancer. Expression of mt-Rb in the liver resulted in macroscopic neoplastic nodules (adenomas) with {approx}50% incidence within 15 months old. Interestingly, quantitative reverse transcriptase-PCR analysis showed that c-Myc was up-regulated in the liver of mt-Rb transgenic mice irrespective of having tumor tissues or no tumor. In tumor tissues, several c-Myc target genes, Foxm1, c-Jun, c-Fos, Bmi1 and Skp2, were also up-regulated dramatically. We determined whether mt-Rb activated the Myc promoter in the HTP9 cells and demonstrated that mt-Rb acted as an inhibitor of wild-type Rb-induced repression on the Myc promoter. Our results suggest that continued upregulation of c-Myc target genes promotes the liver tumor formation after about 1 year of age.

  1. AID induces double-strand breaks at immunoglobulin switch regions and c-MYC causing chromosomal translocations in yeast THO mutants.

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    José F Ruiz

    2011-02-01

    Full Text Available Transcription of the switch (S regions of immunoglobulin genes in B cells generates stable R-loops that are targeted by Activation Induced Cytidine Deaminase (AID, triggering class switch recombination (CSR, as well as translocations with c-MYC responsible for Burkitt's lymphomas. In Saccharomyces cerevisiae, stable R-loops are formed co-transcriptionally in mutants of THO, a conserved nuclear complex involved in mRNP biogenesis. Such R-loops trigger genome instability and facilitate deamination by human AID. To understand the mechanisms that generate genome instability mediated by mRNP biogenesis impairment and by AID, we devised a yeast chromosomal system based on different segments of mammalian S regions and c-MYC for the analysis of chromosomal rearrangements in both wild-type and THO mutants. We demonstrate that AID acts in yeast at heterologous S and c-MYC transcribed sequences leading to double-strand breaks (DSBs which in turn cause chromosomal translocations via Non-Homologous End Joining (NHEJ. AID-induced translocations were strongly enhanced in yeast THO null mutants, consistent with the idea that AID-mediated DSBs depend on R-loop formation. Our study not only provides new clues to understand the role of mRNP biogenesis in preventing genome rearrangements and the mechanism of AID-mediated genome instability, but also shows that, once uracil residues are produced by AID-mediated deamination, these are processed into DSBs and chromosomal rearrangements by the general and conserved DNA repair functions present from yeast to human cells.

  2. Angiotensin II reduces cardiac AdipoR1 expression through AT1 receptor/ROS/ERK1/2/c-Myc pathway.

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    Li Li

    Full Text Available Adiponectin, an abundant adipose tissue-derived protein, exerts protective effect against cardiovascular disease. Adiponectin receptors (AdipoR1 and AdipoR2 mediate the beneficial effects of adiponectin on the cardiovascular system. However, the alteration of AdipoRs in cardiac remodeling is not fully elucidated. Here, we investigated the effect of angiotensin II (AngII on cardiac AdipoRs expression and explored the possible molecular mechanism. AngII infusion into rats induced cardiac hypertrophy, reduced AdipoR1 but not AdipoR2 expression, and attenuated the phosphorylations of adenosine monophosphate-activated protein kinase and acetyl coenzyme A carboxylase, and those effects were all reversed by losartan, an AngII type 1 (AT1 receptor blocker. AngII reduced expression of AdipoR1 mRNA and protein in cultured neonatal rat cardiomyocytes, which was abolished by losartan, but not by PD123319, an AT2 receptor antagonist. The antioxidants including reactive oxygen species (ROS scavenger NAC, NADPH oxidase inhibitor apocynin, Nox2 inhibitor peptide gp91 ds-tat, and mitochondrial electron transport chain complex I inhibitor rotenone attenuated AngII-induced production of ROS and phosphorylation of extracellular signal-regulated kinase (ERK 1/2. AngII-reduced AdipoR1 expression was reversed by pretreatment with NAC, apocynin, gp91 ds-tat, rotenone, and an ERK1/2 inhibitor PD98059. Chromatin immunoprecipitation assay demonstrated that AngII provoked the recruitment of c-Myc onto the promoter region of AdipoR1, which was attenuated by PD98059. Moreover, AngII-induced DNA binding activity of c-Myc was inhibited by losartan, NAC, apocynin, gp91 ds-tat, rotenone, and PD98059. c-Myc small interfering RNA abolished the inhibitory effect of AngII on AdipoR1 expression. Our results suggest that AngII inhibits cardiac AdipoR1 expression in vivo and in vitro and AT1 receptor/ROS/ERK1/2/c-Myc pathway is required for the downregulation of AdipoR1 induced by AngII.

  3. PET/CT Imaging of c-Myc Transgenic Mice Identifies the Genotoxic N-Nitroso-Diethylamine as Carcinogen in a Short-Term Cancer Bioassay

    OpenAIRE

    Katja Hueper; Mahmoud Elalfy; Florian Laenger; Roman Halter; Thomas Rodt; Michael Galanski; Juergen Borlak

    2012-01-01

    BACKGROUND: More than 100,000 chemicals are in use but have not been tested for their safety. To overcome limitations in the cancer bioassay several alternative testing strategies are explored. The inability to monitor non-invasively onset and progression of disease limits, however, the value of current testing strategies. Here, we report the application of in vivo imaging to a c-Myc transgenic mouse model of liver cancer for the development of a short-term cancer bioassay. METHODOLOGY/PRINCI...

  4. Effect of hydroxyapatite nanoparticles on the growth and p53/c-Myc protein expression of implanted hepatic VX2 tumor in rabbits by intravenous injection

    Institute of Scientific and Technical Information of China (English)

    Jun Hu; Zhi-Su Liu; Sheng-Li Tang; Yue-Ming He

    2007-01-01

    AIM:To evaluate the effect of hydroxyapatite nanoparticles (Nano HAP) by intravenous injection on the inhibition of implanted hepatic VX2 tumor growth in rabbits and cell p53/c-Myc protein expression.METHODS: 60 hepatic VX2 tumor-bearing rabbits was randomly divided into five groups. Nano HAP collosol 20 mg/kg, 40 mg/kg, 5-FU solutions 20 mg/mL, mixed liquor of 5-FU solution 20 mg/mL and Nano HAP collosol 20 mg/kg were infused by vein, normal saline conducted as the control. The general state, weight, liver function and gross tumor volume were detected dynamically.The expression of p53 and c-Myc gene protein in tumor tissue was detected by immunohistochemistry methods.RESULTS: The growth of implanted hepatic VX2 tumors was significantly inhibited in all therapy groups, 3 wk after the injection, the tumor control rates in Nano HAP collosol groups were 25.5% and 32.5% respectively,and the gross tumor volumes were obviously less than that of control group. (24.81 ± 5.17 and 22.73 ± 4.23vs 33.32 ± 5.26, P < 0.05). The tumor control rate of 5-FU group was 43.7% (18.74 ± 4.40 vs 33.32 ± 5.26,P < 0.05), but the general state of the animals after injection aggravated; and the adverse reaction in the drug combination group obviously decreased. Due to the effect of Nano HAP, the positive expression of tumor associated the mutated p53 and c-Myc in tumor tissue was decreased obviously compared with the control group.CONCLUSION: Nano HAP has evident inhibitory action on rabbit implanted hepatic VX2 tumor in vivo, which may be the result of decreasing the expression of the mutated p53 and c-myc, and drug combination can obviously decrease the adverse reaction of 5-FU.

  5. Wogonin has multiple anti-cancer effects by regulating c-Myc/SKP2/Fbw7α and HDAC1/HDAC2 pathways and inducing apoptosis in human lung adenocarcinoma cell line A549.

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    Xin-mei Chen

    Full Text Available Wogonin is a plant monoflavonoid which has been reported to inhibit cell growth and/or induce apoptosis in various tumors. The present study examined the apoptosis-inducing activity and underlying mechanism of action of wogonin in A549 cells. The results showed that wogonin was a potent inhibitor of the viability of A549 cells. Apoptotic protein changes detected after exposure to wogonin included decreased XIAP and Mcl-1 expression, increased cleaved-PARP expression and increased release of AIF and cytochrome C. Western blot analysis showed that the activity of c-Myc/Skp2 and HDAC1/HDAC2 pathways, which play important roles in tumor progress, was decreased. Quantitative PCR identified increased levels of c-Myc mRNA and decreased levels of its protein. Protein levels of Fbw7α, GSK3β and Thr58-Myc, which are involved in c-Myc ubiquitin-dependent degradation, were also analyzed. After exposure to wogonin, Fbw7α and GSK3β expression decreased and Thr58-Myc expression increased. However, MG132 was unable to prevent c-Myc degradation. The present results suggest that wogonin has multiple anti-cancer effects associated with degradation of c-Myc, SKP2, HDAC1 and HDAC2. Its ability to induce apoptosis independently of Fbw7α suggests a possible use in drug-resistance cancer related to Fbw7 deficiency. Further studies are needed to determine which pathways are related to c-Myc and Fbw7α reversal and whether Thr58 phosphorylation of c-Myc is dependent on GSK3β.

  6. 阴道脱落细胞检查联合人类染色体末端酶基因、c-myc 检测在宫颈癌诊断中的价值%The clinical value of Thinprep cytology test combined with h -TERC and c -myc in the diagnosis of cervical ;cancer

    Institute of Scientific and Technical Information of China (English)

    毛海波

    2015-01-01

    Objective To explore the clinical value of Thinprep cytology test (TCT)combined with h -TERC and c -myc in the diagnosis of cervical cancer.Methods hTERC amplification was detected by dual -color interphase fluorescence in situ hybridization (FISH),and the results were compared with TCT and histological examination.Examination the positive which TCT,h -TERC and c -myc by pathological examination.The final diag-nosis was determined by the pathological examination.Results TCT was abnormal in 26.4% of 500 case,18.0%abnormal h -TERC gene,16.0% abnormal c -myc gene.In 270 cases according to the cervical biopsy,the positive rate of chronic inflammation,cervical intraepithelial neoplasia (CIN)Ⅰ,CINⅡ,CINⅢ and cervical cancer:44.4%, 38.2%,36.4%,18.2%,and 7.3% respectively.The positive rates of h -TERC were 18.1%,45.4%,52.5%, 65.9% and 100.0%,respectively.The positive rates of c -myc were 21.4%,48.9%,56.7%,59.9% and 100.0%.With increased pathological grade,the expressions of h -TERC and c -myc were high.Conclusion TCT combined with h -TERC and c -myc can test cervical cancer more effective.%目的:探讨阴道脱落细胞检查(TCT)结合人类染色体末端酶基因(h-TERC)和 c-myc 检测在宫颈癌中的价值。方法运用免疫荧光原位杂交技术检测近三年来该院宫颈癌患者500例的宫颈脱落细胞中h-TERC 和 c-myc 的表达,将其检测结果与 TCT 检测结果比较,将上述三种结果的任一阳性检测再进行病理学诊断标准来确定,且以病理诊断为准进行分析。结果在所检测的500例患者中,TCT 异常者132例(26.4%),h-TECR 异常者90例(18.0%),c-myc 异常者80例(16.0%),将270例患者进行阴道宫颈活检技术,在这些病例中,宫颈慢性炎者120例,宫颈病变者150例,其中宫颈上皮瘤变 CINⅠ52例(38.2%),CINⅡ50例(36.4%),CIN Ⅲ30例(18.2%),宫颈癌18例(7.3%)。在所检测的病例中,

  7. NM23-H2 may play an indirect role in transcriptional activation of c-myc gene expression but does not cleave the nuclease hypersensitive element III[subscript 1

    Energy Technology Data Exchange (ETDEWEB)

    Dexheimer, Thomas S.; Carey, Steven S.; Zuohe, Song; Gokhale, Vijay M.; Hu, Xiaohui; Murata, Lauren B.; Maes, Estelle M.; Weichsel, Andrzej; Sun, Daekyu; Meuillet, Emmanuelle J.; Montfort, William R.; Hurley, Laurence H. (Ariz)

    2009-05-13

    The formation of G-quadruplex structures within the nuclease hypersensitive element (NHE) III{sub 1} region of the c-myc promoter and the ability of these structures to repress c-myc transcription have been well established. However, just how these extremely stable DNA secondary structures are transformed to activate c-myc transcription is still unknown. NM23-H2/nucleoside diphosphate kinase B has been recognized as an activator of c-myc transcription via interactions with the NHE III{sub 1} region of the c-myc gene promoter. Through the use of RNA interference, we confirmed the transcriptional regulatory role of NM23-H2. In addition, we find that further purification of NM23-H2 results in loss of the previously identified DNA strand cleavage activity, but retention of its DNA binding activity. NM23-H2 binds to both single-stranded guanine- and cytosine-rich strands of the c-myc NHE III{sub 1} and, to a lesser extent, to a random single-stranded DNA template. However, it does not bind to or cleave the NHE III{sub 1} in duplex form. Significantly, potassium ions and compounds that stabilize the G-quadruplex and i-motif structures have an inhibitory effect on NM23-H2 DNA-binding activity. Mutation of Arg{sup 88} to Ala{sup 88} (R88A) reduced both DNA and nucleotide binding but had minimal effect on the NM23-H2 crystal structure. On the basis of these data and molecular modeling studies, we have proposed a stepwise trapping-out of the NHE III{sub 1} region in a single-stranded form, thus allowing single-stranded transcription factors to bind and activate c-myc transcription. Furthermore, this model provides a rationale for how the stabilization of the G-quadruplex or i-motif structures formed within the c-myc gene promoter region can inhibit NM23-H2 from activating c-myc gene expression.

  8. Phospholipase D1 Couples CD4+ T Cell Activation to c-Myc-Dependent Deoxyribonucleotide Pool Expansion and HIV-1 Replication.

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    Harry E Taylor

    2015-05-01

    Full Text Available Quiescent CD4+ T cells restrict human immunodeficiency virus type 1 (HIV-1 infection at early steps of virus replication. Low levels of both deoxyribonucleotide triphosphates (dNTPs and the biosynthetic enzymes required for their de novo synthesis provide one barrier to infection. CD4+ T cell activation induces metabolic reprogramming that reverses this block and facilitates HIV-1 replication. Here, we show that phospholipase D1 (PLD1 links T cell activation signals to increased HIV-1 permissivity by triggering a c-Myc-dependent transcriptional program that coordinates glucose uptake and nucleotide biosynthesis. Decreasing PLD1 activity pharmacologically or by RNA interference diminished c-Myc-dependent expression during T cell activation at the RNA and protein levels. PLD1 inhibition of HIV-1 infection was partially rescued by adding exogenous deoxyribonucleosides that bypass the need for de novo dNTP synthesis. Moreover, the data indicate that low dNTP levels that impact HIV-1 restriction involve decreased synthesis, and not only increased catabolism of these nucleotides. These findings uncover a unique mechanism of action for PLD1 inhibitors and support their further development as part of a therapeutic combination for HIV-1 and other viral infections dependent on host nucleotide biosynthesis.

  9. Nuclear localization of vascular endothelial growth factor-D and regulation of c-Myc-dependent transcripts in human lung fibroblasts.

    Science.gov (United States)

    El-Chemaly, Souheil; Pacheco-Rodriguez, Gustavo; Malide, Daniela; Meza-Carmen, Victor; Kato, Jiro; Cui, Ye; Padilla, Philip I; Samidurai, Arun; Gochuico, Bernadette R; Moss, Joel

    2014-07-01

    Lymphangiogenesis and angiogenesis are processes that are, in part, regulated by vascular endothelial growth factor (VEGF)-D. The formation of lymphatic structures has been implicated in multiple lung diseases, including pulmonary fibrosis. VEGF-D is a secreted protein produced by fibroblasts and macrophages, which induces lymphangiogenesis by signaling via VEGF receptor-3, and angiogenesis through VEGF receptor-2. VEGF-D contains a central VEGF homology domain, which is the biologically active domain, with flanking N- and C-terminal propeptides. Full-length VEGF-D (∼ 50 kD) is proteolytically processed in the extracellular space, to generate VEGF homology domain that contains the VEGF-D receptor-binding sites. Here, we report that, independent of its cell surface receptors, full-length VEGF-D accumulated in nuclei of fibroblasts, and that this process appears to increase with cell density. In nuclei, full-length VEGF-D associated with RNA polymerase II and c-Myc. In cells depleted of VEGF-D, the transcriptionally regulated genes appear to be modulated by c-Myc. These findings have potential clinical implications, as VEGF-D was found in fibroblast nuclei in idiopathic pulmonary fibrosis, a disease characterized by fibroblast proliferation. These findings are consistent with actions of full-length VEGF-D in cellular homeostasis in health and disease, independent of its receptors.

  10. c-myc蛋白在不同毛色羊驼皮肤中的定位及表达%Localization and Expression of c-myc Protein in Different Colors of Alpaca Skin

    Institute of Scientific and Technical Information of China (English)

    张丹丽; 田雪; 董常生

    2013-01-01

    This experiment was conducted to explore the localization and expression of c-myc in different colors of alpaca skin.The tissues were obtained from white and brown adult alpacas' skins.The protein expression and the localization of c-myc were measured by immunohistochemistry.The positive signals of c-myc were found in hair bulb of hair follicle,and the comparative expression level of c-myc in brown alpacas was 5.51 times higher than that in white ones according to the average optical density analysis which indicated that c-myc may involve in the regulation of hair color formation.%为了探索c-myc蛋白在羊驼皮肤中的定位及表达情况,以不同毛色的成年羊驼为研究对象,采用免疫组织化学方法检测c-myc蛋白在羊驼皮肤组织中的表达和定位.结果显示,c-myc在羊驼皮肤毛囊毛球部细胞中呈阳性表达,根据光密度值分析得出c-myc在棕色羊驼毛囊中显著表达,其相对表达量是白色羊驼的5.51倍.研究表明c-myc可能参与羊驼毛色形成.

  11. ALK and c-myc gene of anaplastic large cell lymphoma%间变性大细胞淋巴瘤的ALK和c-myc基因研究

    Institute of Scientific and Technical Information of China (English)

    于冉; 周春菊; 陈刚; 高子芬; 时云飞; 石岩; 谢建兰; 周小鸽; 宫丽平

    2010-01-01

    目的 探讨间变性大细胞淋巴瘤(ALCL)中间变性淋巴瘤激酶(ALK)基因与c-myc基因的分子遗传学改变.方法 收集原发系统性ALCL石蜡包埋组织标本72例,利用间期荧光原位杂交(FISH)技术检测ALCL肿瘤组织中ALK和c-myc基因结构与数目的变化.结果 72例ALCL中,ALK阳性者42例,40例存在涉及ALK基因的染色体易位,其中17例同时伴有ALK基因的多拷贝;ALK阴性的30例均未发现ALK基因的易位,但其中14例存在ALK基因的多拷贝.ALK基因多拷贝的发生率在ALK阳性与阴性组中的差异无统计学意义(P>0.05).72例病例中,均未发现涉及c-myc基因的染色体易位,但其中24例存在c-myc基因的多拷贝.结论 大部分ALCL伴有ALK基因的异常(75.0%).以涉及ALK基因的染色体易位最为多见(55.6%),ALK基因多拷贝也是ALCL较为常见的遗传学改变(43.1%).前者只出现于ALK阳性ALCL中,后者既可出现在ALK阳性也可出现在ALK阴性的ALCL中.ALCL中不见或罕见涉及c-myc基因的染色体易位,但c-myc基因多拷贝的现象较为常见(33.3%).%Objective To investigate the molecular genetic changes of anaplastic lymphoma kinase (ALK) gene and c-myc gene in anaplastic large cell lymphoma (ALCL). Methods The structural aberrations and changes of copy numbers in ALK and c-myc genes in 72 paraffin-embedded ALCL specimens were detected by interphase fluorescence in situ hybridization (FISH). Results Among 72 ALCL specimens, ALK protein was expressed in 42, ALK gene translocation was detected in 40 specimens in which extra copies of ALK gene were detected in 17. ALK gene translocation was not found in all 30 ALK negative specimens, but extra copies of ALK gene were detected in 14 cases. The difference of incidence rates of extra copies in ALK gene between ALK positive and ALK negative specimens was not significant (P>0.05). c-myc gene translocation was not found in any of 72 ALCL specimens, but extra copies were detected in 24

  12. Expressão dos protooncogenes c-fos, c-myc e c-jun em miométrio normal e mioma humanos Expression of the protooncogenes c-fos, c-myc and c-jun in human normal miometrium and leiomyoma

    Directory of Open Access Journals (Sweden)

    Ana Luiza Ferrari

    2006-10-01

    Full Text Available OBJETIVO: Comparar a expressão gênica (mRNA e protéica dos protooncogenes c-fos, c-myc e c-jun em miométrio normal e mioma humanos. MÉTODOS: Foi realizado um estudo do tipo caso-controle. O material foi coletado de 12 pacientes submetidas a histerectomia no Hospital de Clínicas de Porto Alegre. A expressão do mRNA específico para c-myc, c-fos, c-jun e beta-microglobulina foi avaliada pela técnica de RT-PCR, utilizando primers específicos para cada gene. A expressão protéica destes protooncogenes foi avaliada através de Western blot com anticorpos específicos. RESULTADOS: Não houve diferença significativa para expressão gênica desses protooncogenes entre miométrio normal e mioma (c-myc: 0,87 ± 0,08 vs 0,87 ± 0,08, p = 0,952; c-fos: 1,10 ± 0,17 vs 1,01 ± 0,11, p = 0,21; c-jun: 1,03 ± 0,12 vs 0,96 ± 0,09, p = 0,168, respectivamente. Não houve diferença significativa para expressão protéica desses protooncogenes entre miométrio normal e mioma (c-myc: 1,36 ± 0,48 vs 1,53 ± 0,29, p = 0,569; c-fos: 8,85 ± 5,5 vs 6,56 ± 4,22, p = 0,434; e c-jun: 6,47 ± 3,04 vs 5,42 ± 2,03, p = 0,266, respectivamente. CONCLUSÃO: A expressão gênica (transcrição e a expressão protéica (tradução dos protooncogenes c-myc, c-fos e c-jun em mioma e miométrio normal são semelhantes.Uterine myomas are common benign tumors of the female genital tract. The expression of growth factor signal transduction cascade components including the protooncogenes c-myc, c-fos, and c-jun seem to be involved in the development of myomas. PURPOSE: To compare the gene (mRNA and protein expression of the protooncogenes c-fos, c-myc, and c-jun in human normal myometrium and leiomyoma. METHOD: A case-control study was performed. Samples were collected from 12 patients submitted to hysterectomy at the Hospital de Clínicas at Porto Alegre. The expression of the specific mRNA for c-myc, c-fos, c-jun, and beta-microglobulin was assessed through the RT

  13. c-Myc dependent expression of pro-apoptotic Bim renders HER2-overexpressing breast cancer cells dependent on anti-apoptotic Mcl-1

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    Jézéquel Pascal

    2011-09-01

    Full Text Available Abstract Background Anti-apoptotic signals induced downstream of HER2 are known to contribute to the resistance to current treatments of breast cancer cells that overexpress this member of the EGFR family. Whether or not some of these signals are also involved in tumor maintenance by counteracting constitutive death signals is much less understood. To address this, we investigated what role anti- and pro-apoptotic Bcl-2 family members, key regulators of cancer cell survival, might play in the viability of HER2 overexpressing breast cancer cells. Methods We used cell lines as an in vitro model of HER2-overexpressing cells in order to evaluate how anti-apoptotic Bcl-2, Bcl-xL and Mcl-1, and pro-apoptotic Puma and Bim impact on their survival, and to investigate how the constitutive expression of these proteins is regulated. Expression of the proteins of interest was confirmed using lysates from HER2-overexpressing tumors and through analysis of publicly available RNA expression data. Results We show that the depletion of Mcl-1 is sufficient to induce apoptosis in HER2-overexpressing breast cancer cells. This Mcl-1 dependence is due to Bim expression and it directly results from oncogenic signaling, as depletion of the oncoprotein c-Myc, which occupies regions of the Bim promoter as evaluated in ChIP assays, decreases Bim levels and mitigates Mcl-1 dependence. Consistently, a reduction of c-Myc expression by inhibition of mTORC1 activity abrogates occupancy of the Bim promoter by c-Myc, decreases Bim expression and promotes tolerance to Mcl-1 depletion. Western blot analysis confirms that naïve HER2-overexpressing tumors constitutively express detectable levels of Mcl-1 and Bim, while expression data hint on enrichment for Mcl-1 transcripts in these tumors. Conclusions This work establishes that, in HER2-overexpressing tumors, it is necessary, and maybe sufficient, to therapeutically impact on the Mcl-1/Bim balance for efficient induction of

  14. Combined loss of PUMA and p21 accelerates c-MYC-driven lymphoma development considerably less than loss of one allele of p53.

    Science.gov (United States)

    Valente, L J; Grabow, S; Vandenberg, C J; Strasser, A; Janic, A

    2016-07-21

    The tumor suppressor p53 is mutated in ~50% of human cancers. P53 is activated by a range of stimuli and regulates several cellular processes, including apoptotic cell death, cell cycle arrest, senescence and DNA repair. P53 induces apoptosis via transcriptional induction of the BH3-only proteins PUMA (p53-upregulated modulator of apoptosis) and NOXA, and cell cycle arrest via p21. Induction of these processes was proposed to be critical for p53-mediated tumor suppression. It is therefore surprising that mice lacking PUMA, NOXA and p21, as well as mice bearing mutations in p53 that impair the transcriptional activation of these genes, are not tumor prone, unlike mice lacking p53 function, which spontaneously develop tumors with 100% incidence. These p53 target genes and the processes they regulate may, however, impact differently on tumor development depending on the oncogenic drivers. For example, loss of PUMA enhances c-MYC-driven lymphoma development in mice, but, interestingly, the acceleration was less impressive compared with that caused by the loss of even a single p53 allele. Different studies have reported that loss of p21 can accelerate, delay or have no impact on tumorigenesis. In an attempt to resolve this controversy, we examined whether loss of p21-mediated cell cycle arrest cooperates with PUMA deficiency in accelerating lymphoma development in Eμ-Myc mice (overexpressing c-MYC in B-lymphoid cells). We found that Eμ-Myc mice lacking both p21 and PUMA (Eμ-Myc;Puma(-/-);p21(-/-)) developed lymphoma at a rate comparable to Eμ-Myc;Puma(-/-) animals, notably with considerably longer latency than Eμ-Myc;p53(+/-)mice. Loss of p21 had no impact on the numbers, cycling or survival of pre-leukemic Eμ-Myc B-lymphoid cells, even when PUMA was lost concomitantly. These results demonstrate that even in the context of deregulated c-MYC expression, p53 must suppress tumor development by activating processes apart from, or in addition to, PUMA

  15. Targeting human c-Myc promoter duplex DNA with actinomycin D by use of multi-way analysis of quantum-dot-mediated fluorescence resonance energy transfer

    DEFF Research Database (Denmark)

    Gholami, Somayeh; Kompany Zare, Mohsen

    2013-01-01

    investigated by use of 2D-photoluminescence emission (2D-PLE), and the resulting data were subjected to analysis by use of convenient and powerful multi-way approaches. Fluorescence measurements were performed by use of the quantum dot (QD)-conjugated c-Myc promoter. Intercalation of 7AAD within duplex base...... important advantage over univariate classical methods of enabling us to investigate the source of variance in the fluorescence signal of the DNA-drug complex. It was established that hard trilinear decomposition analysis of FRET-measured data overcomes the problem of rank deficiency, enabling calculation of...... hybridization stability 1.0 x 10(8) mol(-1) L obtained were in good agreement with values reported in the literature. The analytical concentration of the QD-labeled DNA was determined by use of nonlinear fitting, without using external standard calibration samples. This study was a successful application of...

  16. Protein kinase A antagonist inhibits β-catenin nuclear translocation, c-Myc and COX-2 expression and tumor promotion in ApcMin/+ mice

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    Brudvik Kristoffer W

    2011-12-01

    Full Text Available Abstract Background The adenomatous polyposis coli (APC protein is part of the destruction complex controlling proteosomal degradation of β-catenin and limiting its nuclear translocation, which is thought to play a gate-keeping role in colorectal cancer. The destruction complex is inhibited by Wnt-Frz and prostaglandin E2 (PGE2 - PI-3 kinase pathways. Recent reports show that PGE2-induced phosphorylation of β-catenin by protein kinase A (PKA increases nuclear translocation indicating two mechanisms of action of PGE2 on β-catenin homeostasis. Findings Treatment of ApcMin/+ mice that spontaneously develop intestinal adenomas with a PKA antagonist (Rp-8-Br-cAMPS selectively targeting only the latter pathway reduced tumor load, but not the number of adenomas. Immunohistochemical characterization of intestines from treated and control animals revealed that expression of β-catenin, β-catenin nuclear translocation and expression of the β-catenin target genes c-Myc and COX-2 were significantly down-regulated upon Rp-8-Br-cAMPS treatment. Parallel experiments in a human colon cancer cell line (HCT116 revealed that Rp-8-Br-cAMPS blocked PGE2-induced β-catenin phosphorylation and c-Myc upregulation. Conclusion Based on our findings we suggest that PGE2 act through PKA to promote β-catenin nuclear translocation and tumor development in ApcMin/+ mice in vivo, indicating that the direct regulatory effect of PKA on β-catenin nuclear translocation is operative in intestinal cancer.

  17. PET/CT imaging of c-Myc transgenic mice identifies the genotoxic N-nitroso-diethylamine as carcinogen in a short-term cancer bioassay.

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    Katja Hueper

    Full Text Available BACKGROUND: More than 100,000 chemicals are in use but have not been tested for their safety. To overcome limitations in the cancer bioassay several alternative testing strategies are explored. The inability to monitor non-invasively onset and progression of disease limits, however, the value of current testing strategies. Here, we report the application of in vivo imaging to a c-Myc transgenic mouse model of liver cancer for the development of a short-term cancer bioassay. METHODOLOGY/PRINCIPAL FINDINGS: μCT and ¹⁸F-FDG μPET were used to detect and quantify tumor lesions after treatment with the genotoxic carcinogen NDEA, the tumor promoting agent BHT or the hepatotoxin paracetamol. Tumor growth was investigated between the ages of 4 to 8.5 months and contrast-enhanced μCT imaging detected liver lesions as well as metastatic spread with high sensitivity and accuracy as confirmed by histopathology. Significant differences in the onset of tumor growth, tumor load and glucose metabolism were observed when the NDEA treatment group was compared with any of the other treatment groups. NDEA treatment of c-Myc transgenic mice significantly accelerated tumor growth and caused metastatic spread of HCC in to lung but this treatment also induced primary lung cancer growth. In contrast, BHT and paracetamol did not promote hepatocarcinogenesis. CONCLUSIONS/SIGNIFICANCE: The present study evidences the accuracy of in vivo imaging in defining tumor growth, tumor load, lesion number and metastatic spread. Consequently, the application of in vivo imaging techniques to transgenic animal models may possibly enable short-term cancer bioassays to significantly improve hazard identification and follow-up examinations of different organs by non-invasive methods.

  18. c-Myc modulates glucose metabolism via regulation of miR-184/PKM2 pathway in clear-cell renal cell carcinoma.

    Science.gov (United States)

    Huang, Jiwei; Kong, Wen; Zhang, Jin; Chen, Yonghui; Xue, Wei; Liu, Dongming; Huang, Yiran

    2016-10-01

    Renal cell carcinoma (RCC) is one of the most malignant tumors worldwide. Among all subtypes of RCC, clear-cell RCC (ccRCC) is the most common and aggressive one. The difficulty in overcoming resistance of traditional treatment is a threat for ccRCC therapies. Therefore, to understand the mechanism that underlies ccRCC progression is critical for new drug development. In the present study, we identified that miR-184 could be downregulated by c-Myc, which is different from the standard opinion that c-Myc is a target of miR-184. Overexpression of pre-miR-184 changed the metabolic and proliferation features of ccRCC cells by reducing cell glucose consumption, lactate production and cell proliferation. Further analysis by computer bioinformatics revealed that PKM2 is a target of miR-184. Both PKM2 mRNA and protein were significantly affected by addition of miR-184. Importantly, the PKM2 expression level was indeed increased in ccRCC samples, which is totally reverse compared to the decreased miR-184 expression level. Interestingly, we found that when PKM2 was knocked down in ccRCC cells, the rapid proliferation, high glucose consumption and high lactate production were all clearly inhibited, which indicates metabolic reprogramming and cancer progression blocking the in ccRCC cells. Our findings shed new light on ccRCC molecular study and provide a new and solid basis for developing ccRCC therapy.

  19. c-Myc Alters Substrate Utilization and O-GlcNAc Protein Posttranslational Modifications without Altering Cardiac Function during Early Aortic Constriction.

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    Dolena Ledee

    Full Text Available Hypertrophic stimuli cause transcription of the proto-oncogene c-Myc (Myc. Prior work showed that myocardial knockout of c-Myc (Myc attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we assessed the interplay between Myc, substrate oxidation and cardiac function during early pressure overload hypertrophy. Mice with cardiac specific, inducible Myc knockout (MycKO-TAC and non-transgenic littermates (Cont-TAC were subjected to transverse aortic constriction (TAC; n = 7/group. Additional groups underwent sham surgery (Cont-Sham and MycKO-Sham, n = 5 per group. After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. In sham hearts, Myc knockout did not affect cardiac function or substrate preferences for the citric acid cycle. However, Myc knockout altered fractional contributions during TAC. The unlabeled fractional contribution increased in MycKO-TAC versus Cont-TAC, whereas ketone and free fatty acid fractional contributions decreased. Additionally, protein posttranslational modifications by O-GlcNAc were significantly greater in Cont-TAC versus both Cont-Sham and MycKO-TAC. In conclusion, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy, which may regulate Myc-induced metabolic changes.

  20. Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc

    International Nuclear Information System (INIS)

    Oridonin, a tetracycline diterpenoid compound, has the potential antitumor activities. Here, we evaluate the antitumor activity and action mechanisms of oridonin in colorectal cancer. Effects of oridonin on cell proliferation were determined by using a CCK-8 Kit. Cell cycle distribution was determined by flow cytometry. Apoptosis was examined by analyzing subdiploid population and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Senescent cells were determined by senescence-associated β-galactosidase activity analysis. Semi-quantitative RT-PCR was used to examine the changes of mRNA of p16, p21, p27 and c-myc. The concomitant changes of protein expression were analyzed with Western blot. Expression of AcH3 and AcH4 were examined by immunofluorescence staining and Western blots. Effects of oridonin on colony formation of SW1116 were examined by Soft Agar assay. The in vivo efficacy of oridonin was detected using a xenograft colorectal cancer model in nude mice. Oridonin induced potent growth inhibition, cell cycle arrest, apoptosis, senescence and colony-forming inhibition in three colorectal cancer cell lines in a dose-dependent manner in vitro. Daily i.p. injection of oridonin (6.25, 12.5 or 25 mg/kg) for 28 days significantly inhibited the growth of SW1116 s.c. xenografts in BABL/C nude mice. With western blot and reverse transcription-PCR, we further showed that the antitumor activities of oridonin correlated with induction of histone (H3 and H4) hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression. Oridonin possesses potent in vitro and in vivo anti-colorectal cancer activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, oridonin may represent a novel therapeutic option in colorectal cancer treatment

  1. Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc

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    Zhao Ying-Zheng

    2010-11-01

    Full Text Available Abstract Background Oridonin, a tetracycline diterpenoid compound, has the potential antitumor activities. Here, we evaluate the antitumor activity and action mechanisms of oridonin in colorectal cancer. Methods Effects of oridonin on cell proliferation were determined by using a CCK-8 Kit. Cell cycle distribution was determined by flow cytometry. Apoptosis was examined by analyzing subdiploid population and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Senescent cells were determined by senescence-associated β-galactosidase activity analysis. Semi-quantitative RT-PCR was used to examine the changes of mRNA of p16, p21, p27 and c-myc. The concomitant changes of protein expression were analyzed with Western blot. Expression of AcH3 and AcH4 were examined by immunofluorescence staining and Western blots. Effects of oridonin on colony formation of SW1116 were examined by Soft Agar assay. The in vivo efficacy of oridonin was detected using a xenograft colorectal cancer model in nude mice. Results Oridonin induced potent growth inhibition, cell cycle arrest, apoptosis, senescence and colony-forming inhibition in three colorectal cancer cell lines in a dose-dependent manner in vitro. Daily i.p. injection of oridonin (6.25, 12.5 or 25 mg/kg for 28 days significantly inhibited the growth of SW1116 s.c. xenografts in BABL/C nude mice. With western blot and reverse transcription-PCR, we further showed that the antitumor activities of oridonin correlated with induction of histone (H3 and H4 hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression. Conclusion Oridonin possesses potent in vitro and in vivo anti-colorectal cancer activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, oridonin may represent a novel therapeutic option in colorectal cancer treatment.

  2. Genetic dissimilarity between primary colorectal carcinomas and their lymph node metastases: ploidy, p53, bcl-2, and c-myc expression--a pilot study.

    Science.gov (United States)

    Zalata, Khaled Refaat; Elshal, Mohamed Farouk; Foda, Abd AlRahman Mohammad; Shoma, Ashraf

    2015-08-01

    The current paradigm of metastasis proposes that rare cells within primary tumors acquire metastatic capability via sequential mutations, suggesting that metastases are genetically dissimilar from their primary tumors. This study investigated the changes in the level of expression of a well-defined panel of cell proliferation, differentiation, and apoptosis markers between the primary colorectal cancer (CRC) and the corresponding synchronous lymph node (LN) metastasis from the same patients. DNA flow cytometry and immunostaining of p53, bcl-2, and c-myc were carried out on 36 cases of CRC radical resection specimens with their corresponding LN metastases. There was very low probability that the histological patterns of primary tumors and LN metastases are independent (p < 0.001). Metastatic tumors were significantly more diffusely positive for p53 than the primary tumors (p < 0.001). Conversely, primary tumors were significantly more diffusely positive for c-myc than metastatic tumors (p = 0.011). No significant difference was found between the LNs and the primary tumors in bcl-2 positivity (p = 0.538) and DNA aneuploidy (p = 0.35), with a tendency towards negative bcl-2 and less aneuploidy in LN metastases than primary tumors. In conclusion, LN metastatic colorectal carcinomas have a tendency of being less differentiated, with a higher incidence of diffuse p53 staining, lower incidence of bcl-2 staining, and less aneuploidy in comparison to their primary counterparts suggesting a more aggressive biological behavior, which could indicate the necessity for more aggressive adjuvant therapy. PMID:25840688

  3. Alterations in TP53, cyclin D2, c-Myc, p21WAF1/CIP1 and p27KIP1 expression associated with progression in B-CLL

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    Antosz Halina

    2010-04-01

    Full Text Available B-cell chronic lymphocytic leukaemia (B-CLL originates from B lymphocytes that may differ in the activationlevel, maturation state or cellular subgroups in peripheral blood. Tumour progression in CLL B cells seems to result in gradualaccumulation of the clone of resting B lymphocytes in the early phases (G0/G1 of the cell cycle. The G1 phase isimpaired in B-CLL. We investigated the gene expression of five key cell cycle regulators: TP 53, c-Myc, cyclin D2,p21WAF1/CIP1 and p27KIP1, which primarily regulate the G1 phase of the cell cycle, or S-phase entry and ultimately controlthe proliferation and cell growth as well as their role in B-CLL progression. The study was conducted in peripheral bloodCLL lymphocytes of 40 previously untreated patients. Statistical analysis of correlations of TP53, cyclin D2, c-Myc,p21WAF1/CIP1 and p27KIP1 expressions in B-CLL patients with different Rai stages demonstrated that the progression of diseasewas accompanied by increases in p53, cyclin D2 and c-Myc mRNA expression. The expression of p27KIP1 was nearlystatistically significant whereas that of p21 WAF1/CIP1 showed no such correlation. Moreover, high expression levels of TP53and c-Myc genes were found to be closely associated with more aggressive forms of the disease requiring earlier therapy.

  4. Effect of Dihuang Guanshitong Granules on c-myc, TERT Protein Expression in Esophageal Cancer Rat Model after Radiotherapy%地黄管食通颗粒对放射治疗后食管癌模型大鼠c-myc,TERT表达的影响

    Institute of Scientific and Technical Information of China (English)

    王祥麒; 郑玉玲; 王俊涛; 韩倩倩

    2011-01-01

    观察地黄管食通颗粒对食管癌造模大鼠细胞凋亡及放疗后原癌基因( c-myc),端粒酶逆转录酶(TERT)蛋白表达的影响,从分子生物学角度分析其作用机制.方法 选用清洁级Wistar大鼠,除空白对照组(正常组)外,其余大鼠均以甲基戊基亚硝胺5 mg·kg -1sc,每周1次,连续18周,确定造模成功后,除模型组大鼠外,余造模大鼠均以戊巴比妥钠麻醉,钴60放射治疗机进行食管局部照射.末次照射24 h后,随机分为放疗组、地黄管食通高、中、低剂量组、六味地黄丸(阳性对照4.5g·kg-1)组,分别ig,连续35 d.应用TUNEL法检测对食管癌癌细胞凋亡的促进作用;免疫组化检测大鼠食管细胞中c-myc,TERT蛋白的表达.结果 ①TUNEL法检测各组均见有细胞凋亡,且药物治疗各组细胞凋亡指数明显增高,高剂量组细胞凋亡明显增多.②免疫组化结果显示c-myc蛋白在模型组、放疗组表达率及表达强度均明显增高,药物治疗组均有不同程度的降低,以高剂量组降低最明显(P<0.05),高剂量组与放疗组比较有统计学意义(P<0.05).③与放疗组比较,各药物组TERT蛋白表达均呈递减趋势,高、中、低剂量组有统计学意义(P<0.01,P<0.05).结论 诱导细胞凋亡是地黄管食通颗粒在体内杀伤食管癌细胞的作用机制之一,而这一作用机制与抑制c -myc,TERT蛋白的表达相关;该药物还可有效改善食管癌化疗后副作用,并预防复发.%Objective: To observe the effect of a combination of traditional Chinese herbs Dihuang Cuanshitong Granules on the rat model of esophageal cancer after rradiotherapy for inducing apoptosis and the c-myc, TERT protein expression. Method: Wistar rats were randomly divided into 2 groups. They were treated with MAN A 5 mg·kg-1 by subsutaneous injection except control group (the normal). After the model was successful, the model rats were treated with Intraperitoneal injection of sodium

  5. Genomic amplification patterns of human telomerase RNA gene and C-MYC in liquid-based cytological specimens used for the detection of high-grade cervical intraepithelial neoplasia

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    Chen Shaomin

    2012-04-01

    Full Text Available Abstract Background The amplification of oncogenes initiated by high-risk human papillomavirus (HPV infection is an early event in cervical carcinogenesis and can be used for cervical lesion diagnosis. We measured the genomic amplification rates and the patterns of human telomerase RNA gene (TERC and C-MYC in the liquid-based cytological specimens to evaluate the diagnostic characteristics for the detection of high-grade cervical lesions. Methods Two hundred and forty-three residual cytological specimens were obtained from outpatients aged 25 to 64 years at Qilu Hospital, Shandong University. The specimens were evaluated by fluorescence in situ hybridization (FISH using chromosome probes to TERC (3q26 and C-MYC (8q24. All of the patients underwent colposcopic examination and histological evaluation. A Chi-square test was used for categorical data analysis. Results In the normal, cervical intraepithelial neoplasia grade 1 (CIN1, grade 2 (CIN2, grade 3 (CIN3 and squamous cervical cancer (SCC cases, the TERC positive rates were 9.2%, 17.2%, 76.2%, 100.0% and 100.0%, respectively; the C-MYC positive rates were 20.7%, 31.0%, 71.4%, 81.8% and 100.0%, respectively. The TERC and C-MYC positive rates were higher in the CIN2+ (CIN2, CIN3 and SCC cases than in the normal and CIN1 cases (p p p > 0.05. Conclusions The TERC test is highly sensitive and is therefore suitable for cervical cancer screening. The C-MYC test is not suitable for cancer screening because of its lower sensitivity. The amplification patterns of TERC become more diverse and complex as the severity of cervical diseases increases, whereas for C-MYC, the amplification patterns are similar between the normal/CIN1 and CIN2+ groups. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1308004512669913.

  6. c-Myc plays a key role in TADs-induced apoptosis and cell cycle arrest in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Zhang, Dongdong; Qi, Junpeng; Liu, Rui; Dai, Bingling; Ma, Weina; Zhan, Yingzhuan; Zhang, Yanmin

    2015-01-01

    Cancer cell growth is complicated progression which is regulated and controlled by multiple factors including cell cycle, migration and apoptosis. In present study, we report that TADs, a novel derivative of taspine, has an essential role in resisting hepatocellular carcinoma growth (including arrest cell cycle) and migration, and inducing cell apoptosis. Our findings demonstrated that the TADs showed good inhibition on the hepatoma cell growth and migration, and good action on apoptosis induction. Using genome-wide microarray analysis, we found the down-regulated growth and apoptosis factors, and selected down-regulated genes were confirmed by Western blot. Knockdown of a checkpoint c-Myc by siRNA significantly attenuated tumor inhibition and apoptosis effects of TADs. Moreover, our results indicated TADs could simultaneously increase cyclin D1 protein levels and decrease amount of cyclin E, cyclin B1 and cdc2 of the cycle proteins, and also TADs reduced Bcl-2 expression, and upregulated Bad, Bak and Bax activities. In conclusion, these results illustrated that TADs is a key factor in growth and apoptosis signaling inhibitor, has potential in cancer therapy. PMID:26045987

  7. 4EBP1/c-MYC/PUMA and NF-κB/EGR1/BIM pathways underlie cytotoxicity of mTOR dual inhibitors in malignant lymphoid cells.

    Science.gov (United States)

    Yun, Seongseok; Vincelette, Nicole D; Knorr, Katherine L B; Almada, Luciana L; Schneider, Paula A; Peterson, Kevin L; Flatten, Karen S; Dai, Haiming; Pratz, Keith W; Hess, Allan D; Smith, B Douglas; Karp, Judith E; Hendrickson, Andrea E Wahner; Fernandez-Zapico, Martin E; Kaufmann, Scott H

    2016-06-01

    The mammalian target of rapamycin (mTOR), a kinase that regulates proliferation and apoptosis, has been extensively evaluated as a therapeutic target in multiple malignancies. Rapamycin analogs, which partially inhibit mTOR complex 1 (mTORC1), exhibit immunosuppressive and limited antitumor activity, but sometimes activate survival pathways through feedback mechanisms involving mTORC2. Thus, attention has turned to agents targeting both mTOR complexes by binding the mTOR active site. Here we show that disruption of either mTOR-containing complex is toxic to acute lymphocytic leukemia (ALL) cells and identify 2 previously unrecognized pathways leading to this cell death. Inhibition of mTORC1-mediated 4EBP1 phosphorylation leads to decreased expression of c-MYC and subsequent upregulation of the proapoptotic BCL2 family member PUMA, whereas inhibition of mTORC2 results in nuclear factor-κB-mediated expression of the Early Growth Response 1 (EGR1) gene, which encodes a transcription factor that binds and transactivates the proapoptotic BCL2L11 locus encoding BIM. Importantly, 1 or both pathways contribute to death of malignant lymphoid cells after treatment with dual mTORC1/mTORC2 inhibitors. Collectively, these observations not only provide new insight into the survival roles of mTOR in lymphoid malignancies, but also identify alterations that potentially modulate the action of mTOR dual inhibitors in ALL. PMID:26917778

  8. Generation of liver-specific TGF-α/c-Myc-overexpressing porcine induced pluripotent stem-like cells and blastocyst formation using nuclear transfer.

    Science.gov (United States)

    Park, Kyung-Mee; Lee, Joohyeong; Hussein, Kamal Hany; Hong, Seok-Ho; Yang, Se-Ran; Lee, Eunsong; Woo, Heung-Myong

    2016-05-01

    Transgenic porcine induced pluripotent stem (iPS) cells are attractive cell sources for the development of genetically engineered pig models, because they can be expanded without senescence and have the potential for multiple gene manipulation. They are also useful cell sources for disease modeling and treatment. However, the generation of transgenic porcine iPS cells is rare, and their embryonic development after nuclear transfer (NT) has not yet been reported. We report here the generation of liver-specific oncogenes (TGF-α/c-Myc)-overexpressing porcine iPS (T/M iPS)-like cells. They expressed stem cell characteristics and were differentiated into hepatocyte-like cells that express oncogenes. We also confirmed that NT embryos derived from T/M iPS-like cells successfully developed blastocysts in vitro. As an initial approach toward porcine transgenic iPS cell generation and their developmental competence after NT, this study provides foundations for the efficient generation of genetically modified porcine iPS cells and animal models. PMID:26725870

  9. Cloning and characterization of rabbit POU5F1, SOX2, KLF4, C-MYC and NANOG pluripotency-associated genes.

    Science.gov (United States)

    Táncos, Zsuzsanna; Bock, István; Nemes, Csilla; Kobolák, Julianna; Dinnyés, András

    2015-07-25

    While the rabbit (Oryctolagus cuniculus) is an important research model for aspects of human development and disease that cannot be studied in rodents, the lack of data on the genetic regulation of rabbit preimplantation development is a limitation. To assist in the understanding of this process, our aim was to isolate and characterize genes necessary for the induction and maintenance of cellular pluripotency. We are the first to report the isolation of complete coding regions of rabbit SOX2, KLF4, C-MYC and NANOG, which encode transcription factors that play crucial regulatory roles during early mammalian embryonic development. We determined the exon-intron boundaries and chromosomal localization of these genes using computational analysis. The sequences of mRNA and translated protein of the newly identified genes and those of POU5F1 were aligned to their mammalian orthologs to determine the degree of evolutionary conservation. Furthermore, the expression of these genes in embryonic and adult cells was studied at the mRNA and protein levels. We found the sequences and the expression pattern of these pluripotency-associated genes to be highly conserved between human and rabbit, indicating that the rabbit would be a valuable model for human preimplantation development. Implementing the newly identified genes either as biomarkers or as reprogramming factors might also pave the way towards the creation of stable pluripotent rabbit cell lines. PMID:25895477

  10. miR-34a induces cellular senescence via modulation of telomerase activity in human hepatocellular carcinoma by targeting FoxM1/c-Myc pathway.

    Science.gov (United States)

    Xu, Xinsen; Chen, Wei; Miao, Runchen; Zhou, Yanyan; Wang, Zhixin; Zhang, Lingqiang; Wan, Yong; Dong, Yafeng; Qu, Kai; Liu, Chang

    2015-02-28

    Increasing evidence suggests that miRNAs can act as either tumor suppressors or oncogenes in carcinogenesis. In the present study, we identified the role of miR-34a in regulating telomerase activity, with subsequent effect on cellular senescence and viability. We found the higher expression of miR-34a was significantly correlated with the advanced clinicopathologic parameters in hepatocellular carcinoma. Furthermore, tumor tissues of 75 HCC patients demonstrated an inverse correlation between the miR-34a level and telomere indices (telomere length and telomerase activity). Transient introduction of miR-34a into HCC cell lines inhibited the telomerase activity and telomere length, which induced senescence-like phenotypes and affected cellular viability. We discovered that miR-34a potently targeted c-Myc and FoxM1, both of which were involved in the activation of telomerase reverse transcriptase (hTERT) transcription, essential for the sustaining activity of telomerase to avoid senescence. Taken together, our results demonstrate that miR-34a functions as a potent tumor suppressor through the modulation of telomere pathway in cellular senescence. PMID:25686834

  11. 原癌基因c-myc真核表达载体构建及其生物学作用%Construction and identification of an original oncogene c-myc eukaryotic expression vector

    Institute of Scientific and Technical Information of China (English)

    荆志波; 韦丹丹; 逄越

    2013-01-01

    目的 利用基因工程技术构建携带原癌基因c-myc的真核表达载体pIRES2-AcGFPl-Nuc-c-myc重组质粒并在Hela细胞中表达.方法 以构建好的表达质粒pET28a-c-myc为基础,利用PCR方法扩增c-myc基因,并加入EcoR Ⅰ和SmaⅠ酶切位点,克隆至pMD 19-T Simple载体,双酶切后将其与同样经过双酶切的真核表达载体pIRES2-AcGFP1-Nuc连接,通过PCR、酶切及测序鉴定重组质粒的正确性,再将重组质粒pIRES2-AcGFPl-Nuc-c-myc转染Hela细胞,利用荧光显微镜观察GFP表达,利用MTT和免疫印迹证实c-myc蛋白表达量提高.结果 经PCR和酶切鉴定与预期结果相符,测序结果与GenBank中报道的序列完全一致,成功构建了重组表达质粒.免疫印迹证实c-myc基因在Hela细胞中得到表达.MTT结果显示Hela细胞数量显著增加.结论 真核表达载体pIRES2-AcGFP 1-Nuc-c-myc成功构建,c-myc基因在Hela细胞中成功表达,具有生物学活性.%This study designed to construct and express original oncogene c-myc eukaryotic expression vector pIRES2-AcGFP1-Nuc-c-myc using gene engineering technique.The c-myc gene was obtained by PCR amplification from pET28a-c-myc,to constructed pIRES2-AcGFPl-Nuc eukaryotic expression vector,which was then confirmed by PCR method,restriction analysis and DNA sequencing.In addition,the recombinant plasmid pIRES2-AcGFPl-Nuc-c-myc was transfected to Hela cells,and green fluorescent protein was expressed successfully under fluorescence microscopy.Analysis of Western blotting showed that c-myc protein expression was increased in Hela cell,and MTT assay indicated c-myc protein could promote the proliferation of Hela cells.In conclusion,eukaryotic expression vector of c-myc gene was constructed and transfected,which lay foundation for the lamprey cell line research.

  12. Estrogen Receptor-α and Its Target Gene c-Myc and Pre-implantation Embryos%雌激素受体α及其靶基因c-Myc与植入前胚

    Institute of Scientific and Technical Information of China (English)

    张燕琴

    2012-01-01

    Estrogen receptor-α(Erα), member of the steroid hormone receptor gene superfamily that acts as ligand-inducible transcription factor and plays an important role in regulating the proliferation, differentiation and development of cells and tissues. C-Myc,the Erα target gene,which belongs to Myc gene family, is a kind of nucleoprotein class protooncogene. Erα regulates the expression of c-Myc, at the same time,the expression of c-Myc changing also affects the function of Erα,they are associated with each other. Erα and c-Myc expression are stage-specific in preimplantation embryos, suggesting that their functions might be involved in the development of mammalian preimplantation embryos.%雌激素受体α(ERα)属于类固醇激素受体超家族,是细胞核中需要配体激活的转录因子,对细胞和组织的增殖、分化和发育有重要的调节作用.c-Myc是ERα目的 基因,属于Myc基因家族,是一种核蛋白类的原癌基因.ERα调控着c-Myc的表达,而c-Myc的表达变化也影响着ERα的功能发挥,彼此之间存在关联.它们在哺乳动物植入前胚中呈阶段特异性表达,在植入前胚发育中发挥一定作用.

  13. Suppression of c-Myc is involved in multi-walled carbon nanotubes' down-regulation of ATP-binding cassette transporters in human colon adenocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhaojing [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China); Xu, Yonghong [Institute of Ophthalmological Research, Department of Ophthalmology, Renmin Hospital of Wuhan University, 430060 Wuhan (China); Meng, Xiangning [School of Materials and Metallurgy, Northeastern University, Shenyang 110819 (China); Watari, Fumio [Department of Biomedical, Dental Materials and Engineering, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586 (Japan); Liu, Hudan, E-mail: hudanliu@hust.edu.cn [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China); Chen, Xiao, E-mail: mornsmile@yahoo.com [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China)

    2015-01-01

    Over-expression of ATP-binding cassette (ABC) transporters, a large family of integral membrane proteins that decrease cellular drug uptake and accumulation by active extrusion, is one of the major causes of cancer multi-drug resistance (MDR) that frequently leads to failure of chemotherapy. Carbon nanotubes (CNTs)-based drug delivery devices hold great promise in enhancing the efficacy of cancer chemotherapy. However, CNTs' effects on the ABC transporters remain under-investigated. In this study, we found that multiwalled carbon nanotubes (MWCNTs) reduced transport activity and expression of ABC transporters including ABCB1/Pgp and ABCC4/MRP4 in human colon adenocarcinoma Caco-2 cells. Proto-oncogene c-Myc, which directly regulates ABC gene expression, was concurrently decreased in MWCNT-treated cells and forced over-expression of c-Myc reversed MWCNTs' inhibitory effects on ABCB1 and ABCC4 expression. MWCNT-cell membrane interaction and cell membrane oxidative damage were observed. However, antioxidants such as vitamin C, β-mecaptoethanol and dimethylthiourea failed to antagonize MWCNTs' down-regulation of ABC transporters. These data suggest that MWCNTs may act on c-Myc, but not through oxidative stress, to down-regulate ABC transporter expression. Our findings thus shed light on CNTs' novel cellular effects that may be utilized to develop CNTs-based drug delivery devices to overcome ABC transporter-mediated cancer chemoresistance.

  14. Suppression of c-Myc is involved in multi-walled carbon nanotubes' down-regulation of ATP-binding cassette transporters in human colon adenocarcinoma cells

    International Nuclear Information System (INIS)

    Over-expression of ATP-binding cassette (ABC) transporters, a large family of integral membrane proteins that decrease cellular drug uptake and accumulation by active extrusion, is one of the major causes of cancer multi-drug resistance (MDR) that frequently leads to failure of chemotherapy. Carbon nanotubes (CNTs)-based drug delivery devices hold great promise in enhancing the efficacy of cancer chemotherapy. However, CNTs' effects on the ABC transporters remain under-investigated. In this study, we found that multiwalled carbon nanotubes (MWCNTs) reduced transport activity and expression of ABC transporters including ABCB1/Pgp and ABCC4/MRP4 in human colon adenocarcinoma Caco-2 cells. Proto-oncogene c-Myc, which directly regulates ABC gene expression, was concurrently decreased in MWCNT-treated cells and forced over-expression of c-Myc reversed MWCNTs' inhibitory effects on ABCB1 and ABCC4 expression. MWCNT-cell membrane interaction and cell membrane oxidative damage were observed. However, antioxidants such as vitamin C, β-mecaptoethanol and dimethylthiourea failed to antagonize MWCNTs' down-regulation of ABC transporters. These data suggest that MWCNTs may act on c-Myc, but not through oxidative stress, to down-regulate ABC transporter expression. Our findings thus shed light on CNTs' novel cellular effects that may be utilized to develop CNTs-based drug delivery devices to overcome ABC transporter-mediated cancer chemoresistance

  15. Transcriptome Analysis of WHV/c-myc Transgenic Mice Implicates Cytochrome P450 Enzyme 17A1 as a Promising Biomarker for Hepatocellular Carcinoma.

    Science.gov (United States)

    Wang, Feng; Huang, Jian; Zhu, Zhu; Ma, Xiao; Cao, Li; Zhang, Yongzhi; Chen, Wei; Dong, Yang

    2016-09-01

    Early detection of hepatocellular carcinoma (HCC) is critical for successful treatment and favorable prognosis. To identify novel HCC biomarkers, we used the WHV/c-myc transgenic (Tg) mice, an animal model of hepatocarcinogenesis. By analyzing their gene expression profiling, we investigated differentially expressed genes in livers of wild-type and Tg mice. The cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1), a hepatic P450 enzyme, was revealed to be overexpressed in the liver tissues of Tg mice at both preneoplastic and neoplastic stages. Mouse-to-human validation demonstrated that CYP17A1 mRNA and protein were also significantly increased in human HCC tissues compared with paired nontumor tissues (P = 0.00041 and 0.00011, respectively). Immunohistochemical studies showed that CYP17A1 was overexpressed in 67% (58 of 87) of HCC, and strong staining of CYP17A1 was observed in well-differentiated HCCs. Consistent with this, the median serum levels of CYP17A1 were also significantly higher in patients with HCC (140.2 ng/mL, n = 776) compared with healthy controls (31.4 ng/mL, n = 366) and to those with hepatitis B virus (57.5 ng/mL, n = 160), cirrhosis (46.1 ng/mL, n = 147), lung cancer (27.4 ng/mL, n = 109), and prostate cancer (42.1 ng/mL, n = 130; all P AFP-negative HCC cases. Altogether, through mouse-to-human search and validation, we found that CYP17A1 is overexpressed in HCCs and it has great potentiality as a noninvasive marker for HCC detection. These results provide a rationale for the future development and clinical application of CYP17A1 measurement to diagnose HCC more precisely. Cancer Prev Res; 9(9); 739-49. ©2016 AACR. PMID:27339169

  16. Altered expression of Bcl-2, c-Myc, H-Ras, K-Ras, and N-Ras does not influence the course of mycosis fungoides

    Science.gov (United States)

    Maj, Joanna; Jankowska-Konsur, Alina; Plomer-Niezgoda, Ewa; Sadakierska-Chudy, Anna

    2013-01-01

    Introduction Data about genetic alterations in mycosis fungoides (MF) are limited and their significance not fully elucidated. The aim of the study was to explore the expression of various oncogenes in MF and to assess their influence on the disease course. Material and methods Skin biopsies from 27 MF patients (14 with early MF and 13 with advanced disease) and 8 healthy volunteers were analyzed by real-time polymerase chain reaction (PCR) to detect Bcl-2, c-Myc, H-Ras, K-Ras and N-Ras expression. All PCR reactions were performed using an Applied Biosystems 7900HT Fast Real-Time PCR System and interpreted using Sequence Detection Systems software which utilizes the comparative delta Ct method. The level of mRNA was normalized to GAPDH expression. All data were analyzed statistically. Results All evaluated oncogenes were found to be expressed in the skin from healthy controls and MF patients. Bcl-2 (–4.2 ±2.2 vs. –2.2 ±1.1; p = 0.01), H-Ras (–3.0 ±3.3 vs. 0.6 ±2.6; p = 0.01) and N-Ras (–3.6 ±2.0 vs. –1.1 ±2.4; p = 0.03) were expressed at significantly lower levels in MF. No relationships between oncogene expression and disease stage, presence of distant metastases and survival were observed (p > 0.05 for all comparisons). Conclusions The pathogenic role and prognostic significance of analyzed oncogenes in MF seem to be limited and further studies are needed to establish better prognostic factors for patients suffering from MF. PMID:24273576

  17. Expressions of Pokemon and c-myc in colorectal cancer and their clinical significance%Pokemon和c-myc在结直肠癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    郭柏华; 杨章林; 董国钢; 王笑凌; 班雨

    2015-01-01

    目的 检测Pokemon和c-myc在结直肠癌、结直肠腺瘤和正常结直肠黏膜组织中的表达情况,研究结直肠癌组织中Pokemon和c-myc的表达与临床病理因素的关系.方法 收集86例结直肠癌患者肿瘤组织标本,60例结直肠腺瘤组织标本和40例正常结直肠黏膜组织标本.采用免疫组织化学法检测组织中Pokemon和c-myc蛋白表达情况,反转录聚合酶链反应检测组织中Pokemon和c-myc基因表达水平,并分析其与结直肠癌临床病理因素的关系.结果 结直肠癌组织中Pokemon和c-myc蛋白阳性表达率均明显高于结直肠腺瘤组织和正常结直肠黏膜组织[69.8%(60/86)比13.3%(8/60)和5.0%(2/40)、73.3%(63/86)比15.0%(9/60)和2.5%(1/40)],结直肠癌组织中Pokemon和c-myc基因表达水平均明显高于结直肠腺瘤组织和正常结直肠黏膜组织(0.915±0.247比0.358±0.102和0.277±0.085、1.272±0.360比0.398±0.153和0.255 ± 0.097),差异有统计学意义(P<0.05).结直肠癌组织中Pokemon和c-myc基因的表达水平与肿瘤浸润程度、肿瘤分化程度、淋巴结转移、远处转移和Dukes分期有关,差异有统计学意义(P<0.05),但与性别、年龄和肿瘤直径无关(P>0.05).结论 Pokemon和c-myc在结直肠癌组织中高表达,且这种表达与结直肠癌临床病理特征有关,提示Pokemon和c-myc可作为结直肠癌患者临床治疗的评估指标.%Objective To investigate the expressions of Pokemon and c-myc in colorectal cancer,colorectal adenomas and normal colorectal mucosa tissues,and demonstrate its relationship with clinicopathological features and prognosis in patients with colorectal cancer.Methods The specimens were taken from colorectal cancer tissue of 86 patients,colorectal adenomas tissue of 60 patients,and 40 normal colorectal mucosa tissue.The expressions of Pokemon and c-myc protein were detected by immunohistochemistry,and the expressions of Pokemon and c-myc gene were detected by reverse

  18. Pokemon mRNA在乳腺癌中的表达及与c- myc相关性分析%Expression of Pokemon mRNA in breast carcinoma and its relationship to c-myc

    Institute of Scientific and Technical Information of China (English)

    付朝江; 崔明; 徐衍; 王应霞

    2011-01-01

    目的:探讨人乳腺癌中原癌基因c-myc和Pokemon mRNA在乳腺癌组织中的表达及其与乳腺癌发生、转移的相关性.方法:收集浸润性导管癌组织、癌旁乳腺组织、正常乳腺组织各45、20和20例,用原位杂交法检测Pokemon mRNA表达,并用免疫组织化学法检测浸润性导管癌c-myc表达,并进行统计分析.结果:乳腺癌细胞质Pokemon mRNA的表达率为71.2%(37/45),显著高于癌旁正常乳腺组织40%(8/20)、乳腺增生组织25%(5/20), 三者有显著性差异 (P<0.05),细胞质c-myc阳性率分别为86.67%、60.0%、50.0%,三者有显著性差异(P<0.05).细胞质Pokemon mRNA表达与乳腺癌淋巴结转移、组织学分级相关(P<0.05).细胞质c-myc表达与乳腺癌腋窝淋巴结转移相关(P<0.05).45例乳腺癌细胞质Pokemon mRNA与c-myc表达呈正相关(γ=0.585 ,P<0.05).结论:Pokemon mRNA的表达可能在乳腺导管癌的组织发生中起关键作用,c-myc的过度表达可能与乳腺癌Pokemon基因转录激活有关.%Objective: To explore the expression and interaction of Pokemon mRNA and proto - oncogene c - myc in the course of carcinogenesis and metastasis of breast cancer.Methods : The expression of Pokemon mRNA was examined by in situhybridization in 45 cases of breast cancer,20 cases of adjacent noncancerous breast tissue and 20 cases of mammary gland hyperplasia,The expression of c - myc was examined by immunohistochemistry in 45 cases of carcinoma.Results:The rate of strong positive plasma Pokemon mRNA and c - myc expression was significandy higher in breast cancer than in adjacent noncancerous breast tissue and mammary gland hyperplasia ( P < 0.05 ) , the rates of strong positive plasma Pokemon expression were 71.2% ( 37/45 ) ,40% ( 8/20) , 25 % ( 5/20) ;86.67% 、60.0% 、50.0% , respectively.The positive expreasion of Pokemon mRNA and c - myc in breast cancer was strongly related to lympb nodemetastasis(P <0.05) .The expre8aion of Pokemon m

  19. 人胎冠状动脉原位杂交c-myc和jun原癌基因表达%Expression of proto - oncogenes c - myc and jun in human coronary artery ruring development

    Institute of Scientific and Technical Information of China (English)

    蔡维君; 陈新平; 伍校琼; 罗学港

    2004-01-01

    目的研究原癌基因c-myc和jun在人胎冠状动脉发育过程中的表达与平滑肌细胞增殖的关系.方法用原位杂交方法检测,胎龄分别为16周、22周(因治疗需要引产)的胎儿和意外死亡的足月胎儿冠状动脉前降支c-myc mRNA和jun mRNA的表达水平.杂交反应产物用图像分析仪(MIAS300)作定量分析.结果C-myc mRNA原位杂交反应产物与被测血管区域面积的百分比在16周、22周和足月胎儿分别是70、56和10;Jun mRNA的杂交信反应产物与被测血管区域面积的百分比在这三个时期分别是68、53和8.两个原癌基因在不同阶段的表达均具有显著性差异.结论本实验首次报道c-myc和jun在人胎冠状动脉发育过程中平滑肌的表达图型,c-myc和jun在胎儿冠状动脉平滑肌细胞增殖和内膜的形成过程中可能具有重要的调控作用.%Objective: To investigate the expression of protooncogenes, c - myc and jun, in human coronary artery during development. Methods: In situ hybridization was employed to detect c - myc mRNA and jun mRNA in human coronary artery from aborted fetus with embryonic ages from week 16 to 22 due to treatment requirements. In addition, 3 cases of full term human fetus died of accident were also studied. Hybridized signals were quantified with a computer - assisted image - analyzing system ( MIAS 300 ). Results: The ratio of hybridized signal of c - myc to the area of vascular wall detected were 0.7, 0.54 and 0.10 respectively corresponding to the embryonic ages, 16 weeks,22 weeks and full term. Similar results with the ratio of 0.68, 0.53 and 0.08 for jun mRNA at above embryonic ages was also found. The levels of c - myc and jun mRNA expressed at different embryonic stage showed a significant difference. Conclusions: We first reported the expression of proto - oncogenes, c - myc and jun, in human coronary artery during embryonic development. These two proto - oncogenes may play an important role in the

  20. 人类p53和c-myc同源基因在玉米颖果发育过程中的表达%Expressions of Human p53 and c-myc Gene Homologues During Caryopsis Development in Maize

    Institute of Scientific and Technical Information of China (English)

    亓翠英; 宁顺斌; 王宁; 李立家; 宋运淳

    2003-01-01

    肿瘤抑制基因p53和原癌基因c-myc已被证明在动物中高度保守并参与许多PCD过程.这两个基因编码的同源蛋白及其RNA在玉米中的存在已有报道,并且其DNA同源序列已利用荧光原位杂交定位在玉米相应的染色体上.利用免疫组织化学方法探测了与人类p53和c-myc基因同源的玉米基因在玉米颖果发育过程中的时空表达模式.结果发现,在授粉后的一定阶段,在反足细胞、珠被、未成熟的胚乳、子房壁、导管组织和糊粉层中,p53同源基因表达强烈,c-myc同源基因的表达相反,在授粉后的这些组织中基本不表达,而在授粉前的中央细胞的极核中表达水平较高.TUNEL检测显示,在p53同源基因呈现高水平表达的地方,DNA断裂信号强烈.在动物细胞中,p53和c-myc起相反的调节作用,这与其同源基因在玉米中的作用模式相似.由此说明p53和c-myc同源基因可能在玉米颖果发育PCD过程中起重要作用,并进一步推论高等植物PCD和动物细胞凋亡存在一定的保守性机制.%Tumor suppressor gene p53 and proto-oncogene c-myc have been proved to be highly conserved and participate in many PCD processes in animals.In maize,proteins and RNAs related to p53 and c-myc have already been reported and the sequences homologous to these two genes have also been localized onto maize chromosomes by FISH.In this study,using immunohistochemistry we investigated the expression patterns of maize genes homologous to human p53 and c-myc during caryopsis development stages in maize.In a giving stage after pollination,p53 homologue showed high levels in the antipodal cells,integument,immature endosperm,ovary wall,tracheary elements,and aleurone layer,while c-myc homologue showed low levels in these tissues,only before pollination showed high expression in polar nucleus.The results of TUNEL assay demonstrated that TUNEL positive signals were detected where p53 homologue showed high expression

  1. S-Adenosylmethionine Inhibits the Growth of Cancer Cells by Reversing the Hypomethylation Status of c-myc and H-ras in Human Gastric Cancer and Colon Cancer

    OpenAIRE

    Luo, Jin; Li, Yan-Ni; Wang, Fei; Zhang, Wei-ming; Geng, Xin

    2010-01-01

    A global DNA hypomethylation might activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-Adenosylmethionine (SAM) serves as a major methyl donor in biological transmethylation events. The object of this study is to explore the influence of SAM on the status of methylation at the promoter of the oncogenes c-myc, H-ras and tumor-suppressor gene p16 (INK4a), as well as its inhibitory effect on cancer cells. The results indicated that SAM treatment inhibited cell...

  2. In vitro effects of zinc and folic acid on the expressions of Neurogenin 3, Kruppel-like factor 4, c-Myc, Nanog, Nestin and POU class 5 homeobox 1 genes

    OpenAIRE

    Zehra Dilsad Coban; Sefik Guran; Atmaca Sahin Sagaltici

    2015-01-01

    Objective: Genes are regulated at multiple levels by using nutritional factors during neurogenesis and gliogenesis in brain development. Folic acid (FA)and zinc regulate the expressions of some genes which participate in brain development as nutritional factors. So, we aimed to find the effect of FA and zinc on the expression levels of neurogenin 3 (NGN3), Kruppel-like factor 4 (Klf4), c-Myc, nanog, POU class 5 homeobox 1-Pou5F1 (Oct4), and Nestin in mouse fetal brain tissue in neural plate p...

  3. Reevesioside A, a cardenolide glycoside, induces anticancer activity against human hormone-refractory prostate cancers through suppression of c-myc expression and induction of G1 arrest of the cell cycle.

    Directory of Open Access Journals (Sweden)

    Wohn-Jenn Leu

    Full Text Available In the past decade, there has been a profound increase in the number of studies revealing that cardenolide glycosides display inhibitory activity on the growth of human cancer cells. The use of potential cardenolide glycosides may be a worthwhile approach in anticancer research. Reevesioside A, a cardenolide glycoside isolated from the root of Reevesia formosana, displayed potent anti-proliferative activity against human hormone-refractory prostate cancers. A good correlation (r² = 0.98 between the expression of Na⁺/K⁺-ATPase α₃ subunit and anti-proliferative activity suggested the critical role of the α₃ subunit. Reevesioside A induced G1 arrest of the cell cycle and subsequent apoptosis in a thymidine block-mediated synchronization model. The data were supported by the down-regulation of several related cell cycle regulators, including cyclin D1, cyclin E and CDC25A. Reevesioside A also caused a profound decrease of RB phosphorylation, leading to an increased association between RB and E2F1 and the subsequent suppression of E2F1 activity. The protein and mRNA levels of c-myc, which can activate expression of many downstream cell cycle regulators, were dramatically inhibited by reevesioside A. Transient transfection of c-myc inhibited the down-regulation of both cyclin D1 and cyclin E protein expression to reevesioside A action, suggesting that c-myc functioned as an upstream regulator. Flow cytometric analysis of JC-1 staining demonstrated that reevesioside A also induced the significant loss of mitochondrial membrane potential. In summary, the data suggest that reevesioside A inhibits c-myc expression and down-regulates the expression of CDC25A, cyclin D1 and cyclin E, leading to a profound decrease of RB phosphorylation. G1 arrest is, therefore, induced through E2F1 suppression. Consequently, reevesioside A causes mitochondrial damage and an ultimate apoptosis in human hormone-refractory prostate cancer cells.

  4. A mouse strain defective in both T cells and NK cells has enhanced sensitivity to tumor induction by plasmid DNA expressing both activated H-Ras and c-Myc.

    Directory of Open Access Journals (Sweden)

    Li Sheng-Fowler

    Full Text Available As part of safety studies to evaluate the risk of residual cellular DNA in vaccines manufactured in tumorigenic cells, we have been developing in vivo assays to detect and quantify the oncogenic activity of DNA. We generated a plasmid expressing both an activated human H-ras gene and murine c-myc gene and showed that 1 µg of this plasmid, pMSV-T24-H-ras/MSV-c-myc, was capable of inducing tumors in newborn NIH Swiss mice. However, to be able to detect the oncogenicity of dominant activated oncogenes in cellular DNA, a more sensitive system was needed. In this paper, we demonstrate that the newborn CD3 epsilon transgenic mouse, which is defective in both T-cell and NK-cell functions, can detect the oncogenic activity of 25 ng of the circular form of pMSV-T24-H-ras/MSV-c-myc. When this plasmid was inoculated as linear DNA, amounts of DNA as low as 800 pg were capable of inducing tumors. Animals were found that had multiple tumors, and these tumors were independent and likely clonal. These results demonstrate that the newborn CD3 epsilon mouse is highly sensitive for the detection of oncogenic activity of DNA. To determine whether it can detect the oncogenic activity of cellular DNA derived from four human tumor-cell lines (HeLa, A549, HT-1080, and CEM, DNA (100 µg was inoculated into newborn CD3 epsilon mice both in the presence of 1 µg of linear pMSV-T24-H-ras/MSV-c-myc as positive control and in its absence. While tumors were induced in 100% of mice with the positive-control plasmid, no tumors were induced in mice receiving any of the tumor DNAs alone. These results demonstrate that detection of oncogenes in cellular DNA derived from four human tumor-derived cell lines in this mouse system was not possible; the results also show the importance of including a positive-control plasmid to detect inhibitory effects of the cellular DNA.

  5. Two-step stimulation of B lymphocytes to enter DNA synthesis: synergy between anti-immunoglobulin antibody and cytochalasin on expression of c-myc and a G1-specific gene.

    OpenAIRE

    Buckler, A J; Rothstein, T. L.; Sonenshein, G E

    1988-01-01

    Previously we demonstrated that stimulation of resting murine splenic B lymphocytes with goat anti-mouse immunoglobulin antibody (GaMIg) plus cytochalasin D (CD) led to DNA synthesis; GaMIg and CD added simultaneously, or GaMIg added before CD, induced this response (T. L. Rothstein, J. Immunol. 136:813-816, 1986). Cells similarly treated with GaMIg or CD alone did not enter S phase. Here we have measured the effects of this two-signal stimulation on the c-myc, 2F1, and gamma-actin genes. The...

  6. Correlation of expression VEGF to expression of protooncogenes of c-fos and c-myc at protein level among various grades of liver cirrhosis%硬变肝组织VEGF的表达与原癌基因c-fos,c-myc 以及肝功能分级的相关性研究

    Institute of Scientific and Technical Information of China (English)

    施宝民; 杨镇; 张黎; 李大鹏

    2001-01-01

    目的探讨血管内皮生长因子(VEGF)在肝硬化发生发展中的作用以及肝脏原癌基因(c-fos,c-myc)与肝功能Child分级的相关关系。方法通过对54例硬变肝组织中的VEGF、c-fos、c-myc蛋白的免疫组化检测,观察VEGF的蛋白水平表达与肝脏功能Child 分级的相关性,同时分析VEGF阳性病例组与阴性病例组c-fos、c-myc的不同表达,来了解二者的相互作用关系。结果 Child A级与Child B级VEGF的表达显著高于Child C级和对照组(P<0.05),而Child A级与Child B级之间差异无显著性意义(P>0.05)。c-fos 及c-myc的表达在VEGF阳性组和阴性组差异无显著性意义(P>0.05)。结论 VEGF的水平可以反映肝脏功能的代偿状态,可能在肝硬化的进程中起着保肝作用;原癌基因c-fos、c-myc与VEGF作用在不同环节。

  7. S-Adenosylmethionine Inhibits the Growth of Cancer Cells by Reversing the Hypomethylation Status of c-myc and H-ras in Human Gastric Cancer and Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jin Luo, Yan-Ni Li, Fei Wang, Wei-Ming Zhang, Xin Geng

    2010-01-01

    Full Text Available A global DNA hypomethylation might activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-Adenosylmethionine (SAM serves as a major methyl donor in biological transmethylation events. The object of this study is to explore the influence of SAM on the status of methylation at the promoter of the oncogenes c-myc, H-ras and tumor-suppressor gene p16 (INK4a, as well as its inhibitory effect on cancer cells. The results indicated that SAM treatment inhibited cell growth in gastric cancer cells and colon cancer cells, and the inhibition efficiency was significantly higher than that in the normal cells. Under standard growth conditions, C-myc and H-ras promoters were hypomethylated in gastric cancer cells and colon cancer cells. SAM treatment resulted in a heavy methylation of these promoters, which consequently downregulated mRNA and protein levels. In contrast, there was no significant difference in mRNA and protein levels of p16 (INK4a with and without SAM treatment. SAM can effectively inhibit the tumor cells growth by reversing the DNA hypomethylation on promoters of oncogenes, thus down-regulating their expression. With no influence on the expression of the tumor suppressor genes, such as P16, SAM could be used as a potential drug for cancer therapy.

  8. TA1 oncofetal rat liver cDNA and putative amino acid permease: temporal correlation with c-myc during acute CCl4 liver injury and variation of RNA levels in response to amino acids in hepatocyte cultures.

    Science.gov (United States)

    Shultz, V D; Campbell, W; Karr, S; Hixson, D C; Thompson, N L

    1999-01-01

    TA1 is a rat liver oncofetal cDNA and a member of an emerging family of evolutionarily conserved molecules with homology to amino acid transporters and permeases. The aim of these studies was to characterize the regulation and role of TA1 in acute rat liver injury by examining its relation to regeneration and metabolic stress. Following a single dose of CCl4, TA1 message was expressed 3-48 h. The major 3.3-kb TA1 transcript correlated temporally with c-myc expression. A novel 2.9-kb TA1 transcript was expressed more variably 24-48 h. TA1 protein was restricted to hepatocytes in G0 and G1 phases of the cell cycle. Relative to CCl4, a much smaller increase in TA1 was noted after partial hepatectomy and TA1 preceded the peak of c-myc expression. In vitro TA1 was not induced in hepatocytes by EGF or the acute-phase cytokines IL-6 and TNF-alpha, but was found to be modulated in response to amino acid availability. TA1 expression increased in media without arginine and glutamine and was repressed by total amino acid levels 5-fold over basal MEM. Together, these results contrast with the constitutive expression observed in transformed cells and suggest an adaptive role for TA1 during liver injury.

  9. Bromodichloromethane induces cell proliferation in different tissues of male F344 rats by suppression of E-cadherin expression via hypermethylation or transcriptional activation of c-myc and cyclin D1.

    Science.gov (United States)

    Liao, Jing; Li, Xiao-Feng; Zhou, Shun-Chang; Luo, Yan; Liu, Ai-Lin; Lu, Wen-Qing

    2013-11-25

    The aim of this study was to investigate the mechanism of bromodichloromethane (BDCM) - induced cell proliferation in different tissues of male F344 rats. Rats were administered at doses of 0 and 100mg/kg/day BDCM dissolved in corn oil by gavage for 5 days/week for 1, 4, 8 and 12 weeks. Then the colon, kidney and liver were collected. No histologic lesions were observed in the colon of rats exposed to BDCM, while there were mild nephrotoxicity and marginal hepatotoxicity related to BDCM treatment. Moreover, BDCM enhanced cell proliferation in the colon and kidney but not in the liver. In colons, hypermethylation in E-cadherin promoter might be associated with inhibition of mRNA and protein expression after 12 weeks of BDCM exposure. In kidneys, BDCM decreased E-cadherin mRNA expression, accompanying with transcriptional activation of c-myc and cyclin D1. However, suppression of E-cadherin mRNA and protein expression occurred in the absence of significant changes in DNA methylation. Therefore, suppression of E-cadherin expression via hypermethylation or transcriptional activation of c-myc and cyclin D1 may be involved in BDCM-induced cell proliferation in different tissues of male F344 rats.

  10. Differential regulation of LncRNA-SARCC suppresses VHL-mutant RCC cell proliferation yet promotes VHL-normal RCC cell proliferation via modulating androgen receptor/HIF-2α/C-MYC axis under hypoxia.

    Science.gov (United States)

    Zhai, W; Sun, Y; Jiang, M; Wang, M; Gasiewicz, T A; Zheng, J; Chang, C

    2016-09-15

    It is well established that hypoxia contributes to tumor progression in a hypoxia inducible factor-2α (HIF-2α)-dependent manner in renal cell carcinoma (RCC), yet the role of long noncoding RNAs (LncRNAs) involved in hypoxia-mediated RCC progression remains unclear. Here we demonstrate that LncRNA-SARCC (Suppressing Androgen Receptor in Renal Cell Carcinoma) is differentially regulated by hypoxia in a von Hippel-Lindau (VHL)-dependent manner both in RCC cell culture and clinical specimens. LncRNA-SARCC can suppress hypoxic cell cycle progression in the VHL-mutant RCC cells while derepress it in the VHL-restored RCC cells. Mechanism dissection reveals that LncRNA-SARCC can post-transcriptionally regulate androgen receptor (AR) by physically binding and destablizing AR protein to suppress AR/HIF-2α/C-MYC signals. In return, HIF-2α can transcriptionally regulate the LncRNA-SARCC expression via binding to hypoxia-responsive elements on the promoter of LncRNA-SARCC. The negative feedback modulation between LncRNA-SARCC/AR complex and HIF-2α signaling may then lead to differentially modulated RCC progression in a VHL-dependent manner. Together, these results may provide us a new therapeutic approach via targeting this newly identified signal from LncRNA-SARCC to AR-mediated HIF-2α/C-MYC signals against RCC progression.

  11. CDC4及c-Myc在胃癌中的表达及临床意义%The expressions of CDC4 and c-Myc in gastric cancer and their clinical signifieance

    Institute of Scientific and Technical Information of China (English)

    黄国全; 黎晖; 张才全; 吴泉峰; 孙建华

    2015-01-01

    targeted therapy for gastric cancer has become a research hotspot. The oncogene overexpression and the anti-oncogene lower expression are closely related with gastric cancer.CDC4/FBXW7 is an anti-oncogene, butc-Myc is an oncogene. The previous research showed that CDC4 affected the expression of many oncogenes, such as Cyclin E. This study aimed to investigate the expression of CDC4 and c-Myc in gastric cancer and to elucidate the potential relationship between their expressions and clinical pathological characteristics.Methods:Semi-quantitative reverse transcription polymerase chain reaction (sRT-PCR), immunohistochemistry and Western blot method were used to determine the mRNA and protein expressions of CDC4 and c-Myc in 40 specimens of gastric carcinoma tissues, corresponding adjacent tissues and normal mucosal tissues. The expressions of CDC4 and c-Myc and the clinical pathological characteristics were analyzed.Results:The protein expressions of CDC4 in gastric cancer tissues were signiifcantly lower than those in adjacent tissues and normal mucosal tissues (P<0.05), whereas the protein expression of c-Myc in gastric cancer tissues was signiifcantly higher than that in adjacent tissues and normal mucosal tissues (P<0.05). The protein and mRNA expression of CDC4 and c-Myc were correlated with differentiation, TNM stage, lymph node metastasis, inifltration, but not with patients’ gender, age and site of cancer (P<0.05). There was a signiifcant negative correlation between CDC4 and c-Myc at the mRNA and protein expression levels (P<0.05).Conclusion:The lower expression of CDC4 is correlated with differentiation, TNM stage, lymph node metastasis and inifltration. c-Myc overexpression is likely to be the CDC4 loss. It suggests that the loss of CDC4 may be a valuable marker for assessing the diagnosis and treatment and the prognosis of gastric cancer.

  12. Neuroprotective effects of prostaglandin A1 and its effect on IKK/IkB/NF-kB/c-myc signaling pathway in rat models of permanent focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Hui-lingZHANG; Zhen-lunGU; Zheng-hongQIN

    2005-01-01

    AIM Prostaglandin A1(PGA1) is a cyclopentenone prostaglandin. Recently, we reported that PGA1 can inhibit excitotoxin-induced apoptosis of striatal neurons in vivo and rotenone-induced apoptosis ofcultured SH-SY5Y cells, suggesting that PGA1 may have neuroprotective efficacy, possibly mediated by inhibition of NF-kB activation. The present study evaluated the neuroprotective potential of PGA1 and its effect on IKK/I( B/NF-kB/c-myc signaling pathway in rat models of permanent focal cerebral ischemia. METHODS Permanent middle cerebral artery occlusion (pMCAO) model was constructed by intraluminal suture cannulation through the internal carotid artery in Wistar rats.

  13. The Phosphoinositide 3-Kinase p110α Isoform Regulates Leukemia Inhibitory Factor Receptor Expression via c-Myc and miR-125b to Promote Cell Proliferation in Medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Fabiana Salm

    Full Text Available Medulloblastoma (MB is the most common malignant brain tumor in childhood and represents the main cause of cancer-related death in this age group. The phosphoinositide 3-kinase (PI3K pathway has been shown to play an important role in the regulation of medulloblastoma cell survival and proliferation, but the molecular mechanisms and downstream effectors underlying PI3K signaling still remain elusive. The impact of RNA interference (RNAi-mediated silencing of PI3K isoforms p110α and p110δ on global gene expression was investigated by DNA microarray analysis in medulloblastoma cell lines. A subset of genes with selectively altered expression upon p110α silencing in comparison to silencing of the closely related p110δ isoform was revealed. Among these genes, the leukemia inhibitory factor receptor α (LIFR α was validated as a novel p110α target in medulloblastoma. A network involving c-Myc and miR-125b was shown to be involved in the control of LIFRα expression downstream of p110α. Targeting the LIFRα by RNAi, or by using neutralizing reagents impaired medulloblastoma cell proliferation in vitro and induced a tumor volume reduction in vivo. An analysis of primary tumors revealed that LIFRα and p110α expression were elevated in the sonic hedgehog (SHH subgroup of medulloblastoma, indicating its clinical relevance. Together, these data reveal a novel molecular signaling network, in which PI3K isoform p110α controls the expression of LIFRα via c-Myc and miR-125b to promote MB cell proliferation.

  14. CyclinA、C-myc在皮肤瘢痕及瘢痕癌组织中的表达及意义%Expressions and Significance of CyclinA and C-myc in Skin Scar and Skin Scar Carcinoma

    Institute of Scientific and Technical Information of China (English)

    郭瑞珍; 周开梅; 王燕

    2011-01-01

    目的 探讨CyclinA、C-myc在皮肤病理性瘢痕和瘢痕癌组织中的表达及意义.方法以病理性皮肤瘢痕、皮肤瘢痕癌组织为研究对象,以正常皮肤组织为对照.采用免疫组织化学(SP法)分别检测CyclinA、C-myc蛋白的表达,采用核酸分子原位杂交法检测CyclinA mRNA的表达,所有数据输入计算机后运用SPSS 16.0软件包进行统计学分析.结果 (1)CyclinA、CyclinA mRNA在正常皮肤和皮肤瘢痕上皮中的表达呈阴性或弱阳性,在瘢痕癌组织中呈强阳性.瘢痕癌组的表达(平均吸光度和阳性面积)与正常皮肤组及皮肤瘢痕组比较,差异均有统计学意义(P<0.01);但正常皮肤组与瘢痕组比较,差异无统计学意义(P>0.05).(2)C-myc蛋白在正常皮肤中的表达呈弱阳性,在皮肤瘢痕上皮中呈阳性,在瘢痕癌组织中呈强阳性.且两两比较差异均有统计学意义(P<0.05).(3)相关分析显示,在皮肤瘢痕癌中,CyclinA与CyclinA mRNA(r=0.766,P<0.01)、CyclinA与C-myc蛋白(r=0.804,P<0.01)的表达均呈正相关.结论(1)CyclinA及其mRNA、C-myc的高表达,可能与皮肤瘢痕癌的发生有关;(2)C-myc蛋白的高表达与皮肤瘢痕上皮癌变有相关性.(3)在瘢痕癌中CyclinA同时存在蛋白水平和基因水平的异常表达.%Objective To study the expressions and significance of CyclinA and C-myc in skin Scar and skin Scar Carcinoma. Methods We compared pathological skin scar tissues and skin scar carcinoma tissues with normal skin tissues. The expression of CyclinA and C-myc proteins were detected by the immu-nohistochemical method of SP. And the expression of CyclinA mRNA was detected by in situ hybridization. All data were input into the computer and statistically analyzed with SPSS (16. 0) software. Results (1) CyclinA and its mRNA showed strong positive expression in scar carcinoma tissues, negative or weakly positive expression in normal skin epidermis and pathological skin scar epithelium

  15. 多态性上皮黏蛋白1和原癌基因C-myc在老年甲状腺乳头状癌患者中的表达%Expression changes of mucin1 and c-myc gene in elderly papillary thyroid carcinoma patient

    Institute of Scientific and Technical Information of China (English)

    胡耀杰; 罗晓燕; 杨岳; 陈春悠; 张志勇; 郭欣

    2014-01-01

    Objective To study the changes of expression of mucin1 (MUC1) and protooncogene proteins C-myc (C-myc) gene in elderly papillary thyroid carcinoma.Methods The expression levels of MUC1 and C-myc were examined by immunohistochemical methods in 58 sample of thyroid carcinoma,35 nodular goiter and in 30 normal thyroid tissue.Results The detective rate of MUC1 in 58 specimens of thyroid carcinoma was 77.6% (45/58),while 90.0% (9/10) in those with infiltration and 88.2 % (15/17) in those with metastasis.The detective rate of C-myc in 58 specimens of thyroid carcinoma was 81.0 % (47/58),and 100.0 % (17/17) in those with metastasis.Conclusions The differences in MUC1 or C myc expression and in thyroid carcinoma infiltration and lymph node metastasia between benign versus malignant thyroid tumor are statistically significant.%目的 探讨多态性上皮黏蛋白1 (mucin 1,MUC1)和原癌基因蛋白质(proto-oncogene proteins C-myc,C-Myc)基因在老年甲状腺乳头状癌(PTC)患者中的表达和临床意义. 方法 应用免疫组化法检测30例腺瘤旁正常甲状腺组织、35例结节性甲状腺肿和58例PTC标本中MUC1和C-myc的表达水平. 结果 MUC1基因在甲状腺癌中表达率为77.6%(45/58),MUC1在有局部浸润和淋巴结转移患者中的检出率分别为90.0%(9/10)和88.2%(15/17).C-myc基因在甲状腺癌中阳性率为81.0% (47/58);C-myc在淋巴结转移组中的检出率为100.0% (17/17). 结论 MUC1和C myc的阳性表达在甲状腺良恶性病变间有差异,并与甲状腺癌的转移有关.

  16. Effect of TGF-β1 on cell proliferation and c-myc expression in Burkitt lymphoma cell line%TGF-β1对Burkitt淋巴瘤细胞增殖及c-myc表达的影响

    Institute of Scientific and Technical Information of China (English)

    李柱虎; Lee Mija

    2006-01-01

    目的:探讨TGF-β1对Burkitt淋巴瘤细胞生长的抑制作用和对c-myc基因及蛋白表达的影响.方法:于Burkitt淋巴瘤细胞株Jiyoye中加入5ng/mL TGF-β1做为实验组,不加TGF-β1做为对照组,分别培养24、48和72 h,用MTT、RT-PCR及Westem blot方法检测细胞生存率、c-myc mRNA及蛋白的表达水平.结果:经TGF-β1处理24、48和72 h的Jiyoye细胞生存率分别为(80.5±3.14)%、(70.5±3.77)%和(56.4±3.36)%,与对照组相比均显著降低(t=8.788 0,P=0.012 7;t=13.570 9,P=0.005 4;t=22.500 6,P=0.019 7).经TGF-β1处理的Jiyoye细胞随时间的延长生存率降低,72 h时的生存率与24h相比差异有统计学意义,t=8.186 2,P=0.001 2;c-myc mRNA及蛋白的表达水平也明显变化,24 h开始下降,48和72 h时明显受抑制,与对照组相比差异有统计学意义,P=0.000 0.结论:TGF-β1可呈时间依赖性抑制Jiyoye细胞的生长,其机制可能与抑制c-myc基因及蛋白的表达有关.

  17. Antileukemia Effect of Ciclopirox Olamine Is Mediated by Downregulation of Intracellular Ferritin and Inhibition β-Catenin-c-Myc Signaling Pathway in Glucocorticoid Resistant T-ALL Cell Lines.

    Science.gov (United States)

    Wu, Jianrong; Liu, Huajun; Zhang, Ge; Gu, Ling; Zhang, Yanle; Gao, Ju; Wei, Yuquan; Ma, Zhigui

    2016-01-01

    Ciclopirox olamine (CPX) is an antifungal drug that has been reported to have antitumor effects. In this study we investigated the antileukemia effects and the possible mechanisms of CPX on glucocorticoid (GC)-resistant T-cell acute lymphoblastic leukemia (T-ALL) cell lines. The results indicated that CPX inhibited the growth of GC-resistant T-ALL cells in a time- and dose-dependent manner, and this effect was closely correlated with the downregulation of intracellular ferritin. CPX induced cell cycle arrest at G1 phase by upregulation of cyclin-dependent kinase (CDK) inhibitor of p21 and downregulation of the expressions of cyclin D, retinoblastoma protein (Rb), and phosphorylated Rb (pRb). CPX also enhanced apoptotic cell death by downregulation of anti-apoptotic proteins such as Bcl-2, Bcl-xL, and Mcl-1. More importantly, CPX demonstrated a strong synergistic antileukemia effect with GC and this effect was mediated, at least in part, by inhibition of the β-catenin-c-Myc signaling pathway. These findings suggest that CPX could be a promising antileukemia drug, and modulation of the intracellular ferritin expression might be an effective method in the treatment of ALL. Therefore, integrating CPX into the current GC-containing ALL protocols could lead to the improvement of the outcome of ALL, especially GC-resistant ALL. PMID:27551974

  18. Complex Biological Systems Analysis of Cell Cycling Models in Carcinogenesis: I. The essential roles of modifications in the c-Myc, TP53/p53, p27 and hTERT modules in Cancer Initiation and Progression

    CERN Document Server

    Prisecaru, V I

    2004-01-01

    A new approach to the integration of results from a modular, complex biological systems analysis of nonlinear dynamics in cell cycling network transformations that are leading to carcinogenesis is proposed. Carcinogenesis is a complex process that involves dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compartments that form numerous inter-related pathways referred to as networks. One such network module contains the cell cyclins whose functions are essential to cell cycling and division. Cyclins are proteins that also link to several critical pro-apoptotic and other cell cycling/division components, such as: c-Myc, p27, the tumor suppressor gene TP53 and its product-- the p53 protein with key roles in controlling DNA repair, inducing apoptosis and activating p21 (which can depress cell cyclins if activated), mdm2(with its biosynthesis activated by p53 and also, in its turn, inhibiting p53), p21, the Thomsen-Friedenreich antigen(T- antigen),Rb,Bax, Ba...

  19. Triphala Extract Suppresses Proliferation and Induces Apoptosis in Human Colon Cancer Stem Cells via Suppressing c-Myc/Cyclin D1 and Elevation of Bax/Bcl-2 Ratio

    Directory of Open Access Journals (Sweden)

    Ramakrishna Vadde

    2015-01-01

    Full Text Available Colon cancer is the second leading cause of cancer related deaths in the USA. Cancer stem cells (CSCs have the ability to drive continued expansion of the population of malignant cells. Therefore, strategies that target CSCs could be effective against colon cancer and in reducing the risk of relapse and metastasis. In this study, we evaluated the antiproliferative and proapoptotic effects of triphala, a widely used formulation in Indian traditional medicine, on HCT116 colon cancer cells and human colon cancer stem cells (HCCSCs. The total phenolic content, antioxidant activity, and phytochemical composition (LC-MS-MS of methanol extract of triphala (MET were also measured. We observed that MET contains a variety of phenolics including naringin, quercetin, homoorientin, and isorhamnetin. MET suppressed proliferation independent of p53 status in HCT116 and in HCCSCs. MET also induced p53-independent apoptosis in HCCSCs as indicated by elevated levels of cleaved PARP. Western blotting data suggested that MET suppressed protein levels of c-Myc and cyclin D1, key proteins involved in proliferation, and induced apoptosis through elevation of Bax/Bcl-2 ratio. Furthermore, MET inhibited HCCSCs colony formation, a measure of CSCs self-renewal ability. Anticancer effects of triphala observed in our study warrant future studies to determine its efficacy in vivo.

  20. Radiosensitivity of small-cell lung cancer xenografts compared with activity of c-myc, N-myc, L-myc, c-raf-1 and K-ras proto-oncogenes

    DEFF Research Database (Denmark)

    Rygaard, K; Slebos, R J; Spang-Thomsen, M

    1991-01-01

    Oncogenes of the myc family c-raf-1 and K-ras have been reported to modulate radiosensitivity. We examined the possible relationship between in vivo radiosensitivity to single-dose irradiation with 3-10 Gy, and activity of these proto-oncogenes in 2 sets of small-cell lung cancer (SCLC) xenografts...... expressed identical amounts of c-raf-1 and high levels of c-myc mRNA, but neither expressed N-myc or L-myc. None of the tumours was mutated at codon 12 or K-ras. Our results show that SCLC xenografts with different radiosensitivity may express identical amounts of some of the proto-oncogenes reported...... to modulate radiosensitivity. Thus, factors other than activation of the examined proto-oncogenes must be involved in causing the differences in radiosensitivity found in the SCLC xenografts. Possible long-term effects of irradiation on proto-oncogene expression was examined in xenografts of GLC-16, following...

  1. Detection of gene amplification in MYCN, C-MYC, MYCL1, ERBB2, EGFR, AKT2, and human papilloma virus in samples from cervical smear normal cytology, intraepithelial cervical neoplasia (CIN I, II, III, and cervical cancer

    Directory of Open Access Journals (Sweden)

    Dabeiba Adriana García

    2011-06-01

    Full Text Available Introducción: El cáncer cervical es el segundo cáncer más importante en mujeres a nivel mundial y es la segunda causa de muerte por cáncer en mujeres. Se ha demostrado que el proceso de carcinogénesis cervical presenta componentes tanto genéticos como epigenéticos y medio ambientales. En la actualidad, hay gran interés en la búsqueda de marcadores moleculares asociados con la progresión de esta enfermedad, uno de los posibles mecanismos y que además está poco estudiado en cáncer cervical es la amplificación génica de algunos oncogenes como la familia MYC, EGFR y AKT entre otros. Objetivos: Detectar la amplificación génica de MYCN, C-MYC, MYCL1, ERBB2, EGFR y AKT2 además de la presencia del virus de papiloma humano en cepillados cervicales en mujeres con citología normal o con neoplasia intraepitelial cervical (NIC I, II y III o con cáncer cervical. Métodos: Se genotipificó mediante reverse line blot (RLB el virus de papiloma humano (VPH y se determinó el estado de amplificación génica de los genes mencionados mediante PCR en tiempo real utilizando sondas taqman. Resultados: El VPH se encontró presente en 4% de las pacientes con citología normal, en 48% en NIC I, 63.6% en NIC II, 64% en NIC III y 70.8% en cáncer cervical. Los genes MYCN, MYCL1 y ERBB2 mostraron mayor amplificación en lesiones de alto grado y cáncer con diferencias estadísticamente significativas  a las lesiones de bajo grado y citología normal, en 39.1%, 34.7% y 30.4% respectivamente. Además, se encontraron amplificados los genes C-MYC, EGFR y AKT2, en muestras de pacientes con cáncer cervical, en 12%, 18% y 13% respectivamente. Sin embargo, no se observaron diferencias estadísticamente significativas con respecto a las lesiones de alto y bajo grado y citología normal. Conclusión: En las lesiones de alto grado como en cáncer cervical, se encuentra mayor prevalencia del virus al igual que se detectan mayor cantidad de alteraciones gen

  2. In vitro effects of zinc and folic acid on the expressions of Neurogenin 3, Kruppel-like factor 4, c-Myc, Nanog, Nestin and POU class 5 homeobox 1 genes

    Directory of Open Access Journals (Sweden)

    Zehra Dilsad Coban

    2015-06-01

    Full Text Available Objective: Genes are regulated at multiple levels by using nutritional factors during neurogenesis and gliogenesis in brain development. Folic acid (FAand zinc regulate the expressions of some genes which participate in brain development as nutritional factors. So, we aimed to find the effect of FA and zinc on the expression levels of neurogenin 3 (NGN3, Kruppel-like factor 4 (Klf4, c-Myc, nanog, POU class 5 homeobox 1-Pou5F1 (Oct4, and Nestin in mouse fetal brain tissue in neural plate phase at gestational day 7 (GD7and in fetal brain tissue at GD20. Methods: All the tissues were cultured primarily. FA and zinc solutions were added. Real time-polymerase chain reaction was performed in RNA obtained from in each sample. Results: FA has no effect on GD7 mouse neural plate tissue and GD20 mouse fetal brain tissue. Zinc has no effect on GD7 mouse neural plate tissue. Zinc increased the expressions of NGN3, Klf4, nanog, Nestin, and Oct4 genes on GD20 mouse fetal brain tissue. Conclusion: This in vitro study represents that zinc is important in the expressions of NGN3, Klf4, Nanog, Nestin, and Oct4 genes in the late phase of pregnancy. The stimulator effect of Zinc on the expression levels of these genes may show us the possible role of zinc in fetal brain development in the late phase of pregnancy. [J Exp Integr Med 2015; 5(2.000: 75-80

  3. Hans, Choi immunophenotyping and C-MYC genetic features between pediatric and adult diffuse large B-cell lymphoma%儿童与成人弥漫大B细胞淋巴瘤的Hans、Choi免疫分型和C-MYC基因特征

    Institute of Scientific and Technical Information of China (English)

    徐红艳; 黄慧; 杨文萍; 黄传生; 钟梅慧

    2013-01-01

    Objective To explore the difference of Hans,Choi immunophenotyping and C-MYC gene characteristics between pediatric and adult diffuse large B-cell lymphoma.Methods To collect 60 cases of DLBCL clinicopathological data and follow-up,which contained 17 cases of children group,adult group of 43 patients.To observe CD10,BCL-6,MUM1,FOXP1,GCET1 and CD5 protein expression by immunohistochemical SP method and evaluated by Hans and Choi immunophenotyping standard genotyping.To detect C-MYC gene circumstances by interphase fluorescence insituhybridization (FISH).Results 1) Hans typing:the Children DLBCL group of GCB were 11 cases,non-GCB type were 6 cases; the GCB type in the adult DLBCL group were nine cases,non-GCB type were 34 cases.2)Choi typing:the Children DLBCL group of GCB type were 13 cases,ABC type were 4 cases; the adult DLBCL group of GCB type were 13 cases,ABC type were 30 cases (P < 0.01).3) C-MYC gene:The C-MYC gene disruption of children DLBCL were 5 cases; C-MYC gene in 43 adult cases were normal(P <0.01).Conclusions Child DLBCL of GCB-type with better prognosis while but non-GCB-type predict worse prognosis.The C-MYC gene disruption in Children DLBCL was significantly higher than that of adult ones.%目的 探讨弥漫大B细胞淋巴瘤(DLBCL)各年龄组的Hans、Choi免疫分型及C-MYC基因特征.方法 收集60例DLBCL临床病理资料并进行随访,其中儿童组17例、成人组43例.用免疫组化SP法观察CD10、BCL-6、MUM1、FOXP1、GCET1及CD5蛋白表达,根据Hans及Choi免疫分型标准分型;用间期荧光原位杂交法检测C-MYC 基因.结果 1)Hans分型:儿童DLBCL组GCB型11例,non-GCB型6例;成人组DLBCL中GCB型9例,non-GCB型34例(P<0.05).2) Choi分型:儿童DLBCL组GCB型13例,ABC型4例;成人DLBCL组GCB型13例,ABC型30例(P<0.01).3) C-MYC基因:儿童组DLBCL中C-MYC基因断裂6例;成人组DLBCL中C-MYC基因正常43例(P<0.01).结论 儿童DLBCL以GCB型为主,预后较好;成人DLBCL以non-GCB

  4. Cyclin D1,Cyclin E,c- Myc在涎腺良恶性多形性腺瘤中的表达研究%Expression of Cyclin D1, Cyclin E, C-myc in Benign and Malignant Pleomorphic Adenoma of Salivary Gland

    Institute of Scientific and Technical Information of China (English)

    冯晓洁; 罗欣; 陈洪伟; 温黎明; 程勇

    2011-01-01

    Objective: To study the expressions of cyclin Dl, cyclin E and c-myc in benign and malignant PA, and to learn their association with clinical features and cell proliferation. Methods: SP immunohistochemical staining was applied to detect the expression levels of cyclin Dl,cyclin E and c - myc in 30 benign pleomorphic adenomas ,30 cellular-type pleomorphic adenomas, 30 malignant pleomorphic adenomas, and compared their expression with 30 normal gland tissues of adjacent carcinoma. Results: Cyclin Dl, cyclin E and c-myc expression were significantly higher in PA than in the normal gland tissues of adjacent carcinoma(P<0. 05). And there was no statistic difference for the expression levels of cyclin Dl, cyclin E, c -myc between benign pleomorphic adenoma and cellular-type pleomorphic adenoma. The expression levels of cyclin Dl, cyclin E and c-myc were uncorrelated with sex, recurrence, location, and tumor size. But in malignant pleomorphic adenoma, the expression level of cyclin Dl was correlated with TNM stage and the expression level of cyclin E was correlated with invasion. Conclusion: Together or alone of cyclin Dl, cyclin E and c-myc might be useful molecular biological markers in predicting the formation, development and carcinogenesis of PA. They might be thought as prognostic markers and chemotherapy targets. They might also contribute to classification of pathology diagnosis.%目的:研究cyclin D1,cyclin E,c- myc在涎腺多形性腺瘤中的表达,与临床生物学特性和细胞增殖的关系以及对于涎腺多形性腺瘤病理学诊断的意义.方法:采用免疫组化方法检测30例良性多形性腺瘤,30例细胞丰富型多形性腺瘤和30例恶性多形性腺瘤中cyclin D1、cyclin E、c- myc蛋白的表达水平,并与30例癌旁正常涎腺组织中的表达对比.结果:cyclin D1、cyclin E和c- myc在恶性多形性腺瘤中的阳性表达率明显高于良性和细胞丰富型多形性腺瘤(P<0.05),而三者在良性多形性腺瘤

  5. The research of the influence of Pingyangmycin on c-myc and Ras-P21 protein expression in penile cancer%平阳霉素对阴茎癌组织c-myc及Ras-P21蛋白表达影响的研究

    Institute of Scientific and Technical Information of China (English)

    王志超; 戴洪双; 刘文龙; 李效忠; 乔忠杰

    2014-01-01

    目的:探讨应用平阳霉素化疗对阴茎癌组织蛋白c-myc、Ras-P21表达的影响及意义。方法收集1995—2005年间阴茎鳞状细胞癌患者100例,按照术前是否进行化疗分为两组,其中化疗组50例,术前应用平阳霉素化疗7天,并在化疗后行阴茎部分切除术+改良方法的腹股沟淋巴结清扫术;对照组50例,未进行化疗而直接行阴茎部分切除术改良方法的腹股沟淋巴结清扫术。应用免疫组化法( SP)对两组的100例阴茎癌组织标本进行c-myc、Ras-P21蛋白产物检测。应用χ2检验对数据进行统计分析。结果化疗组50例阴茎癌标本中c-myc、Ras-P21表达阳性率分别为30%、27%。对照组50例阴茎癌标本中,c-myc、Ras-P21表达阳性率分别为52%、48%。经χ2检验,化疗组与对照组的c-myc、Ras-P21表达阳性率的差异具有统计学意义(P<0.05)。结论应用平阳霉素化疗后阴茎癌组织中c-myc、Ras-P21蛋白的表达明显下降。%Objective To evaluate the influence and significance of Pingyangmycin chemotherapy on the c-myc and Ras-P21 protein expression in penile cancer .Methods A total of 100 penile squamous cell carci-noma cases was retrospectively studied and divided into two groups .Data were obtained from 1995 to 2005 .In the chemotherapy group ,50 cases of patients were selected to perform preoperative chemotherapy before surgery .The patients were treated by Pingyangmycin .After 7 times of medication ,partial excision of penis plus improved ingui-nal lymph node dissection was performed .In the control group ,50 cases of patients were selected for partial exci-sion of penis plus improved inguinal lymph node dissection directly without any pre -operative chemotherapy .All pathology specimens were detected of c -myc and Ras-P21 protein expression by immunohistochemical staining assay.Theχ2 test was used for the statistical analysis .Results In

  6. 流体切应力对脑动静脉畸形内皮细胞增殖与c-myc表达的影响%Effect of flow shear stress on endothelial cell proliferation and c-myc expression in cerebral arteriovenous malformation

    Institute of Scientific and Technical Information of China (English)

    赵明光; 李彦兵; 吕博川; 梁勇; 薛洪利; 赵丽萍; 王丹玲

    2007-01-01

    BACKGROUND:Shear stress can directly mediate the expression of endothelial cells, especially some cytokine genes whose codes are related to angiogenesis. Otherwise, flow shear stress of blood plays an importantly biological role in regulating vascular structure and function.OBJECTIVE: To observe the effects of laminar flow shear stress on the proliferation of vascular endothelial cells and the expression of protooncogene c-myc in human cerebral arteriovenous malformation.DESIGN: Randomized controlled study.SETTING: Department of Neurosurgery, Shenyang General Hospital of Military Area Command of Chinese PLA.MATERIALS: The experiment was carried out in the Neuromedical Institute, General Hospital of Shenyang Military Area Command of Chinese PLA from November 2006 to February 2007. Fresh samples of human cerebral arteriovenous malformation were derived from 20 patients who were of grade Spetzler Ⅱ -Ⅲ and received resection of human cerebral arteriovenous malformation in the Department of Neurosurgery, General Hospital of Shenyang Military Area Command of Chinese PLA in 2006. All cases were diagnosed with whole-brain angiography before operation. The main reagents and equipments were detailed as follows: M199 culture media (Gilbco BRL), quality fetal bovine serum (HyClone), endothelial cell growth supplement (ECGS; Sigma, USA), CO2 incubator (Forma Scientific, USA), flow cytometry analysis of cell cycle kit (BD Company), flow cytometer (FACS Calibur, BD Company), rat-anti-human c-myc monoclonal antibody (Santa Cruz Company, USA), and reverse transcription polymerase chain reaction (RT-PCR) kit (Promega).METHODS: Tissue explants adherent method was used to culture vascular endothelial cells of human cerebral arteriovenous malformation, and then the cells were classified into 4 groups based on degree of shear stress, including control group, low shear stress group, moderate shear stress group and high shear stress group. Cultured endothelial cells of human cerebral

  7. Epstein–Barr virus growth-transformed cells are converted to malignancy following transfection of a 1.3-kb CATR1 antisense construct independent of a change in the level of c-myc expression followed by a 8;14 chromosomal translocation

    OpenAIRE

    Li, Dawei; Sun, Xiao Li; Casto, Bruce; Fang, Jin; Theil, Karl; Glaser, Ronald; Milo, George

    1998-01-01

    The AGLCL Epstein–Barr virus (EBV) growth-transformed cell line is incapable of inducing tumors in nude mice. When the cells were transfected with a 1.3-kb CATR1 antisense cDNA construct, progressively growing lymphomas could be induced in nude mice. Chromosome analysis of the parental, transfected, and tumor cells revealed that a chromosomal translocation t(8;14)(q24.1;q32) had occurred in the transfected cells and was retained in cells derived from tumors. Moreover, enhanced c-myc expressio...

  8. In vivo study on the effects of microcystin extracts on the expression profiles of proto-oncogenes (c-fos, c-jun and c-myc) in liver, kidney and testis of male Wistar rats injected i.v. with toxins.

    Science.gov (United States)

    Li, Huiying; Xie, Ping; Li, Guangyu; Hao, Le; Xiong, Qian

    2009-01-01

    Microcystins (MCs) are a potent liver tumor promoter, possessing potent tumor-promoting activity and weak initiating activity. Proto-oncogenes are known to be involved in the tumor-promoting mechanisms of microcystin-LR. However, few data are available on the effects of MCs on proto-oncogenes in the whole animal. To investigate the effects of MCs on the expression profile of the proto-oncogenes in different organs, male Wistar rats were injected intravenously with microcystin extracts at a dose of 86.7 mug MC-LR eq/kg bw (MC-LR eq, MC-LR equivalents). mRNA levels of three proto-oncogenes c-fos, c-jun and c-myc in liver, kidney and testis were analyzed using quantitative real-time PCR at several time points post-injection. Significant induction of these genes at transcriptional level was observed in the three organs. In addition, the increase of mRNA expression of all three genes was much higher in liver than in kidney and testis. Meanwhile, the protein levels of c-Fos and c-Jun were investigated by western blotting. Both proteins were induced in the three organs. However, elevations of protein levels were much lower than those of mRNA levels. These findings suggest that the expression of c-fos, c-jun and c-myc might be one possible mechanism for the tumor-promoting activity and initiating activity of microcystins.

  9. 伽玛射线诱导脑膜瘤细胞凋亡和影响原癌基因c-myc的表达%Effects of gamma-ray on apoptosis and expression of c-myc protooncogene of meningioma cells

    Institute of Scientific and Technical Information of China (English)

    陈春美; 陈建乐; 韦浩; 张伟强; 蔡刚峰; 王春华; 王锐; 石松生; 杨卫忠

    2013-01-01

    目的 观察不同剂量伽玛(γ)射线诱导脑膜瘤细胞凋亡和原癌基因c-myc表达变化.方法 采用机械分离法获得稳定生长脑膜瘤细胞的离体培养细胞株,根据不同照射剂量分为4组,照射组分别接受中心剂量为2.00、5.00、8.22、13.33 Gy,设立对照组,剂量为0,照射后荧光显微镜观察细胞形态变化,流式细胞术检测细胞周期和凋亡率,Westem blot法检测c-myc蛋白的表达变化.结果 对照组、照射1组、2组、3组及4组细胞凋亡率分别为:(3.73±0.25)%、(4.07±0.29)%、(9.81±1.66)%、(21.63±3.08)%、(8.27±1.61)%;c-myc蛋白表达分别为:0、11±0.01、0.12±0.01、0.19 ±0.02、0.31±0.08、0.09±0.01;对照组和中心剂量2 Gy组照射后细胞形态、细胞周期、凋亡率和c-myc蛋白表达差异无统计学意义(P>0.05);中心剂量分别为5.00 Gy和8.22 Gy组细胞出现凋亡特征,细胞周期G0/G1和G2/M期细胞数量逐渐增多,细胞凋亡率升高,c-myc蛋白表达增多,与对照组比较差异均有统计学意义(P<0.05);剂量为13.33 Gy组,细胞以坏死为主,S期细胞增多,c-myc蛋白表达减少.结论 一定剂量的伽玛刀射线能够诱导脑膜瘤细胞进入凋亡,原癌基因c-myc在此过程中可能发挥促进脑膜瘤细胞进入凋亡过程.%Objective To investigate the apoptosis of meningioma cell and changes of the expression of c-myc protooncogene after gama ray radiation.Methods The isolated and cultured meningioma cells with stable growth were obtained from a patient with meningiomas by mechanical separation,and those cells were divided into 4 groups with the radiation center doses of 2.00,5.00,8.22,and 13.33 Gy respectively.There was a control group without radiation.Meningioma cell morphology was observed under fluorescent microscope.Flow cytometry was used to examine the cell cycle and apoptosis.The expression of c-myc protein was detected by using Western blotting.Results The cell apoptosis rate in

  10. Expression of c-Myc in Pulmonary Vascular Smooth Muscle Cells in the Development of Pulmonary Vascular Remodeling in Broilers Induced by Low Ambient Temperature%低温诱发肉鸡肺血管重塑过程中肺动脉平滑肌细胞c-Myc蛋白表达的变化

    Institute of Scientific and Technical Information of China (English)

    王建琳; 尹燕博

    2011-01-01

    The study was conducted to assess the expression of c-Myc in pulmonary vascular smooth muscle cells in the development of pulmonary vascular remodeling in broilers induced by low ambient temperature. 120 male broiler chicks (Arbor Acre) of commercial strain were randomly allocated to control group (raised at the temperature of (22 + 1. 5) °C ) and low temperature group (raised at the temperature of (11 + 2) °C) at 15 days old. Six broilers in each group were sampled every week from 15 to 50 days of age and lungs were paraffin-embedded, sectioned. The percentage of relative medial thickness (MT%) and the percentage of relative lumen area (RLA%) ,the indexes of pulmonary vascular remodeling,were examined by computer-image analyzing system. Positive indexes (PI) of c-Myc in pulmonary vascular smooth muscle cells were assessed. The result indicated that pulmonary vascular remodeling were significantly elevated in low temperature group from 36 days of age (P<0. 01 or P<0. 05). PI of c-Myc in pulmonary vascular smooth muscle cells were significantly higher than those in the control group from 29 days of age (P<0. 01). The study demonstrated that c-Myc in pulmonary vascular smooth muscle cells were expressed significantly induced by low ambient temperature and have a pivotal role in the development of pulmonary vascular remodeling.%试验旨在研究环境低温诱发肉鸡肺血管重塑过程中肺小动脉血管平滑肌细胞c-Myc蛋白的表达变化,初步探讨肉鸡肺血管重塑的发生机制.120只雄性AA商品代肉鸡15日龄时随机分为对照组((22±1.5)℃)条件下饲养)和低温组((11±2)℃条件下饲养).15~50日龄,每周每组随机取6只,取肺组织做石蜡切片,Weigert-间苯二酚复红染色,观察并测定m管重塑情况;采用免疫组织化学方法榆测肺动脉血管平滑肌细胞c-Myc蛋白表达,并对其进行半定量化.结果显示:(1)低温组肉鸡肺小动脉结构从36日龄开始较对照

  11. Quercetin通过TGF-β1/smad3/c-myc信号通路对LOVO细胞增殖的抑制作用%Quercetin inhibits proliferation of LOVO cells through TGF-β1/smad3 / c-myc signaling pathway

    Institute of Scientific and Technical Information of China (English)

    安昌勇; 寇耀; 赵林; 邵新宏; 张刘平; 张才全

    2013-01-01

    Objective To investigate the effect of Quercetin on TlGF-βl/smad3/c-myc signating pamway of LO V O cell strain as well as the possible mechanisms of inhibitory effect of Quercetin on the proliferation of LOVO cells.Methods Lovo ceils were treated with Quercetin at dosages of 5,10,20,40,80 and 160 μmol / L for 48 h respectively,using those untreated as control,and determined for proliferation activity.LOVO cells were divided into C,T,TQ and Q groups.The cells in C group were untreated,while those in T group were treated with 5 ng/ml TGF-β1 for one week,those in TQ group with 5 ng/ml TGF-β1 for one week then with 20 μmol/L Quercetin for 72 h,and those in Q group with 20 μmol/L Quercetin for 72 h.The effects of Quercetin and TGF-β1 on the clone formation ability as well as expressions of smad3 and c-myc were analyzed by plate clone formation test,immunohistochemical assay with SP staining,RT-PCR and Western blot.Results Quercetin showed significantly dosage-dependent inhibitory effect on proliferation of LOVO cells,with an IC50 of about 40 μmol/L.The proliferation of LOVO cells as well as expressions of smad3 and c-myc were promoted by TGF-β1 significantly (P < O.05),while were inhibited by Quercetin significantly (P < 0.05).As compared with those in TQ group,both the proliferation ability and the expression level of c-myc in TQ group decreased significantly(P < 0.05).Conclusion Quercetin down-regulated the expression of target gene c-myc by inhibiting the TGF-β1/smad3/c-myc signaling pathway,and inhibited the proliferation of LOVO cells.%目的 研究Quercetin对结肠癌LOVO细胞株TGF-β1/smad3/c-myc信号通路的影响,并探讨其抑制LOVO细胞增殖的可能机制.方法 采用5、10、20、40、80、160 μmol/L的Quercetin处理结肠癌LOVO细胞48 h,以未经Quercetin处理的LOVO细胞作为对照组,采用MTT法检测Quercetin对细胞增殖活力的影响.以5 ng/ml的TGF-Bl刺激l周的LOVO细胞为细胞模型,设对照

  12. Clinical significance of bcl-6, p53, c-myc aberrations in diffuse large B-cell lymphoma%bcl-6、p53、c-myc基因异常在弥漫大B细胞淋巴瘤中的临床意义

    Institute of Scientific and Technical Information of China (English)

    何兰兰; 严峰; 刘德亮; 曹祥山; 谢晓宝; 王志林

    2013-01-01

    Objective To investigate aberrations of bcl-6,p53,c-myc genes in diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods Interphase fluorescence in situ hybridization (I-FISH) was detected in 59 DLBCL patients in vivo tissue bcl-6,p53 protein,c-myc gene status.The patients were treated with CHOP or R-CHOP chemotheralpy,and the survival rates and treatment efficiency were compared.Results The p53 deletion was detected in 18 of the 59 cases (30.5 %),bcl-6 rearrangement in 11 cases (18.6 %),5 cases with c-myc rearrangement (8.5 %).In the aspects of remission rate,p53 deletion positive group contained less advantage than negative ones (33.3 % vs 75.6 %,x2 =9.560,P =0.002).The prognosis of bcl-6 gene rearrangement positive group different from negative group,but the difference was not statistically significant (OS,P =0.107; PFS,P =0.094),p53 deletion positive patients was in significantly worse prognosis than the negative group (OS,P =0.031; PFS,P =0.028),c-myc rearrangement positive group difference in gene rearrangement negative group,but the difference was not statistically significant (OS,P =0.163; PFS,P =0.167).In the CHOP group,prognosis of p53 deletion,c-myc rearrangement positive group were significantly worse than the negative group,the difference was statistically significant (P < 0.05).In R-CHOP group,the prognostic significance of bcl-6 gene rearrangement positive group were worse (OS,P =0.003; PFS,P =0.007).Conclusion DLBCL patients with bcl-6,p53,c-myc genes aberrations are related with poor prognosis,and they can be used as prognostic factors for predicting DLBCL and guiding therapy.%目的 探讨bcl-6 、p53、c-myc基因异常的检测在弥漫大B细胞淋巴瘤(DLBCL)中的临床意义.方法 间期荧光原位杂交(I-FISH)方法检测59例DLBCL患者活体石蜡组织bcl-6、p53蛋白、c-myc基因异常的情况,同时以CHOP及R-CHOP方案化疗,评价疗效.观察bcl-6、p53蛋白、c-myc基因与化疗疗

  13. Research of influence of Pingyangmycin neoajuvant chemotherapy on c-myc, Ras-P21, and P53 protein expression in penile cancer%平阳霉素新辅助化疗对阴茎癌组织c-myc、Ras-P21、P53蛋白表达影响的研究

    Institute of Scientific and Technical Information of China (English)

    徐磊; 刘文龙; 王志超; 乔忠杰

    2014-01-01

    Objective To evaluate the influence and significance of Pingyangmycin neoajuvant chemotherapy on the c-myc, Ras-P21 and P53 protein expression in penile cancer on. Methods The Data of 100 patiens with penile squamous cell carcinoma were obtained in the Department of Urology, the Tumor Hospital of Harbin Medical University, from 1995 to 2005, and they were divided into two groups according to whether given the neoajuvant chemotherapy before the surgery or not. 50 patients in the neoajuvant group were given Pingyangmycin preoperative chemotherapy for 7 days before surgery, after the chemotherapy, partial excision of penis plus improved inguinal lymph node dissection was per-formed. 50 patients in the control group were given partial excision of penis plus improved inguinal lymph node dissec-tion directly without any pre-operative chemotherapy. All pathology specimens were detected of c-myc, Ras-P21, P53 protein product expression by immunohistochemical staining assay. Results In neoajuvant chemotherapy group, the pos-itive expression rates of c-myc, Ras-P21, P53 were 30%, 27%, 23%,respectively. While in control group, the positive expression rates of c-myc, Ras-P21, P53 were 52%, 48%, 50%, the differences were statistically significant (P<0.05). Conclusion The c-myc, Ras-P21, P53 protein expressions are significantly decreased in the tissue of Pingyangmycin neoajuvant chemotherapy of penile cancer, Pingyangmycin neoajuvant chemotherapy may decrease the degree of malig-nancy of penile cancer.%目的:探讨应用平阳霉素新辅助化疗对阴茎癌组织基因蛋白c-myc、Ras-P21、P53表达的影响及意义。方法收集哈尔滨医科大学附属肿瘤医院泌尿外科1995~2005年罹患阴茎鳞状细胞癌的住院患者100例,按照术前是否进行辅助化疗分为两组,其中新辅助化疗组50例,术前应用平阳霉素化疗7 d,化疗后行阴茎部分切除术,并行双侧腹股沟淋巴结改良清扫术;对照组50例,直接行

  14. 通脉汤方对实验性动脉粥样硬化家兔胸主动脉表皮生长因子受体和c-myc基因表达的影响%Effect of Tongmai Recipe on Epidermal Growth Factor Receptor and Protooncogene c-myc mRNA Expression in Aorta of Atherosclerotic Rabbit

    Institute of Scientific and Technical Information of China (English)

    张娟; 孙明; 周宏研

    2007-01-01

    目的 探讨通脉方对实验性动脉粥样硬化家兔胸主动脉表皮生长因子受体和c-myc基因表达的影响.方法 日本大耳白兔40只,随机分为4组:①对照组10只,以普通饲料喂养,每日两次;②模型组10只,以高胆固醇饲料[胆固醇0.5 g/(kg·d)、蛋黄2 g/(kg·d)和猪油2 g/(kg·d)]喂养,每日两次;③通脉汤方低剂量组(简称低剂量组)10只,高胆固醇饲料喂养(剂量同模型组),同时予通脉汤方灌胃,每只剂量相当于生药7.3 g/(kg*d),分上下午两次给药;④通脉汤方高剂量组(简称高剂量组)10只,高胆固醇饲料喂养(剂量同模型组),同时予通脉汤方灌胃,每只剂量相当于生药21.9 g/(kg·d),分上下午两次给药;共喂养16周.运用免疫组织化学染色法检测主动脉表皮生长因子受体的表达,同时用内参比逆转录聚合酶链反应定量分析c-myc mRNA在主动脉的表达.结果 模型组主动脉表皮生长因子受体及c-myc mRNA表达显著高于对照组(分别为0.327±0.030比0.209±0.006,P0.05;0.44±0.09比0.52±0.11 P>0.05).结论 ①动脉粥样硬化时促进血管平滑肌细胞增殖的表皮生长因子受体及原癌基因c-myc mRNA表达增强.②通脉汤方通过抑制血管壁表皮生长因子受体及c-myc基因的表达,从而抑制血管平滑肌细胞增殖.

  15. 跑台运动训练对脑缺血损伤大鼠热休克蛋白70及C-MYC表达的影响%Effects of treadmill training on the expression of HSP70 and C-MYC in the brains of rats with focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    刘德山; 刘楠; 张逸仙; 杜厚伟; 陈荣华

    2010-01-01

    目的 探讨跑台运动训练对局灶性脑缺血大鼠神经功能恢复和脑缺血组织中热休克蛋白70(HSP70)及C-MYC表达的影响.方法 将42只清洁级成年雄性SD大鼠分为假手术组6只、模型组18只、运动组18只.模型组、运动组大鼠采用改良的Longs线栓法制备大脑中动脉闭塞(MCAO)脑缺血模型,运动组于造模成功后24 h采用跑台训练器进行运动训练,每周6 d,共2周,其余2组则置于普通笼内饲养,期间可自由活动、进食.采用修正的神经行为学评分方法评价模型组和运动组大鼠MCAO脑缺血后第3,7,14天的神经功能,并断头取脑,采用逆转录-多聚酶链反应(RT-PCR)法、免疫组织化学和Western blot法检测脑缺血组织中HSP70、C-MYC的表达.结果 运动组大鼠脑缺血第7,14天神经功能评分均明显优于模型组(P<0.05或0.01);运动组大鼠脑缺血第7,14天HSF70和C-MYC表达较模型组增强(P<0.05或0.01).结论 运动训练可促进脑缺血大鼠神经功能恢复,其机制可能与上调脑缺血组织中HSP70及C-MYC表达有关.%Objective To observe the effects of treadmill training on the recovery of neurological function and the expression of HSP70 and C-MYC in the brains of rats with focal cerebral ischemia. Methods Forty-two male adult Sprague-Dawley rats were randomly divided into a sham group ( n =6), a model group (n =18) and a treadmill exercise group (n=18). Focal cerebral ischemia was induced by right middle cerebral artery occlusion (MCAO) in the model group and exercise group using a modified version of Longa's method. The rats in the treadmill exercise group were given treadmill training 6 d per week for 2 weeks after 24 h of MCAO. By contrast, the rats in the sham group and the model group were reared in standard cages. Before the rats were sacrificed at the 3rd, 7th and 14th d after MCAO, their neurological functions were tested using modified neurological severity scores ( mNSS) , and the mRNA and

  16. c-myc、p53和p16的表达及GNAS1基因突变在骨的纤维结构不良中的意义%Abnormal expression of c-myc,p53,p16 protein and GNAS1 gene mutation in fibrous dysplasia

    Institute of Scientific and Technical Information of China (English)

    唐娟; 赵红叶; 郑莉; 张惠箴; 蒋智铭

    2009-01-01

    Objective To study the significance of c-myc,p53 and p16 protein expression in fibrous dysplasia,to detect the GNAS1 gene mutation in fibrous dysplasia,and to explore the property of fibrous dysplasia.Methods The expression of c-myc,p53 and p16 protein was evaluated by immunohistochemistry SP method in 35 cases of fibrous dysplasia including 1 FD with malignancy,1 Mazabraud syndrome and 20 control cases (10 cases of bony callus,10 cases of osteosarcoma). Genomic DNA extraction,PCR amplification and gene sequencing were used to detect GNAS1 gene mutation in 35 cases of fibrous dysplasia.Results C-myc protein immunoreactivity was detected in 91 percentage of FD(P=0.001).Compared with the negative control group,the difference was significant.P16 positive waa detected in 34 FD cases(P=0.001).The difference was significant as compared with the positive control group.Positive p53 protein expression was detected in the only 1 case of fibrous dysplasia with malignant transformation.PCR amplification was successful in 12 of 35 FD cases.Two of the 12 FD cases were detected to have GNAS1 gene mutation,in which 1 case waa FD of Mazabraud syndrome,1 case was a monostotic lesion.Concimiom C-myc could be another protooncogene in addition to c-fos in the fibrous dysplasia disease.P53 protein overexpression could be useful in the diagnosis of FD malignancy and in the prediction of the prognosis of FD.The abnormal expression of the gene p16 might play an important role in the formation of FD.The GNAS1 mutation exist in FD.All of the results indicate that FD could be a neoplasia disease.caused by multiple factors leading to a dysfunction of bone development.%目的 检测c-myc、p53和p16蛋白在骨的纤维结构不良(FD)中的表达及其意义,检测FD中GNAS1基因第8外显子突变,探讨FD的病变性质.方法 采用免疫组织化学SP法检测35例FD(包括1例FD恶变,1例Mazabraud综合征)及20例对照组(10例骨痂、10例骨肉瘤)中c-myc、p53和p16蛋白表达.

  17. Role of arsenic trioxide induced apoptosis in Burkitt lymphoma cell line Raji and influence on C-myc expression%三氧化二砷对Burkitt淋巴瘤细胞株Raji凋亡的诱导作用及C-myc表达的影响

    Institute of Scientific and Technical Information of China (English)

    张继青; 钟雷; 李进娥

    2015-01-01

    目的 探讨三氧化二砷(As2O3)对Burkitt淋巴瘤细胞袜Raji凋亡的诱导作用及C-myc表这的影响.方法 通过噻唑蓝比色法检测观察As2 O3对Raji细胞增殖的影响,流式细胞仪观察As2O3对Raji细胞凋亡的诱导作用,逆转录聚合酶链式反应(RT-PCR)法检测As2O3对C-myc mRNA表达的影响.结果 As2O3对Raji细胞生长有抑制作用,呈剂量和时间依赖关系(P<0.01);As2O3对Raji细胞有诱导凋亡作用,呈剂量和时间依赖关系(P<0.01);随着As2O3浓度升高,C-myc的表达水平明显下降(P<0.01).结论 As2O3对Burkitt淋巴瘤细胞株Raji具有增殖抑制和诱导凋亡作用,其作用机制可能与C-myc表达水平明显下降有关.

  18. Extracellular simian virus 40 induces an ERK/MAP kinase-independent signalling pathway that activates primary response genes and promotes virus entry.

    Science.gov (United States)

    Dangoria, N S; Breau, W C; Anderson, H A; Cishek, D M; Norkin, L C

    1996-09-01

    Simian virus 40 (SV40) binding to growth-arrested cells activated an intracellular signalling pathway that induced the up-regulation of the primary response genes c-myc, c-jun and c-sis within 30 min and of JE within 90 min. The up-regulation of the primary response genes occurred in the presence of cycloheximide and when UV-inactivated SV40 was adsorbed to cells. SV40 binding did not activate Raf or mitogen-activated protein kinase (MAP/ERK1), or mobilize intracellular Ca2+. The SV40-induced up-regulation of c-myc and c-jun was blocked by the tyrosine kinase inhibitor, genistein, and by the protein kinase C (PKC) inhibitor, calphostin C, but not by expression of the MAP kinase-specific phosphatase, MKP-1. These results suggest that the SV40-induced signalling pathway includes the activities of a tyrosine kinase and a Ca(2+)-independent isoform of PKC, but not of Raf or MAP kinase. Finally, SV40 infectious entry into cells was specifically and reversibly blocked by genistein.

  19. Wnt signaling and c-Myc in intestinal epithelium

    OpenAIRE

    Muncan, V.

    2007-01-01

    constantly produce cells from a stem cell reservoir that give rise to proliferating transit amplifying cells, which subsequently differentiate and are positioned in their proper compartments. This process has to be under stringent control to ensure life-long tissue homeostasis. It has now become clear that the same signaling pathways that are important during embryonic development control selfreneving tissues. Canonical Wnt signaling plays a key role in regulating intestinal tissue homeostasi...

  20. The value of infection of HR-HPV and the expression of C-MYC in the diagnosis of cervical lesions%高危型HPV感染与C-MYC基因检测在宫颈病变诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    郭宏亮; 黄荣芳; 方丽萍

    2016-01-01

    目的 检测人髓细胞增生原癌基因(myelocytomatosis oncogene,C-MYC)表达及高危型人乳头瘤病毒(High-Riskhuman papilloma virus,HR-HPV)的感染情况,探讨它们在宫颈病变筛查和诊断中的应用价值.方法 选取2010年10月-2011年12月在昆明市妇幼保健院门诊就诊或入院自愿做宫颈癌筛查的患者1 200例,每位患者均行LCT和HC2-HPV检测.LCT剩余标本用荧光原位杂交(FISH)方法检测宫颈脱落细胞中C-MYC基因表达.任一结果阳性者取宫颈活检,最终取宫颈活检患者150例.以病理组织学结果为诊断金标准,将患者分为正常组32例、低度宫颈上皮内瘤变(CIN Ⅰ)组38例、高度宫颈上皮内瘤变(CINⅡ/CINⅢ)组66例、宫颈浸润癌(ICC)组14例.结果 ①在正常组,CIN Ⅰ,CINⅡ/CINⅢ,ICC组,C-MYC基因的表达率分别为3.12%、47.37%、56.06%、92.86%,各组间比较差异有统计学意义(P<0.05).②在正常组,CIN Ⅰ,CINⅡ/CINⅢ,ICC组,HR-HPV的检出率分别为31.25%、65.79%、90.90%、92.86%,正常组与宫颈病变各组间比较差异有统计学意义(P<0.05).CINⅡ/CINⅢ,ICC组HR-HPV的检出率明显高于CIN Ⅰ组(P<0.05).③C-MYC基因检测特异度高,但灵敏度低;而HR-HPV感染检测灵敏度高,但特异度低.④随着病理组织学病变程度加重,C-MYC基因阳性扩增和HC2-HPV阳性率均有不同程度的上升,且二者呈正相关(r=0.456,P=0.000).结论 ①C-MYC基因在CIN Ⅰ,CINⅡ/CINⅢ,ICC组异常表达,且随着病变程度的增加阳性率也增加,特异度高,可能成为宫颈癌癌前病变的生物遗传学检测指标,并有望成为宫颈癌早期筛查方法;②HC2检测HR-HPV是一种有效的宫颈病变的管理手段,可以提高宫颈病变筛查的灵敏度,但是特异度有所降低;③C-MYC基因异常扩增和HPV感染在宫颈癌的发生发展过程中有着密切的关系.

  1. Mapping out Map Libraries

    Directory of Open Access Journals (Sweden)

    Ferjan Ormeling

    2008-09-01

    Full Text Available Discussing the requirements for map data quality, map users and their library/archives environment, the paper focuses on the metadata the user would need for a correct and efficient interpretation of the map data. For such a correct interpretation, knowledge of the rules and guidelines according to which the topographers/cartographers work (such as the kind of data categories to be collected, and the degree to which these rules and guidelines were indeed followed are essential. This is not only valid for the old maps stored in our libraries and archives, but perhaps even more so for the new digital files as the format in which we now have to access our geospatial data. As this would be too much to ask from map librarians/curators, some sort of web 2.0 environment is sought where comments about data quality, completeness and up-to-dateness from knowledgeable map users regarding the specific maps or map series studied can be collected and tagged to scanned versions of these maps on the web. In order not to be subject to the same disadvantages as Wikipedia, where the ‘communis opinio’ rather than scholarship, seems to be decisive, some checking by map curators of this tagged map use information would still be needed. Cooperation between map curators and the International Cartographic Association ( ICA map and spatial data use commission to this end is suggested.

  2. Chromosomal mapping of specific DNA gains and losses in solid tumors using comparative genomic hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Schrock, E.; Manoir, S. du; Speicher, M. [National Center for Human Genome Research, Bethesda, MD (United States)] [and others

    1994-09-01

    Comparative genomic hybridization (CGH) is a new molecular cytogenetic technique that is based on two color FISH and quantitative digital imaging microscopy. CGH is used to comprehensively survey tumor genomes for copy number changes and to determine the map position of amplification sites on normal reference chromosomes. CGH was used to analyze 107 different solid tumors, including 16 low grade astrocytomas, 15 recurrent astrocytic tumors, 13 high grade astrocytomas, 13 small cell lung cancers (SCLC), 14 breast cancer samples (7 diploid and 7 aneupoid tumors), 18 chromophobe renal cell carcinomas and 5 seminomas. Tumor DNA was extracted from frozen tissue, autopic material and formalin fixed, paraffin-embedded tissue samples. Our results revealed tumor specific gains and losses of certain chromosomes or chromosomal subregions (e.g., chromosomes 7 and 10 in glioblastomas, chromosomes 3 and 5 in SCLC). Numerous DNA-amplifications were mapped on reference metaphase and prometaphase chromosomes. The frequent amplification of the EGFR gene (malignant gliomas), protooncogenes of the myc family (SCLC) and of c-myc, int-2 and c-erbB2 (breast cancer) was confirmed. Many additional amplification sites, however, were mapped that were not described before. The results of CGH analysis were independently confirmed by means of cytogenetic banding analysis, interphase cytogenetics with region specific DNA-clones, Southern-Blot analysis, DNA-cytometry and studies of loss of heterozygosity.

  3. Planetary maps

    Science.gov (United States)

    ,

    1992-01-01

    An important goal of the USGS planetary mapping program is to systematically map the geology of the Moon, Mars, Venus, and Mercury, and the satellites of the outer planets. These geologic maps are published in the USGS Miscellaneous Investigations (I) Series. Planetary maps on sale at the USGS include shaded-relief maps, topographic maps, geologic maps, and controlled photomosaics. Controlled photomosaics are assembled from two or more photographs or images using a network of points of known latitude and longitude. The images used for most of these planetary maps are electronic images, obtained from orbiting television cameras, various optical-mechanical systems. Photographic film was only used to map Earth's Moon.

  4. Targeted deletion of multiple CTCF-binding elements in the human C-MYC gene reveals a requirement for CTCF in C-MYC expression.

    Directory of Open Access Journals (Sweden)

    Wendy M Gombert

    Full Text Available BACKGROUND: Insulators and domain boundaries both shield genes from adjacent enhancers and inhibit intrusion of heterochromatin into transgenes. Previous studies examined the functional mechanism of the MYC insulator element MINE and its CTCF binding sites in the context of transgenes that were randomly inserted into the genome by transfection. However, the contribution of CTCF binding sites to both gene regulation and maintenance of chromatin has not been tested at the endogenous MYC gene. METHODOLOGY/PRINCIPAL FINDINGS: To determine the impact of CTCF binding on MYC expression, a series of mutant human chromosomal alleles was prepared in homologous recombination-efficient DT40 cells and individually transferred by microcell fusion into murine cells. Functional tests reported here reveal that deletion of CTCF binding elements within the MINE does not impact the capacity of this locus to correctly organize an 'accessible' open chromatin domain, suggesting that these sites are not essential for the formation of a competent, transcriptionally active locus. Moreover, deletion of the CTCF site at the MYC P2 promoter reduces transcription but does not affect promoter acetylation or serum-inducible transcription. Importantly, removal of either CTCF site leads to DNA methylation of flanking sequences, thereby contributing to progressive loss of transcriptional activity. CONCLUSIONS: These findings collectively demonstrate that CTCF-binding at the human MYC locus does not repress transcriptional activity but is required for protection from DNA methylation.

  5. Map Projection

    CERN Document Server

    Ghaderpour, Ebrahim

    2014-01-01

    In this paper, we introduce some known map projections from a model of the Earth to a flat sheet of paper or map and derive the plotting equations for these projections. The first fundamental form and the Gaussian fundamental quantities are defined and applied to obtain the plotting equations and distortions in length, shape and size for some of these map projections.

  6. Harmonic Maps and Biharmonic Maps

    OpenAIRE

    Hajime Urakawa

    2015-01-01

    This is a survey on harmonic maps and biharmonic maps into (1) Riemannian manifolds of non-positive curvature, (2) compact Lie groups or (3) compact symmetric spaces, based mainly on my recent works on these topics.

  7. Pokemon,c-myc and breast tumor%Pokemon、c-myc与乳腺肿瘤

    Institute of Scientific and Technical Information of China (English)

    付朝江; 崔明

    2009-01-01

    Pokemon(POK erythroid ontogenic factor)蛋白,即POK红系髓性致癌因子,是POK转录抑制物家族的一个成员,为ZBTB7基因所编码的产物.Pokemon蛋白作为转录因子参与一些细胞基因转录的调节,并在细胞分化过程中发挥着关键、多效性的功能.近来发现,Pokemon和c-myc在乳腺肿瘤致癌转化过程中发挥着至关重要的作用,并与乳腺肿瘤的发生密切相关.c-myc原癌基因编码核内DNA结合蛋白,调节其它基因的转录.其基因、mRNA及编码蛋白在多种肿瘤组织中均有异常.c-myc蛋白主要是通过促进cychnE/CDK2复合物的活性来调控G1期细胞进程的.

  8. Causal mapping

    DEFF Research Database (Denmark)

    Rasmussen, Lauge Baungaard

    2006-01-01

    The lecture note explains how to use the causal mapping method as well as the theoretical framework aoosciated to the method......The lecture note explains how to use the causal mapping method as well as the theoretical framework aoosciated to the method...

  9. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    . In particular, mapping environmental damage, endangered species, and human made disasters has become one of the focal point of affective knowledge production. These ‘more-than-humangeographies’ practices include notions of species, space and territory, and movement towards a new political ecology. This type...... of environmental knowledge production. It uses InfoAmazonia, the databased platform on Amazon rainforests, as an example of affective geo-visualization within information mapping that enhances embodiment in the experience of the information. Amazonia is defined as a digitally created affective (map)space within...

  10. Mapping Biodiversity.

    Science.gov (United States)

    World Wildlife Fund, Washington, DC.

    This document features a lesson plan that examines how maps help scientists protect biodiversity and how plants and animals are adapted to specific ecoregions by comparing biome, ecoregion, and habitat. Samples of instruction and assessment are included. (KHR)

  11. Rethinking maps

    OpenAIRE

    Kitchin, Rob; Dodge, Martin

    2007-01-01

    In this paper we argue that cartography is profitably conceived as a processual, rather than representational, science. Building on recent analysis concerning the philosophical underpinnings of cartography we question the ontological security of maps, contending that it is productive to rethink cartography as ontogenetic in nature; that is maps emerge through practices and have no secure ontological status. Drawing on the concepts of transduction and technicity we contend that ...

  12. Mapping Deeply

    Directory of Open Access Journals (Sweden)

    Denis Wood

    2015-08-01

    Full Text Available This is a description of an avant la lettre deep mapping project carried out by a geographer and a number of landscape architecture students in the early 1980s. Although humanists seem to take the “mapping” in deep mapping more metaphorically than cartographically, in this neighborhood mapping project, the mapmaking was taken literally, with the goal of producing an atlas of the neighborhood. In this, the neighborhood was construed as a transformer, turning the stuff of the world (gas, water, electricity into the stuff of individual lives (sidewalk graffiti, wind chimes, barking dogs, and vice versa. Maps in the central transformer section of the atlas were to have charted this process in action, as in one showing the route of an individual newspaper into the neighborhood, then through the neighborhood to a home, and finally, as trash, out of the neighborhood in a garbage truck; though few of these had been completed when the project concluded in 1986. Resurrected in 1998 in an episode on Ira Glass’ This American Life, the atlas was finally published, as Everything Sings: Maps for a Narrative Atlas, in 2010 (and an expanded edition in 2013.

  13. Parametric mapping

    Science.gov (United States)

    Branch, Allan C.

    1998-01-01

    Parametric mapping (PM) lies midway between older and proven artificial landmark based guidance systems and yet to be realized vision based guidance systems. It is a simple yet effective natural landmark recognition system offering freedom from the need for enhancements to the environment. Development of PM systems can be inexpensive and rapid and they are starting to appear in commercial and industrial applications. Together with a description of the structural framework developed to generically describe robot mobility, this paper illustrates clearly the parts of any mobile robot navigation and guidance system and their interrelationships. Among other things, the importance of the richness of the reference map, and not necessarily the sensor map, is introduced, the benefits of dynamic path planners to alleviate the need for separate object avoidance, and the independence of the PM system to the type of sensor input is shown.

  14. CALS Mapping

    DEFF Research Database (Denmark)

    Collin, Ib; Nielsen, Povl Holm; Larsen, Michael Holm

    1998-01-01

    To enhance the industrial applications of CALS, CALS Center Danmark has developed a cost efficient and transparent assessment, CALS Mapping, to uncover the potential of CALS - primarily dedicated to small and medium sized enterprises. The idea behind CALS Mapping is that the CALS State...... of the enterprise is compared with a Reference Enterprise Model (REM). The REM is a CALS idealised enterprise providing full product support throughout the extended enterprise and containing different manufacturing aspects, e.g. component industry, process industry, and one-piece production. This CALS idealised...... enterprise is, when applied in a given organisation modified with respect to the industry regarded, hence irrelevant measure parameters are eliminated to avoid redundancy. This assessment of CALS Mapping, quantify the CALS potential of an organisation with the purpose of providing decision support to the top...

  15. Mapping Resilience

    DEFF Research Database (Denmark)

    Carruth, Susan

    2015-01-01

    relationship between resilience and energy planning, suggesting that planning in, and with, time is a core necessity in this domain. It then reviews four examples of graphically mapping with time, highlighting some of the key challenges, before tentatively proposing a graphical language to be employed by...

  16. Mole Mapping.

    Science.gov (United States)

    Crippen, Kent J.; Curtright, Robert D.; Brooks, David W.

    2000-01-01

    The abstract nature of the mole and its applications to problem solving make learning the concept difficult for students, and teaching the concept challenging for teachers. Presents activities that use concept maps and graphing calculators as tools for solving mole problems. (ASK)

  17. Mapping filmmaking

    DEFF Research Database (Denmark)

    Gilje, Øystein; Frølunde, Lisbeth; Lindstrand, Fredrik;

    2010-01-01

    This chapter concerns mapping patterns in regards to how young filmmakers (age 15 – 20) in the Scandinavian countries learn about filmmaking. To uncover the patterns, we present portraits of four young filmmakers who participated in the Scandinavian research project Making a filmmaker. The focus ...

  18. Participatory maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    looks at computer-assisted cartography as part of environmental knowledge production. It uses InfoAmazonia, the databased platform on Amazon rainforests, as an example of affective geo-visualization within information mapping that enhances embodiment in the experience of the information. Amazonia...

  19. Energetic map

    International Nuclear Information System (INIS)

    This report explains the energetic map of Uruguay as well as the different systems that delimits political frontiers in the region. The electrical system importance is due to the electricity, oil and derived , natural gas, potential study, biofuels, wind and solar energy

  20. MAPPING INNOVATION

    DEFF Research Database (Denmark)

    Thuesen, Christian Langhoff; Koch, Christian

    2011-01-01

    By adopting a theoretical framework from strategic niche management research (SNM) this paper presents an analysis of the innovation system of the Danish Construction industry. The analysis shows a multifaceted landscape of innovation around an existing regime, built around existing ways of working...... and developed over generations. The regime is challenged from various niches and the socio-technical landscape through trends as globalization. Three niches (Lean Construction, BIM and System Deliveries) are subject to a detailed analysis showing partly incompatible rationales and various degrees of innovation...... potential. The paper further discusses how existing policymaking operates in a number of tensions one being between government and governance. Based on the concepts from SNM the paper introduces an innovation map in order to support the development of meta-governance policymaking. By mapping some...

  1. Cognitive maps

    DEFF Research Database (Denmark)

    Minder, Bettina; Laursen, Linda Nhu; Lassen, Astrid Heidemann

    2014-01-01

    This paper identifies three different perspectives on the relationship between design and innovation and explains implication of these different world-views of the interrelations between innovation and design. The study is based on empirical data from a series of semi-structured expert interviews...... of the interrelation becomes increasingly important. This paper seeks to clarify this interrelation and discuss how design is used in innovation.......This paper identifies three different perspectives on the relationship between design and innovation and explains implication of these different world-views of the interrelations between innovation and design. The study is based on empirical data from a series of semi-structured expert interviews....... Conceptual clustering is used to analyse and order information according to concepts or variables from within the data. The cognitive maps identified are validated through the comments of some of the same experts. The study presents three cognitive maps and respective world-views explaining how the design...

  2. An Integrated Map of Soybean Physical Map and Genetic Map

    Institute of Scientific and Technical Information of China (English)

    QI Zhaoming; LI Hui; WU Qiong; SUN Yanan; LIU Chunyan; HU Guohua; CHEN Qingshan

    2009-01-01

    Soybean is a major crop in the world, and it is a main source of plant proteins and oil. A lot of soybean genetic maps and physical maps have been constructed, but there are no integrated map between soybean physical map and genetic map. In this study, soybean genome sequence data, released by JGI (US Department of Energy's Joint Genome Institute), had been downloaded. With the software Blast 2.2.16, a total of 161 super sequences were mapped on the soybean public genetic map to construct an integrated map. The length of these super sequences accounted for 73.08% of all the genome sequence. This integrated map could be used for gene cloning, gene mining, and comparative genome of legume.

  3. Projective mapping

    DEFF Research Database (Denmark)

    Dehlholm, Christian; Brockhoff, Per B.; Bredie, Wender Laurentius Petrus

    2012-01-01

    the applied framework, semantic restrictions, the choice of type of assessors and the validation of product separations. The applied framework concerns the response surface as presented to the assessor in different shapes, e.g. rectangular, square or round. Semantic restrictions are a part of the assessor...... instructions and influence heavily the product placements and the descriptive vocabulary (Dehlholm et.al., 2012b). The type of assessors performing the method influences results with an extra aspect in Projective Mapping compared to more analytical tests, as the given spontaneous perceptions are much dependent...... on the assessor’s way of thinking. Furthermore, a suggestion for validating product separations is proposed for the case where Multiple Factor Analysis is chosen for data analysis (Dehlholm, Brockhoff & Bredie, 2012a)....

  4. Human Mind Maps

    Science.gov (United States)

    Glass, Tom

    2016-01-01

    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  5. Maps & minds : mapping through the ages

    Science.gov (United States)

    U.S. Geological Survey

    1984-01-01

    Throughout time, maps have expressed our understanding of our world. Human affairs have been influenced strongly by the quality of maps available to us at the major turning points in our history. "Maps & Minds" traces the ebb and flow of a few central ideas in the mainstream of mapping. Our expanding knowledge of our cosmic neighborhood stems largely from a small number of simple but grand ideas, vigorously pursued.

  6. Lunar Map Catalog

    Data.gov (United States)

    National Aeronautics and Space Administration — The Lunar Map Catalog includes various maps of the moon's surface, including Apollo landing sites; earthside, farside, and polar charts; photography index maps;...

  7. Mapping with the Masses: Google Map Maker

    Science.gov (United States)

    Pfund, J.

    2008-12-01

    After some 15,000 years of map making, which saw the innovations of cardinal directions, map projections for a spherical earth, and GIS analysis, many parts of the world still appear as the "Dark Continent" on modern maps. Google Map Maker intends to shine a light on these areas by tapping into the power of the GeoWeb. Google Map Maker is a website which allows you to collaborate with others on one unified map to add, edit, locate, describe, and moderate map features, such as roads, cities, businesses, parks, schools and more, for certain regions of the world using Google Maps imagery. In this session, we will show some examples of how people are mapping with this powerful tool as well as what they are doing with the data. With Google Map Maker, you can become a citizen cartographer and join the global network of users helping to improve the quality of maps and local information in your region of interest. You are invited to map the world with us!

  8. Concept mapping in lectures.

    OpenAIRE

    Lavery, Janet; Low, Adam

    2008-01-01

    Concept maps are an aid to a deep learning strategy. Developing concept maps would help students understand the relationships between concepts both within a domain and across related domains. To encourage students to explore the use of concept maps, we have integrated concept maps into a module’s lectures. We have trialled: a concept map developed by experts and given to students; another concept map developed collaboratively by the students in an interactive lecture supported by a free-tex...

  9. Mapping the Heart

    Science.gov (United States)

    Hulse, Grace

    2012-01-01

    In this article, the author describes how her fourth graders made ceramic heart maps. The impetus for this project came from reading "My Map Book" by Sara Fanelli. This book is a collection of quirky, hand-drawn and collaged maps that diagram a child's world. There are maps of her stomach, her day, her family, and her heart, among others. The…

  10. USGS Map Indices Overlay Map Service from The National Map

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The USGS Map Indices service from The National Map (TNM) consists of 1x1 Degree, 30x60 Minute (100K), 15 Minute (63K), 7.5 Minute (24K), and 3.75 Minute grid...

  11. Conserved features of cancer cells define their sensitivity of HAMLET-induced death; c-Myc and glycolysis

    OpenAIRE

    Storm, Petter; Puthia, Manoj Kumar; Aits, Sonja; Urbano, Alexander; Northen, Trent; Powers, Scott; Bowen, Ben; Chao, Yinxia; Reindl, Wolfgang; Lee, Do Yup; Sullivan, Nancy Liu; Zhang, Jianping; Trulsson, Maria; Yang, Henry; Watson, James

    2011-01-01

    HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small hairpin RNA inhibition, proteomic ...

  12. C-MYC amplification and expression in stomach cancer samples in Iranian population using two techniques of CISH and IHC

    Directory of Open Access Journals (Sweden)

    Malihea Khaleghian

    2015-07-01

    Results: Our data revealed that both diffuse and intestinal types of gastric cancer occurred significantly in men more than women. Our results showed an indication of some correlation between grades and CISH results, although the difference was not significant. Our data also showed that CISH+ patients (43.1% were more frequent in comparison with IHC+ patients (14.7%. There was a correlation between CISH and IHC. This result revealed that there was a significant difference between grades and IHC. There was also no statistically significant difference between CISH amplification in diffuse and intestinal types. Conclusion: Our conclusion is that for the treatment, management of stomach cancer, and monitoring of progress and prognosis of the tumor that is almost important for patients and clinicians, CISH test is a better and feasible to IHC test, with regards to sensitivity and specificity.

  13. Mutations in NEK8 link multiple organ dysplasia with altered Hippo signalling and increased c-MYC expression

    NARCIS (Netherlands)

    Frank, Valeska; Habbig, Sandra; Bartram, Malte P.; Eisenberger, Tobias; Veenstra-Knol, Hermine E.; Decker, Christian; Boorsma, Reinder A. C.; Goebel, Heike; Nuernberg, Gudrun; Griessmann, Anabel; Franke, Mareike; Borgal, Lori; Kohli, Priyanka; Voelker, Linus A.; Doetsch, Joerg; Nuernberg, Peter; Benzing, Thomas; Bolz, Hanno J.; Johnson, Colin; Gerkes, Erica H.; Schermer, Bernhard; Bergmann, Carsten

    2013-01-01

    Mutations affecting the integrity and function of cilia have been identified in various genes over the last decade accounting for a group of diseases called ciliopathies. Ciliopathies display a broad spectrum of phenotypes ranging from mild manifestations to lethal combinations of multiple severe sy

  14. Amino-terminal domains of c-myc and N-myc proteins mediate binding to the retinoblastoma gene product

    NARCIS (Netherlands)

    Rustgi, A.K.; Dyson, N.; Bernards, R.A.

    1991-01-01

    The proteins encoded by the myc gene family are involved is the control of cell proliferation and differentiation, and aberrant expression of myc proteins has been implicated in the genesis of a variety of neoplasms. In the carboxyl terminus, myc proteins have two domains that encode a basic domain/

  15. Tumor Suppressor DYRK1A Effects on Proliferation and Chemoresistance of AML Cells by Downregulating c-Myc

    OpenAIRE

    Qiang Liu; Na Liu; Shaolei Zang; Heng Liu; Pin Wang; Chunyan Ji; Xiulian Sun

    2014-01-01

    Acute myeloid leukemia (AML), caused by abnormal proliferation and accumulation of hematopoietic progenitor cells, is one of the most common malignancies in adults. We reported here DYRK1A expression level was reduced in the bone marrow of adult AML patients, comparing to normal controls. Overexpression of DYRK1A inhibited the proliferation of AML cell lines by increasing the proportion of cells undergoing G0/G1 phase. We reasoned that the proliferative inhibition was due to downregulation of...

  16. -Deformed nonlinear maps

    Indian Academy of Sciences (India)

    Ramaswamy Jaganathan; Sudeshna Sinha

    2005-03-01

    Motivated by studies on -deformed physical systems related to quantum group structures, and by the elements of Tsallis statistical mechanics, the concept of -deformed nonlinear maps is introduced. As a specific example, a -deformation procedure is applied to the logistic map. Compared to the canonical logistic map, the resulting family of -logistic maps is shown to have a wider spectrum of interesting behaviours, including the co-existence of attractors – a phenomenon rare in one-dimensional maps.

  17. VEGETATION MAPPING IN WETLANDS

    Directory of Open Access Journals (Sweden)

    F. PEDROTTI

    2004-01-01

    Full Text Available The current work examines the main aspects of wetland vegetation mapping, which can be summarized as analysis of the ecological-vegetational (ecotone gradients; vegetation complexes; relationships between vegetation distribution and geomorphology; vegetation of the hydrographic basin lo which the wetland in question belongs; vegetation monitoring with help of four vegetation maps: phytosociological map of the real and potential vegetation, map of vegetation dynamical tendencies, map of vegetation series.

  18. Map Projection Transitions

    OpenAIRE

    Nedjeljko Frančula; Miljenko Lapaine

    2013-01-01

    Map Projection Transitions is a very successful web application about map projections. The web page (http://www.jasondavies.com/maps/transition) pre­sents a world map with graticule and country borders in the oblique Aitoff projection, with the South Pole. The map is not static, but animated. The South Pole moves toward the bottom and Earth rotates around its poles. The animation lasts five seconds, after which the projection changes and movement continues for five seconds, after which the pr...

  19. Google Maps: You Are Here

    Science.gov (United States)

    Jacobsen, Mikael

    2008-01-01

    Librarians use online mapping services such as Google Maps, MapQuest, Yahoo Maps, and others to check traffic conditions, find local businesses, and provide directions. However, few libraries are using one of Google Maps most outstanding applications, My Maps, for the creation of enhanced and interactive multimedia maps. My Maps is a simple and…

  20. Web Mapping Using Logo on Map

    OpenAIRE

    Ximing Hou; Hao Shi

    2013-01-01

    The newly proposed Logo on Map (LoM) system consists of three modules: picture extraction module (PEM), logo matching module (LMM) and web mapping module (WMM). Since the first two modules were covered in our previous paper, the third module WMM is described here to present a complete LoM system. Current research is focused on geo-location distribution of brands on Google Maps. Pictures taken by ordinary people are extracted using Picture Extraction Module (PEM). The pictures cont...

  1. Web Mapping Using Logo on Map

    Directory of Open Access Journals (Sweden)

    Ximing Hou

    2013-01-01

    Full Text Available The newly proposed Logo on Map (LoM system consists of three modules: picture extraction module(PEM, logo matching module (LMM and web mapping module (WMM. Since the first two modules werecovered in our previous paper, the third module WMM is described here to present a complete LoM system.Current research is focused on geo-location distribution of brands on Google Maps. Pictures taken byordinary people are extracted using Picture Extraction Module (PEM. The pictures containing relevantlogos are obtained via Logo Matching Module (LMM. Brand distributions are overlaid on Google Maps.In this paper, GPS and brands are briefly described, and the implementation of Web Mapping Module(WMM based on Google Maps API is detailed. Then several experiments are carried out on the selectedtop brands. Finally the LMM-pictures are mapped on the Google Maps and the geographical distributionsof the brands are visualised. Brand uniqueness is discussed and conclusion is drawn that with uniquebrand names web mapping can visually reflect the real economic activities of a company in the world.

  2. Web Mapping Using Logo on Map

    Directory of Open Access Journals (Sweden)

    Ximing Hou

    2012-12-01

    Full Text Available The newly proposed Logo on Map (LoM system consists of three modules: picture extraction module (PEM, logo matching module (LMM and web mapping module (WMM. Since the first two modules were covered in our previous paper, the third module WMM is described here to present a complete LoM system. Current research is focused on geo-location distribution of brands on Google Maps. Pictures taken by ordinary people are extracted using Picture Extraction Module (PEM. The pictures containing relevant logos are obtained via Logo Matching Module (LMM. Brand distributions are overlaid on Google Maps. In this paper, GPS and brands are briefly described, and the implementation of Web Mapping Module (WMM based on Google Maps API is detailed. Then several experiments are carried out on the selected top brands. Finally the LMM-pictures are mapped on the Google Maps and the geographical distributions of the brands are visualised. Brand uniqueness is discussed and conclusion is drawn that with unique brand names web mapping can visually reflect the real economic activities of a company in the world.

  3. Multivalued Mappings and Applications

    Directory of Open Access Journals (Sweden)

    Jingling Zhang

    2012-01-01

    nonexpansive multi-valued mapping and to prove the strong convergence theorems of fixed point for weak relatively nonexpansive multivalued mappings in Banach spaces. The weak relatively nonexpansive multivalued mappings are more generalized than relatively nonexpansive multivalued mappings. In this paper, an example will be given which is a weak relatively nonexpansive multivalued mapping but not a relatively nonexpansive multivalued mapping. In order to get the strong convergence theorems for weak relatively nonexpansive multivalued mappings, a new monotone hybrid iteration algorithm with generalized (metric projection is presented and is used to approximate the fixed point of weak relatively nonexpansive multivalued mappings. In this paper, the notion of multivalued resolvent of maximal monotone operator has been also presented which is a weak relatively nonexpansive multivalued mapping and can be used to find the zero point of maximal monotone operator.

  4. Mapping Mutations on Phylogenies

    DEFF Research Database (Denmark)

    Nielsen, Rasmus

    2005-01-01

    This chapter provides a short review of recent methodologies developed for mapping mutations on phylogenies. Mapping of mutations, or character changes in general, using the maximum parsimony principle has been one of the most powerful tools in phylogenetics, and it has been used in a variety of ...... uncertainty in the mapping. Recently developed probabilistic methods can incorporate statistical uncertainty in the character mappings. In these methods, focus is on a probability distribution of mutational mappings instead of a single estimate of the mutational mapping....

  5. Mapping with Drupal

    CERN Document Server

    Palazzolo, Alan

    2011-01-01

    Build beautiful interactive maps on your Drupal website, and tell engaging visual stories with your data. This concise guide shows you how to create custom geographical maps from top to bottom, using Drupal 7 tools and out-of-the-box modules. You'll learn how mapping works in Drupal, with examples on how to use intuitive interfaces to map local events, businesses, groups, and other custom data. Although building maps with Drupal can be tricky, this book helps you navigate the system's complexities for creating sophisticated maps that match your site design. Get the knowledge and tools you ne

  6. Some Semi - Equivelar Maps

    CERN Document Server

    Upadhyay, Ashish K; Maity, Dipendu

    2011-01-01

    Semi-Equivelar maps are generalizations of Archimedean Solids (as are equivelar maps of the Platonic solids) to the surfaces other than $2-$Sphere. We classify some semi equivelar maps on surface of Euler characteristic -1 and show that none of these are vertex transitive. We establish existence of 12-covered triangulations for this surface. We further construct double cover of these maps to show existence of semi-equivelar maps on the surface of double torus. We also construct several semi-equivelar maps on the surfaces of Euler characteristics -8 and -10 and on non-orientable surface of Euler characteristics -2.

  7. Mapping in the cloud

    CERN Document Server

    Peterson, Michael P

    2014-01-01

    This engaging text provides a solid introduction to mapmaking in the era of cloud computing. It takes students through both the concepts and technology of modern cartography, geographic information systems (GIS), and Web-based mapping. Conceptual chapters delve into the meaning of maps and how they are developed, covering such topics as map layers, GIS tools, mobile mapping, and map animation. Methods chapters take a learn-by-doing approach to help students master application programming interfaces and build other technical skills for creating maps and making them available on the Internet. Th

  8. Active Fire Mapping Program

    Science.gov (United States)

    Active Fire Mapping Program Current Large Incidents (Home) New Large Incidents Fire Detection Maps MODIS Satellite Imagery VIIRS Satellite Imagery Fire Detection GIS Data Fire Data in Google Earth ...

  9. NAIP Status Maps Gallery

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — NAIP Status Maps Gallery. These maps illustrate what aerial imagery collection is planned, whats been collected, when it is available and how it is available. These...

  10. MapBook

    Data.gov (United States)

    National Aeronautics and Space Administration — Beginning with the systematic mapping of the lunar surface more than three decades ago, this database contains over 1600 maps of the planets and satellites of the...

  11. Recovery Action Mapping Tool

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Recovery Action Mapping Tool is a web map that allows users to visually interact with and query actions that were developed to recover species listed under the...

  12. Invariants for Parallel Mapping

    Institute of Scientific and Technical Information of China (English)

    YIN Yajun; WU Jiye; FAN Qinshan; HUANG Kezhi

    2009-01-01

    This paper analyzes the geometric quantities that remain unchanged during parallel mapping (i.e., mapping from a reference curved surface to a parallel surface with identical normal direction). The second gradient operator, the second class of integral theorems, the Gauss-curvature-based integral theorems, and the core property of parallel mapping are used to derive a series of parallel mapping invadants or geometri-cally conserved quantities. These include not only local mapping invadants but also global mapping invari-ants found to exist both in a curved surface and along curves on the curved surface. The parallel mapping invadants are used to identify important transformations between the reference surface and parallel surfaces. These mapping invadants and transformations have potential applications in geometry, physics, biome-chanics, and mechanics in which various dynamic processes occur along or between parallel surfaces.

  13. Mapping Medicare Disparities Tool

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CMS Office of Minority Health has designed an interactive map, the Mapping Medicare Disparities Tool, to identify areas of disparities between subgroups of...

  14. Letter of Map Revision

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The National Flood Hazard Layer (NFHL) data incorporates all Digital Flood Insurance Rate Map(DFIRM) databases published by FEMA, and any Letters Of Map Revision...

  15. NGS Survey Control Map

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NGS Survey Control Map provides a map of the US which allows you to find and display geodetic survey control points stored in the database of the National...

  16. Branched polynomial covering maps

    DEFF Research Database (Denmark)

    Hansen, Vagn Lundsgaard

    2002-01-01

    A Weierstrass polynomial with multiple roots in certain points leads to a branched covering map. With this as the guiding example, we formally define and study the notion of a branched polynomial covering map. We shall prove that many finite covering maps are polynomial outside a discrete branch...... set. Particular studies are made of branched polynomial covering maps arising from Riemann surfaces and from knots in the 3-sphere. (C) 2001 Elsevier Science B.V. All rights reserved....

  17. Diffusion Based Photon Mapping

    DEFF Research Database (Denmark)

    Schjøth, Lars; Fogh Olsen, Ole; Sporring, Jon

    2007-01-01

    . To address this problem we introduce a novel photon mapping algorithm based on nonlinear anisotropic diffusion. Our algorithm adapts according to the structure of the photon map such that smoothing occurs along edges and structures and not across. In this way we preserve the important illumination features......, while eliminating noise. We call our method diffusion based photon mapping....

  18. Reading Angles in Maps

    Science.gov (United States)

    Izard, Véronique; O'Donnell, Evan; Spelke, Elizabeth S.

    2014-01-01

    Preschool children can navigate by simple geometric maps of the environment, but the nature of the geometric relations they use in map reading remains unclear. Here, children were tested specifically on their sensitivity to angle. Forty-eight children (age 47:15-53:30 months) were presented with fragments of geometric maps, in which angle sections…

  19. OpenStreetMap, the Wikipedia Map

    Directory of Open Access Journals (Sweden)

    Gunther Maier

    2014-12-01

    Full Text Available This paper presents OpenStreetMap and closely related software as a resource for spatial economic research. The paper demonstrates how information can be extracted from OpenStreetMap, how it can be used as a geographical interface in web-based communication, and illustrates the value of the tools by use of a specific application, the WU campus GIS.

  20. Cosmopolitan linkage disequilibrium maps

    Directory of Open Access Journals (Sweden)

    Gibson Jane

    2005-03-01

    Full Text Available Abstract Linkage maps have been invaluable for the positional cloning of many genes involved in severe human diseases. Standard genetic linkage maps have been constructed for this purpose from the Centre d'Etude du Polymorphisme Humain and other panels, and have been widely used. Now that attention has shifted towards identifying genes predisposing to common disorders using linkage disequilibrium (LD and maps of single nucleotide polymorphisms (SNPs, it is of interest to consider a standard LD map which is somewhat analogous to the corresponding map for linkage. We have constructed and evaluated a cosmopolitan LD map by combining samples from a small number of populations using published data from a 10-megabase region on chromosome 20. In support of a pilot study, which examined a number of small genomic regions with a lower density of markers, we have found that a cosmopolitan map, which serves all populations when appropriately scaled, recovers 91 to 95 per cent of the information within population-specific maps. Recombination hot spots appear to have a dominant role in shaping patterns of LD. The success of the cosmopolitan map might be attributed to the co-localisation of hot spots in all populations. Although there must be finer scale differences between populations due to other processes (mutation, drift, selection, the results suggest that a whole-genome standard LD map would indeed be a useful resource for disease gene mapping.

  1. $2^n-$rational maps

    OpenAIRE

    Kassotakis, Pavlos; Nieszporski, Maciej; Damianou, Pantelis

    2015-01-01

    We present a natural extension of the notion of nondegenerate rational maps (quadrirational maps) to arbitrary dimensions. We refer to these maps as $2^n-$rational maps. In this note we construct a rich family of $2^n-$rational maps. These maps by construction are involutions and highly symmetric in the sense that the maps and their companion maps have the same functional form.

  2. Map Projection Transitions

    Directory of Open Access Journals (Sweden)

    Nedjeljko Frančula

    2013-06-01

    Full Text Available Map Projection Transitions is a very successful web application about map projections. The web page (http://www.jasondavies.com/maps/transition pre­sents a world map with graticule and country borders in the oblique Aitoff projection, with the South Pole. The map is not static, but animated. The South Pole moves toward the bottom and Earth rotates around its poles. The animation lasts five seconds, after which the projection changes and movement continues for five seconds, after which the projection changes again. Names of projections appear in a separate window. There are a total of 56 projections. The South Pole eventually becomes invisible and the North Pole appears at the top. Various parts of Earth appear in the center of the map by rotating around the poles.

  3. Open Land Use Map

    Directory of Open Access Journals (Sweden)

    T. Mildorf

    2014-12-01

    Full Text Available Open Land Use Map is an initiative that has been started by the Plan4business project and that will be extended as part of the SDI4Apps project in the future. This service aims to create an improved worldwide land use map. The initial map will be prepared using the CORINE Land Cover, Global Cover dataset and Open Street Map. Contributors, mainly volunteers, will able to change the geometry and assign up-to-date land use according to the HILUCS specification. For certain regions more detailed datasets, if available, will be used as an update of the Open Land Use Map. The product is treated as Open Data and users will be able to download the data in a specified format and for a selected area. The paper introduces the technical and business aspects of Open Land Use Map app including the integration and harmonisation tools, sustainability plan and apps that accompany the entire platform.

  4. Heat Capacity Mapping Mission

    Science.gov (United States)

    Nilsson, C. S.; Andrews, J. C.; Scully-Power, P.; Ball, S.; Speechley, G.; Latham, A. R. (Principal Investigator)

    1980-01-01

    The Tasman Front was delineated by airborne expendable bathythermograph survey; and an Heat Capacity Mapping Mission (HCMM) IR image on the same day shows the same principal features as determined from ground-truth. It is clear that digital enhancement of HCMM images is necessary to map ocean surface temperatures and when done, the Tasman Front and other oceanographic features can be mapped by this method, even through considerable scattered cloud cover.

  5. Mind mapping management

    OpenAIRE

    Pugalendhi, Subburethina Bharathi; Nakkeeran, Senthil kumar

    2011-01-01

    A mind map is a diagram used to represent words, ideas, tasks, or other items linked to and arranged around a central key word or idea. Mind maps are used to generate, visualize, structure, and classify ideas, and as an aid to studying and organizing information, solving problems, making decisions, and writing. The fundamentals of mind map are arranged naturally according to the importance of the concepts, and are classified into groupings, branches, or areas, with the goal of representing se...

  6. Diametrically Contractive Multivalued Mappings

    Directory of Open Access Journals (Sweden)

    S. Dhompongsa

    2007-06-01

    Full Text Available Diametrically contractive mappings on a complete metric space are introduced by V. I. Istratescu. We extend and generalize this idea to multivalued mappings. An easy example shows that our fixed point theorem is more applicable than a former one obtained by H. K. Xu. A convergence theorem of Picard iteratives is also provided for multivalued mappings on hyperconvex spaces, thereby extending a Proinov's result.

  7. Classification of Lipschitz mappings

    CERN Document Server

    Piasecki, Lukasz

    2013-01-01

    The Lipschitz Condition Nonlinear spectral radius Uniformly lipschitzian mappings Basic Facts on Banach Spaces Convexity The operator norm Dual spaces, reexivity, the weak, and weak* topologiesMean Lipschitz Condition Nonexpansive and mean nonexpansive mappings in Banach spaces General case On the Lipschitz Constants for Iterates of Mean Lipschitzian Mappings A bound for Lipschitz constants of iterates A bound for the constant k∞(T)Moving averages in Bana

  8. Multi-moment maps

    DEFF Research Database (Denmark)

    Swann, Andrew Francis; Madsen, Thomas Bruun

    2012-01-01

    We introduce a notion of moment map adapted to actions of Lie groups that preserve a closed three-form. We show existence of our multi-moment maps in many circumstances, including mild topological assumptions on the underlying manifold. Such maps are also shown to exist for all groups whose secon......-torus symmetry in terms of tri-symplectic geometry of four-manifolds. (C) 2012 Elsevier Inc. All rights reserved....

  9. Similarity transformations of MAPs

    Directory of Open Access Journals (Sweden)

    Andersen Allan T.

    1999-01-01

    Full Text Available We introduce the notion of similar Markovian Arrival Processes (MAPs and show that the event stationary point processes related to two similar MAPs are stochastically equivalent. This holds true for the time stationary point processes too. We show that several well known stochastical equivalences as e.g. that between the H 2 renewal process and the Interrupted Poisson Process (IPP can be expressed by the similarity transformations of MAPs. In the appendix the valid region of similarity transformations for two-state MAPs is characterized.

  10. Obesity Prevalence Maps

    Science.gov (United States)

    ... Breastfeeding Micronutrient Malnutrition State and Local Programs Adult Obesity Prevalence Maps Recommend on Facebook Tweet Share Compartir Obesity Prevalence in 2015 Varies Across States and Territories ...

  11. Vegetation Fuel Mapping

    Directory of Open Access Journals (Sweden)

    A. V. Volokitina

    2014-12-01

    Full Text Available All vegetation sites as objects of burning are structural complexes of various fuels. Especially complex are forest biogeoceonoses. For practical use, pyrological characteristics of vegetation are reflected on plans and maps showing both general one-sided estimations with site descriptions (for example, their fire hazard and detailed multi-sided characteristics of all compounds in the vegetation fuel complexes. The latter become basic maps for obtaining various pyrological estimations and are called vegetation fuel maps. Vegetation fuel (VF mapping can be made using two methodological approaches: first, by distinguishing pyrological vegetation categories as standard complexes; second, by individually characterizing each vegetation site in terms of VF. Obviously, the standard VF characteristic of sites can be only approximate and rough, since the possible number of studied site categories is limited. For large-scale mapping, the detailed individual characteristic of vegetation sites in terms of VF is more preferable and precise but more expensive. Therefore, historically, the first approach to VF mapping got its development, i. e. distinguishing and mapping of certain vegetation categories with standard characteristics. Foreign and Russian methodical approaches to vegetation fuel (VF classification and mapping are considered. Examples of VF mapping at different scales and guidelines for their use are given.

  12. Lyman Alpha Mapping Project (LAMP) Brightness Maps

    Science.gov (United States)

    Retherford, Kurt D.; Gladstone, G.; Stern, S.; Egan, A. F.; Miles, P. F.; Parker, J. W.; Greathouse, T. K.; Davis, M. W.; Slater, D. C.; Kaufmann, D. E.; Versteeg, M. H.; Feldman, P. D.; Hurley, D. M.; Pryor, W. R.; Hendrix, A. R.

    2010-10-01

    The Lyman Alpha Mapping Project (LAMP) is an ultraviolet (UV) spectrograph on the Lunar Reconnaissance Orbiter (LRO) that is designed to map the lunar albedo at far-UV wavelengths. LAMP primarily measures interplanetary Hydrogen Lyman-alpha sky-glow and far-UV starlight reflected from the night-side lunar surface, including permanently shadowed regions (PSRs) near the poles. Dayside observations are also obtained. Brightness maps sorted by wavelength (including the Lyman-alpha wavelength of 121.6 nm) are reported for the polar regions, with a few regions of interest reported in more detail. LAMP's spectral range of 58 nm to 196 nm includes a water ice spectral feature near 160 nm, which provides a diagnostic tool for detecting water on the lunar surface that is complementary to recent discoveries using infrared and radio frequency techniques. Progress towards producing far-UV albedo maps and searching for water ice signatures will be reported. We'll discuss how LAMP data may address questions regarding how water is formed on the moon, transported through the lunar atmosphere, and deposited in the PSRs.

  13. On circle map coupled map lattice

    CERN Document Server

    Ahmed, E

    2002-01-01

    Circle map in one and two dimensions is studied. Both its stability, synchronization using bounded control and persistence is discussed. This work is expected to be applicable in ecology where spatial effects are known to be important. Also it will be relevant to systems where delay effects are not negligible.

  14. Acoustic mapping velocimetry

    Science.gov (United States)

    Muste, M.; Baranya, S.; Tsubaki, R.; Kim, D.; Ho, H.; Tsai, H.; Law, D.

    2016-05-01

    Knowledge of sediment dynamics in rivers is of great importance for various practical purposes. Despite its high relevance in riverine environment processes, the monitoring of sediment rates remains a major and challenging task for both suspended and bed load estimation. While the measurement of suspended load is currently an active area of testing with nonintrusive technologies (optical and acoustic), bed load measurement does not mark a similar progress. This paper describes an innovative combination of measurement techniques and analysis protocols that establishes the proof-of-concept for a promising technique, labeled herein Acoustic Mapping Velocimetry (AMV). The technique estimates bed load rates in rivers developing bed forms using a nonintrusive measurements approach. The raw information for AMV is collected with acoustic multibeam technology that in turn provides maps of the bathymetry over longitudinal swaths. As long as the acoustic maps can be acquired relatively quickly and the repetition rate for the mapping is commensurate with the movement of the bed forms, successive acoustic maps capture the progression of the bed form movement. Two-dimensional velocity maps associated with the bed form migration are obtained by implementing algorithms typically used in particle image velocimetry to acoustic maps converted in gray-level images. Furthermore, use of the obtained acoustic and velocity maps in conjunction with analytical formulations (e.g., Exner equation) enables estimation of multidirectional bed load rates over the whole imaged area. This paper presents a validation study of the AMV technique using a set of laboratory experiments.

  15. Map-A-Planet

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The Map-A-Planet website allows users to create and download custom image maps of planets and satellites from a variety of missions in an easy to use web interface

  16. Multivariate Nonnegative Quadratic Mappings

    NARCIS (Netherlands)

    Luo, Z-Q; Sturm, J.F.; Zhang, S.

    2003-01-01

    In this paper we study several issues related to the characterization of speci c classes of multivariate quadratic mappings that are nonnegative over a given domain, with nonnegativity de ned by a pre-speci ed conic order.In particular, we consider the set (cone) of nonnegative quadratic mappings de

  17. Android Mapping Application

    Directory of Open Access Journals (Sweden)

    Abdalwhab Bakheet

    2014-04-01

    Full Text Available Location-aware and mapping applications have gone f rom a desirable feature to an essential part of any smart phone. Whether a user is checking into a social network, looking for a pharmacy in the middle of the night, or located in somewhere and needs help, the key is always the same: location. In this project, an Android mapping application is developed. The application is able to display the map of the whole world while online or, display a pre-downloaded map while offline, track the user’s location, display a compass to determine north, send the user’s location to others in case of emergency using SMS, receive and interpret received location from the message, display it on the map, and notify the user by the reception of the location. The application was developed using agile methodol ogy. It, met its objectives and successfully passed 91% of the final system test, recording that some limitations were discovered, the application needs further testing and can be implem ented for particular company or university using their own maps or editing the maps in OSM (op en street maps.

  18. Iconicity as structure mapping.

    Science.gov (United States)

    Emmorey, Karen

    2014-09-19

    Linguistic and psycholinguistic evidence is presented to support the use of structure-mapping theory as a framework for understanding effects of iconicity on sign language grammar and processing. The existence of structured mappings between phonological form and semantic mental representations has been shown to explain the nature of metaphor and pronominal anaphora in sign languages. With respect to processing, it is argued that psycholinguistic effects of iconicity may only be observed when the task specifically taps into such structured mappings. In addition, language acquisition effects may only be observed when the relevant cognitive abilities are in place (e.g. the ability to make structural comparisons) and when the relevant conceptual knowledge has been acquired (i.e. information key to processing the iconic mapping). Finally, it is suggested that iconicity is better understood as a structured mapping between two mental representations than as a link between linguistic form and human experience.

  19. Geologic map of Mars

    Science.gov (United States)

    Tanaka, Kenneth L.; Skinner, James A.; Dohm, James M.; Irwin, Rossman P.; Kolb, Eric J.; Fortezzo, Corey M.; Platz, Thomas; Michael, Gregory G.; Hare, Trent M.

    2014-01-01

    This global geologic map of Mars, which records the distribution of geologic units and landforms on the planet's surface through time, is based on unprecedented variety, quality, and quantity of remotely sensed data acquired since the Viking Orbiters. These data have provided morphologic, topographic, spectral, thermophysical, radar sounding, and other observations for integration, analysis, and interpretation in support of geologic mapping. In particular, the precise topographic mapping now available has enabled consistent morphologic portrayal of the surface for global mapping (whereas previously used visual-range image bases were less effective, because they combined morphologic and albedo information and, locally, atmospheric haze). Also, thermal infrared image bases used for this map tended to be less affected by atmospheric haze and thus are reliable for analysis of surface morphology and texture at even higher resolution than the topographic products.

  20. Application of ecological mapping

    International Nuclear Information System (INIS)

    The US Fish and Wildlife Service has initiated the production of a comprehensive ecological inventory map series for use as a major new planning tool. Important species data along with special land use designations are displayed on 1:250,000 scale topographic base maps. Sets of maps have been published for the Atlantic and Pacific coastal areas of the United States. Preparation of a map set for the Gulf of Mexico is underway at the present time. Potential application of ecological inventory map series information to a typical land disposal facility could occur during the narrowing of the number of possible disposal sites, the design of potential disposal site studies of ecological resources, the preparation of the environmental report, and the regulatory review of license applications. 3 figures, 3 tables

  1. Mental Mapping: A Classroom Strategy

    Science.gov (United States)

    Solomon, Les

    1978-01-01

    Examines potential uses of mental maps in the classroom by reviewing research efforts, providing an example of the differences between mental maps of two student groups, and suggesting how to use mental maps in the geography curriculum. Mental mapping (or cognitive mapping) refers to individuals' processes of collecting, storing, and retrieving…

  2. nowCOAST's Map Service for Political Map Overlays

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Map Information: This nowCOAST map service provides map overlays depicting the boundaries of U.S. states, territories, counties and townships/county subdivisions,...

  3. nowCOAST's Map Service for Transportation Map Overlays

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Map Information: This nowCOAST map service provides maps depicting the locations of major world airport runways, major U.S. seaports, and latitude/longitude grid...

  4. Color on emergency mapping

    Science.gov (United States)

    Jiang, Lili; Qi, Qingwen; Zhang, An

    2007-06-01

    There are so many emergency issues in our daily life. Such as typhoons, tsunamis, earthquake, fires, floods, epidemics, etc. These emergencies made people lose their lives and their belongings. Every day, every hour, even every minute people probably face the emergency, so how to handle it and how to decrease its hurt are the matters people care most. If we can map it exactly before or after the emergencies; it will be helpful to the emergency researchers and people who live in the emergency place. So , through the emergency map, before emergency is occurring we can predict the situation, such as when and where the emergency will be happen; where people can refuge, etc. After disaster, we can also easily assess the lost, discuss the cause and make the lost less. The primary effect of mapping is offering information to the people who care about the emergency and the researcher who want to study it. Mapping allows the viewers to get a spatial sense of hazard. It can also provide the clues to study the relationship of the phenomenon in emergency. Color, as the basic element of the map, it can simplify and clarify the phenomenon. Color can also affects the general perceptibility of the map, and elicits subjective reactions to the map. It is to say, structure, readability, and the reader's psychological reactions can be affected by the use of color.

  5. Blind Friendly Maps

    OpenAIRE

    Červenka, Petr; Břinda, Karel; Seifert, Radek; Hofman, Petr

    2016-01-01

    Space concept of the surrounding area is one of the most important preconditions of the independent mobility and orientation of the blind people. Tactile maps are considered to be the most appropriate source of spatial information. One of the main problems of the tactile maps usage is their problematic accessibility for the blind users since they are not available in time and with up-to-date content. The map production is a matter of tedious manual work and a result of expensive and time-cons...

  6. Diffusion Based Photon Mapping

    DEFF Research Database (Denmark)

    Schjøth, Lars; Olsen, Ole Fogh; Sporring, Jon

    2006-01-01

    . To address this problem we introduce a novel photon mapping algorithm based on nonlinear anisotropic diffusion. Our algorithm adapts according to the structure of the photon map such that smoothing occurs along edges and structures and not across. In this way we preserve the important illumination features......Density estimation employed in multi-pass global illumination algorithms give cause to a trade-off problem between bias and noise. The problem is seen most evident as blurring of strong illumination features. In particular this blurring erodes fine structures and sharp lines prominent in caustics......, while eliminating noise. We call our method diffusion based photon mapping....

  7. Map: Geospatial paradigm

    OpenAIRE

    Ikonović Vesna

    2006-01-01

    There are different definitions of map. There is no one which is accepted in whole world or at least from the most cartographers. In the paper it will be given several definitions which are, at the best way, (according to the author’s opinion) reflecting essence of map as a model of reality. Map as a universal meaning of researching can’t serve only for representing particular geospace (spatial system) or some its element, or to give only clear view about geographical dispersion of objects, p...

  8. Map: Geospatial paradigm

    Directory of Open Access Journals (Sweden)

    Ikonović Vesna

    2006-01-01

    Full Text Available There are different definitions of map. There is no one which is accepted in whole world or at least from the most cartographers. In the paper it will be given several definitions which are, at the best way, (according to the author’s opinion reflecting essence of map as a model of reality. Map as a universal meaning of researching can’t serve only for representing particular geospace (spatial system or some its element, or to give only clear view about geographical dispersion of objects, phenomena and processes, but have to make possible studying the patterns of that dispersion, as well as their mutual connections and conditions.

  9. Northern Hemisphere Synoptic Weather Maps

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Daily Series of Synoptic Weather Maps. Part I consists of plotted and analyzed daily maps of sea-level and 500-mb maps for 0300, 0400, 1200, 1230, 1300, and 1500...

  10. Irreducibility properties of Keller maps

    OpenAIRE

    de Bondt, Michiel; Yan, Dan

    2013-01-01

    Jedrzejewicz showed that a polynomial map over a field of characteristic zero is invertible, if and only if the corresponding endomorphism maps irreducible polynomials to irreducible polynomials. Furthermore, he showed that a polynomial map over a field of characteristic zero is a Keller map, if and only if the corresponding endomorphism maps irreducible polynomials to square-free polynomials. We show that the latter endomorphism maps other square-free polynomials to square-free polynomials a...

  11. MAPPING IN MICRONESIA.

    Science.gov (United States)

    Olsen, Randle W.; Swinnerton, J.R.

    1984-01-01

    The U. S. Geological Survey has recently completed a series of new topographic maps of Micronesia in cooperation with the Trust Territory of the Pacific Islands, the Federal agency administering the islands. Monocolor 1:10,000-scale manuscripts were compiled, from which 1:25,000-scale metric quadrangles were derived with symbology consistent with USGS quadrangle mapping. The publication of these new maps coincides with the impending political changes resulting from self-determination referendums held in Micronesia. Local sources have helped considerably with field logistics and resolution of geographic name controversies. Technical aspects of this project included development of tropical feature symbology, location of cadastral subdivisions and associated boundaries and mapping of many outlying coral reefs.

  12. The CPD Maps System

    Data.gov (United States)

    Department of Housing and Urban Development — CPD Maps includes data on the locations of existing CDBG, HOME, public housing and other HUD-funded community assets, so that users can view past investments...

  13. Interest rates mapping

    CERN Document Server

    Kanevski, M; Pozdnoukhov, A; Timonin, V

    2007-01-01

    The present study deals with the analysis and mapping of Swiss franc interest rates. Interest rates depend on time and maturity, defining term structure of the interest rate curves (IRC). In the present study IRC are considered in a two-dimensional feature space - time and maturity. Geostatistical models and machine learning algorithms (multilayer perceptron and Support Vector Machines) were applied to produce interest rate maps. IR maps can be used for the visualisation and patterns perception purposes, to develop and to explore economical hypotheses, to produce dynamic asses-liability simulations and for the financial risk assessments. The feasibility of an application of interest rates mapping approach for the IRC forecasting is considered as well.

  14. MUTYH Associated Polyposis (MAP)

    DEFF Research Database (Denmark)

    Poulsen, Marie Louise Mølgaard; Bisgaard, M L

    2008-01-01

    MUTYH Associated Polyposis (MAP), a Polyposis predisposition caused by biallelic mutations in the Base Excision Repair (BER) gene MUTYH, confers a marked risk of colorectal cancer (CRC). The MAP phenotype is difficult to distinguish from other hereditary CRC syndromes. Especially from Familial...... Adenomatous Polyposis (FAP) and to a lesser extend Lynch Syndrome, which are caused by germline mutations in the APC and Mismatch Repair (MMR) genes, respectively.Here we review research findings regarding MUTYH interactions, genotypic and phenotypic characteristics of MAP, as well as surveillance...... and treatment of the disease. The applied papers, published between 1/1 2002- 1/2 2008, were found through PubMed.The exact role of MUTYH in CRC tumorgenesis is still uncertain, although MAP tumors show distinct molecular features, including somatic G:C>T:A transversions in the APC gene. Furthermore...

  15. Daily Weather Maps

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Several different government offices have published the Daily weather maps over its history. The publication has also gone by different names over time. The U.S....

  16. PDS Planetary Maps API

    Data.gov (United States)

    National Aeronautics and Space Administration — We are developing a set of NASA Extensions to the Google Maps API—and soon to other frameworks such as OpenLayers as well—that will make these platforms more useful...

  17. NOS Bathymetric Maps

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This collection of bathymetric contour maps which represent the seafloor topography includes over 400 individual titles and covers US offshore areas including...

  18. Minidoka - Invasive Species Mapping

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Locate and map, via the use of GPS, Rush skeletonweed on the refuge. Located areas then entered into GIS to allow refuge staff to pin point locations and treat this...

  19. Mapping the HISS Dipole

    International Nuclear Information System (INIS)

    The principal component of the Bevalac HISS facility is a large super-conducting 3 Tesla dipole. The facility's need for a large magnetic volume spectrometer resulted in a large gap geometry - a 2 meter pole tip diameter and a 1 meter pole gap. Obviously, the field required detailed mapping for effective use as a spectrometer. The mapping device was designed with several major features in mind. The device would measure field values on a grid which described a closed rectangular solid. The grid would be a regular with the exact measurement intervals adjustable by software. The device would function unattended over the long period of time required to complete a field map. During this time, the progress of the map could be monitored by anyone with access to the HISS VAX computer. Details of the mechanical, electrical, and control design follow

  20. TOXMAP®: Environmental Health Maps

    Data.gov (United States)

    U.S. Department of Health & Human Services — TOXMAP® is a Geographic Information System (GIS) that uses maps of the United States and Canada to help users visually explore data primarily from the EPA's Toxics...

  1. Haz-Map

    Data.gov (United States)

    U.S. Department of Health & Human Services — Haz-Map is an occupational health database designed for health and safety professionals and for consumers seeking information about the adverse effects of workplace...

  2. FLOODPLAIN MAPPING, Bandera, TEXAS

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — The Floodplain Mapping/Redelineation study deliverables depict and quantify the flood risks for the study area. The primary risk classifications used are the...

  3. MetaMap

    Data.gov (United States)

    U.S. Department of Health & Human Services — MetaMap is a highly configurable application developed by the Lister Hill National Center for Biomedical Communications at the National Library of Medicine (NLM) to...

  4. Programming with Hierarchical Maps

    DEFF Research Database (Denmark)

    Ørbæk, Peter

    This report desribes the hierarchical maps used as a central data structure in the Corundum framework. We describe its most prominent features, ague for its usefulness and briefly describe some of the software prototypes implemented using the technology....

  5. National Coastal Mapping Program

    Data.gov (United States)

    Army Corps of Engineers, Department of the Army, Department of Defense — The U. S. Army Corps of Engineers (USACE) National Coastal Mapping Program (NCMP) is designed to provide high-resolution elevation and imagery data along U.S....

  6. Marketplace Enrollment Maps

    Data.gov (United States)

    U.S. Department of Health & Human Services — The maps show the distribution of consumers in a state who enrolled in marketplace plans through federally facilitated, partnership, and supported state-based...

  7. Public Waters Inventory Maps

    Data.gov (United States)

    Minnesota Department of Natural Resources — This theme is a scanned and rectified version of the Minnesota DNR - Division of Waters "Public Waters Inventory" (PWI) maps. DNR Waters utilizes a small scale...

  8. Complete Quasiconvex Mappings in Polydisc

    Institute of Scientific and Technical Information of China (English)

    LIU Tai-shun; ZHANG Wen-jun

    2006-01-01

    In this paper,a class of biholomorphic mappings called complete quasiconvex mappings is introduced and studied in bounded convex Reinhardt domains of Cn.Through a detailed analysis of the analytic characterization for this class of mappings,it is shown that this class of mappings contains the convex mappings and is also a subset of the class of starlike mappings.In the special case of the polydisc,a decomposition theorem is established for the complete quasiconvex mappings,which in turn is used to derive an improved sufficient condition for the convex mappings.

  9. Random mapping statistics

    OpenAIRE

    Flajolet, Philippe; Odlyzko, Andrew M.

    1989-01-01

    Random mappings from a finite set into itself are either a heuristic or an exact model for a variety of applications in random number generation, computational number theory, cryptography, and the analysis of algorithms at large. This paper introduces a general framework in which the analysis of about twenty characteristic parameters of random mappings is carried out. These parameters are studied systematically through the use of generating functions and singularity analysis. In particular, a...

  10. Sri Lanka Malaria Maps

    OpenAIRE

    Hoek Wim; Gunawardena Dissanayake M; Briët Olivier JT; Amerasinghe Felix P

    2003-01-01

    Abstract Background Despite a relatively good national case reporting system in Sri Lanka, detailed maps of malaria distribution have not been publicly available. Methods In this study, monthly records over the period 1995 – 2000 of microscopically confirmed malaria parasite positive blood film readings, at sub-district spatial resolution, were used to produce maps of malaria distribution across the island. Also, annual malaria trends at district resolution were displayed for the period 1995 ...

  11. Olympic Maps Available

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Beijing is publishing a set of Olympic maps covering everything from the location of sporting venues to the city’s history As soon as Zhou Liyi hopped off the train from Shanghai to Beijing, he hurried to Wangfujing Xinhua Book Store,one of the largest of its kind in Beijing,to buy an Olympic map. Zhou is a Shanghai resident who came to Beijing on business and plans to return as a

  12. Ogallala Aquifer Mapping Program

    International Nuclear Information System (INIS)

    A computerized data file has been established which can be used efficiently by the contour-plotting program SURFACE II to produce maps of the Ogallala aquifer in 17 counties of the Texas Panhandle. The data collected have been evaluated and compiled into three sets, from which SURFACE II can generate maps of well control, aquifer thickness, saturated thickness, water level, and the difference between virgin (pre-1942) and recent (1979 to 1981) water levels. 29 figures, 1 table

  13. Irreversible quantum baker map.

    Science.gov (United States)

    Łoziński, Artur; Pakoński, Prot; Zyczkowski, Karol

    2002-12-01

    We propose a generalization of the model of classical baker map on the torus, in which the images of two parts of the phase space do overlap. This transformation is irreversible and cannot be quantized by means of a unitary Floquet operator. A corresponding quantum system is constructed as a completely positive map acting in the space of density matrices. We investigate spectral properties of this superoperator and their link with the increase of the entropy of initially pure states.

  14. Irreversible Quantum Baker Map

    CERN Document Server

    Lozinski, A; Zyczkowski, K; Lozinski, Artur; Pakonski, Prot; Zyczkowski, Karol

    2002-01-01

    We propose a generalization of the model of classical baker map on the torus, in which the images of two parts of the phase space do overlap. This transformation is irreversible and cannot be quantized by means of a unitary Floquet operator. A corresponding quantum system is constructed as a completely positive map acting in the space of density matrices. We investigate spectral properties of this super-operator and their link with the increase of the entropy of initially pure states.

  15. Maps of Computer Science

    CERN Document Server

    Fried, Daniel

    2013-01-01

    We describe a practical approach for visual exploration of research papers. Specifically, we use the titles of papers from the DBLP database to create what we call maps of computer science (MoCS). Words and phrases from the paper titles are the cities in the map, and countries are created based on word and phrase similarity, calculated using co-occurrence. With the help of heatmaps, we can visualize the profile of a particular conference or journal over the base map. Similarly, heatmap profiles can be made of individual researchers or groups such as a department. The visualization system also makes it possible to change the data used to generate the base map. For example, a specific journal or conference can be used to generate the base map and then the heatmap overlays can be used to show the evolution of research topics in the field over the years. As before, individual researchers or research groups profiles can be visualized using heatmap overlays but this time over the journal or conference base map. Fin...

  16. Interactive Metro Map Editing.

    Science.gov (United States)

    Wang, Yu-Shuen; Peng, Wan-Yu

    2016-02-01

    Manual editing of a metro map is essential because many aesthetic and readability demands in map generation cannot be achieved by using a fully automatic method. In addition, a metro map should be updated when new metro lines are developed in a city. Considering that manually designing a metro map is time-consuming and requires expert skills, we present an interactive editing system that considers human knowledge and adjusts the layout to make it consistent with user expectations. In other words, only a few stations are controlled and the remaining stations are relocated by our system. Our system supports both curvilinear and octilinear layouts when creating metro maps. It solves an optimization problem, in which even spaces, route straightness, and maximum included angles at junctions are considered to obtain a curvilinear result. The system then rotates each edge to extend either vertically, horizontally, or diagonally while approximating the station positions provided by users to generate an octilinear layout. Experimental results, quantitative and qualitative evaluations, and user studies show that our editing system is easy to use and allows even non-professionals to design a metro map.

  17. MAPS of Cancer

    Science.gov (United States)

    Gray, Lincoln

    1998-01-01

    Our goal was to produce an interactive visualization from a mathematical model that successfully predicts metastases from head and neck cancer. We met this goal early in the project. The visualization is available for the public to view. Our work appears to fill a need for more information about this deadly disease. The idea of this project was to make an easily interpretable visualization based on what we call "functional maps" of disease. A functional map is a graphic summary of medical data, where distances between parts of the body are determined by the probability of disease, not by anatomical distances. Functional maps often beat little resemblance to anatomical maps, but they can be used to predict the spread of disease. The idea of modeling the spread of disease in an abstract multidimensional space is difficult for many people. Our goal was to make the important predictions easy to see. NASA must face this problem frequently: how to help laypersons and professionals see important trends in abstract, complex data. We took advantage of concepts perfected in NASA's graphics libraries. As an analogy, consider a functional map of early America. Suppose we choose travel times, rather than miles, as our measures of inter-city distances. For Abraham Lincoln, travel times would have been the more meaningful measure of separation between cities. In such a map New Orleans would be close to Memphis because of the Mississippi River. St. Louis would be close to Portland because of the Oregon Trail. Oklahoma City would be far from Little Rock because of the Cheyenne. Such a map would look puzzling to those of us who have always seen physical maps, but the functional map would be more useful in predicting the probabilities of inter-site transit. Continuing the analogy, we could predict the spread of social diseases such as gambling along the rivers and cattle rustling along the trails. We could simply print the functional map of America, but it would be more interesting

  18. Development of base maps' role in soil mapping

    Science.gov (United States)

    Miller, Brad; Brevik, Eric

    2014-05-01

    One of the ultimate goals of soil science is the production of accurate soil maps, but historically these thematic maps have relied upon base maps for positional reference and later for parameters that help predict soil properties. This presentation reviews the history of base maps and the dependence of soil mapping on them. The availability of geographic technology for producing these base maps has constrained and directed the geographic study of soil. A lack of accurate methods for determining location limited early geographic description of soils to narratives. The availability of accurate topographic maps in the late 18th century, fueled by governments' interests in documenting national boundaries and popular interest in world atlases, provided the first base maps for soil geographers. These soil maps primarily used the topographic maps as a spatial reference onto which the thematic details were drawn. Due to the late start of a systematic topographic survey in the United States, early Soil Survey maps depended upon plat maps for spatial reference. The adoption of aerial photographs in the process of soil mapping increased the role of base maps as predictive parameters. In the current geospatial revolution, global positioning systems and geographic information systems have nearly replaced the need for base maps to provide spatial reference. Today, base maps are more likely to be used as parameters in landscape models for predicting the spatial distribution of soil properties and classes. As model parameters for digital soil maps, base maps constitute the library of predictive variables and constrain the supported resolution of the soil map. This change in the relationship between base maps and the soil map is a paradigm shift that affects fundamental definitions of geography, such as scale, resolution, and detectable features. These concepts are the essential tools used to study the spatial characteristics of Earth Systems.

  19. Geologic mapping of Vesta

    Science.gov (United States)

    Yingst, R. A.; Mest, S. C.; Berman, D. C.; Garry, W. B.; Williams, D. A.; Buczkowski, D.; Jaumann, R.; Pieters, C. M.; De Sanctis, M. C.; Frigeri, A.; Le Corre, L.; Preusker, F.; Raymond, C. A.; Reddy, V.; Russell, C. T.; Roatsch, T.; Schenk, P. M.

    2014-11-01

    We report on a preliminary global geologic map of Vesta, based on data from the Dawn spacecraft's High-Altitude Mapping Orbit (HAMO) and informed by Low-Altitude Mapping Orbit (LAMO) data. This map is part of an iterative mapping effort; the geologic map has been refined with each improvement in resolution. Vesta has a heavily-cratered surface, with large craters evident in numerous locations. The south pole is dominated by an impact structure identified before Dawn's arrival. Two large impact structures have been resolved: the younger, larger Rheasilvia structure, and the older, more degraded Veneneia structure. The surface is also characterized by a system of deep, globe-girdling equatorial troughs and ridges, as well as an older system of troughs and ridges to the north. Troughs and ridges are also evident cutting across, and spiraling arcuately from, the Rheasilvia central mound. However, no volcanic features have been unequivocally identified. Vesta can be divided very broadly into three terrains: heavily-cratered terrain; ridge-and-trough terrain (equatorial and northern); and terrain associated with the Rheasilvia crater. Localized features include bright and dark material and ejecta (some defined specifically by color); lobate deposits; and mass-wasting materials. No obvious volcanic features are evident. Stratigraphy of Vesta's geologic units suggests a history in which formation of a primary crust was followed by the formation of impact craters, including Veneneia and the associated Saturnalia Fossae unit. Formation of Rheasilvia followed, along with associated structural deformation that shaped the Divalia Fossae ridge-and-trough unit at the equator. Subsequent impacts and mass wasting events subdued impact craters, rims and portions of ridge-and-trough sets, and formed slumps and landslides, especially within crater floors and along crater rims and scarps. Subsequent to the formation of Rheasilvia, discontinuous low-albedo deposits formed or were

  20. Conformal mappings and CR mappings on the Engel group

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    We show that conformal mappings between the Engel groups are CR or anti-CR mappings. This reduces the determination of conformal mappings to a problem in the theory of several complex analysis.The result about the group of CR automorphisms is used to determine the identity component of the group of conformal mappings on the Engel group.

  1. Insurance flood maps

    International Nuclear Information System (INIS)

    Dear Client, in half an hour you will be hit by a flood, please get ready. Your insurance company. Such a phone call or SMS could only mean two things: drunk friends or an insurance company using a flood map. In the second case, the best thing to do on receiving such a message is to act quickly. The advantage of flood maps do not necessarily have to start at the moment a flood becomes an immediate threat. The primary role of flood maps is to allow for a fairer calculation of insurance rates. Insurance companies can save on re-insurance costs as if the risk level is predictable re-insurance companies may offer better rates. The three largest insurance companies: Allianz - Slovenska poistovna, Kooperativa and Ceska poistovna Slovensko have begun introducing flood maps. These three companies control about 75% of the market. And if competition does not force other market participants to adopt the same approach, re-insurance companies certainly will. They will charge more for a less specifically defined risk level. So far insurance companies have not encountered this pressure, re-insurance companies are helping them set up the flood maps and in the coming years flood maps will become a common tool. Then the pressure will be there: if a insurance company uses a different calculation method, the final price may differ greatly from the competition's. If the price is higher, the company will lose clients and if the price is much lower, the risk has probably not been calculated correctly and the insurance company may suffer substantial losses in the event of a major flood. In short, the investment of several million Sk in a flood map is essential

  2. Introduction to "Mapping Vietnameseness"

    Directory of Open Access Journals (Sweden)

    Hue-Tam Ho Tai

    2016-09-01

    Full Text Available Vietnam and China are currently engaged in a map war, with each country using ancient maps to buttress its claims to territorial sovereignty over some uninhabited islands in the South China Sea (in Chinese terminology, also known as the Eastern Sea (in Vietnamese. But what do maps in fact represent? What is meant by “territory”? How are territorial limits conceived? These questions were raised in a May 2015 workshop inspired by Thongchai Winichakul’s Siam Mapped: A History of the Geo-Body of a Nation (1994, a groundbreaking book that traces the transformation of Thai geographical consciousness as a result of Siam’s encounter with Western powers in the nineteenth century. While many of Thongchai’s insights apply to the Vietnamese case, as the first of the three articles included in this special issue of Cross-Currents shows, some of the 2015 workshop participants’ conclusions departed from his, especially regarding the formation of a Vietnamese geographical consciousness before the colonial period.[i] This is true of the other two papers, which focus specifically on the construction of borders and the associated production of maps in the nineteenth century before French colonial conquest... Notes 1 Thanks are due to the Max Planck Institute for the Study of Religious and Ethnic Change in Gottingen, Germany, for its gracious hosting and generous funding of the conference, together with the Asia Center of Harvard University.

  3. Web Interactive Campus Map

    Directory of Open Access Journals (Sweden)

    Marylene S. Eder

    2015-03-01

    Full Text Available Abstract Interactive campus map is a web based application that can be accessed through a web browser. With the Google Map Application Programming Interface availability of the overlay function has been taken advantage to create custom map functionalities. Collection of building points were gathered for routing and to create polygons which serves as a representation of each building. The previous campus map provides a static visual representation of the campus. It uses legends building name and its corresponding building number in providing information. Due to its limited capabilities it became a realization to the researchers to create an interactive campus map.Storing data about the building room and staff information and university events and campus guide are among the primary features that this study has to offer. Interactive Web-based Campus Information System is intended in providing a Campus Information System.It is open to constant updates user-friendly for both trained and untrained users and capable of responding to all needs of users and carrying out analyses. Based on the data gathered through questionnaires researchers analyzed the results of the test survey and proved that the system is user friendly deliver information to users and the important features that the students expect.

  4. Sri Lanka Malaria Maps

    Directory of Open Access Journals (Sweden)

    van der Hoek Wim

    2003-07-01

    Full Text Available Abstract Background Despite a relatively good national case reporting system in Sri Lanka, detailed maps of malaria distribution have not been publicly available. Methods In this study, monthly records over the period 1995 – 2000 of microscopically confirmed malaria parasite positive blood film readings, at sub-district spatial resolution, were used to produce maps of malaria distribution across the island. Also, annual malaria trends at district resolution were displayed for the period 1995 – 2002. Results The maps show that Plasmodium vivax malaria incidence has a marked variation in distribution over the island. The incidence of Plasmodium falciparum malaria follows a similar spatial pattern but is generally much lower than that of P. vivax. In the north, malaria shows one seasonal peak in the beginning of the year, whereas towards the south a second peak around June is more pronounced. Conclusion This paper provides the first publicly available maps of both P. vivax and P. falciparum malaria incidence distribution on the island of Sri Lanka at sub-district resolution, which may be useful to health professionals, travellers and travel medicine professionals in their assessment of malaria risk in Sri Lanka. As incidence of malaria changes over time, regular updates of these maps are necessary.

  5. Mapping sequences by parts

    Directory of Open Access Journals (Sweden)

    Guziolowski Carito

    2007-09-01

    Full Text Available Abstract Background: We present the N-map method, a pairwise and asymmetrical approach which allows us to compare sequences by taking into account evolutionary events that produce shuffled, reversed or repeated elements. Basically, the optimal N-map of a sequence s over a sequence t is the best way of partitioning the first sequence into N parts and placing them, possibly complementary reversed, over the second sequence in order to maximize the sum of their gapless alignment scores. Results: We introduce an algorithm computing an optimal N-map with time complexity O (|s| × |t| × N using O (|s| × |t| × N memory space. Among all the numbers of parts taken in a reasonable range, we select the value N for which the optimal N-map has the most significant score. To evaluate this significance, we study the empirical distributions of the scores of optimal N-maps and show that they can be approximated by normal distributions with a reasonable accuracy. We test the functionality of the approach over random sequences on which we apply artificial evolutionary events. Practical Application: The method is illustrated with four case studies of pairs of sequences involving non-standard evolutionary events.

  6. Maps, immersions and permutations

    CERN Document Server

    Coquereaux, Robert

    2015-01-01

    We consider the problem of counting and of listing topologically inequivalent "planar" {4-valent} maps with a single component and a given number n of vertices. This enables us to count and to tabulate immersions of a circle in a sphere (spherical curves), extending results by Arnold and followers. Different options where the circle and/or the sphere are/is oriented are considered in turn, following Arnold's classification of the different types of symmetries. We also consider the case of bicolourable and bicoloured maps or immersions, where faces are bicoloured. Our method extends to immersions of a circle in a higher genus Riemann surface. There the bicolourability is no longer automatic and has to be assumed. We thus have two separate countings in non zero genus, that of bicolourable maps and that of general maps. We use a classical method of encoding maps in terms of permutations, on which the constraints of "one-componentness" and of a given genus may be applied. Depending on the orientation issue and on...

  7. Using KML for Thematic Mapping

    Science.gov (United States)

    Sandvik, B.

    2008-12-01

    Thematic mapping has a long history in cartography, but the new geobrowsers tend not to focus on this aspect of geographical information representation. This talk demonstrates how Keyhole Markup Language (KML) and geobrowsers can be used for thematic mapping. Due to their huge public interest and relative accessibility, geobrowsers are potentially capable of bringing thematic maps or visualisations to a wider audience. KML is not targeted towards thematic mapping, but it is possible to use KML elements in ways that were probably not intended. Current possibilities for making proportional symbol maps, chart maps, choropleth maps and animated maps with KML will be presented. An open source Thematic Mapping Engine (TME) has been developed as a proof-of-concept. This application allows the user to make thematic maps through an easy-to-use web interface. TME provides a low-cost solution suitable for non-profits and public- benefit organisations.

  8. The World Stress Map

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Knowledge of the stress field in the Earth's crust is a key issue for the understanding of geodynamic processes,seismic hazard assessment, and stability of underground openings such as waste disposals, tunnels, mines or wells, and reservoir management. The World Stress Map project is a collaborative project of academia,industry and governmental organizations that aims to understand the states and sources of tectonic stresses in the Earth's crust. We present the Worm Stress Map at 1:46,000,000 scale as a result of more than two decades of international collaboration. The map reveals that the first-order pattern of stress is of plate-wide scale, indicating that plate boundary forces are the major control of the stress orientations and the tectonic regime.

  9. Map usage in virtual environments

    OpenAIRE

    Cevik, Helsin

    1998-01-01

    Approved for public release; distribution is unlimited. It is neither practical nor efficient to represent virtual maps as we do for paper maps in the real world due to major differences in hardware and software capabilities and requirements. Instead, we can determine the parameters that affect virtual map representation and that help to construct a mental map, and then manipulate these parameters in order to increase the effectiveness of map representation as an aid in performing navigati...

  10. Mapping Atrial Fibrillation: 2015 Update

    OpenAIRE

    Chirag R. Barbhayia; Saurabh Kumar; Gregory F. Michaud

    2015-01-01

    Atrial fibrillation requires a trigger that initiates the arrhythmia and substrate that favors perpetuation. Cardiac mapping is necessary to locate triggers and substrate so that an ablation strategy can be optimized. The most commonly used cardiac mapping approach is isochronal or activation mapping, which aims to create a spatial model of electrical wavefront propagation. Historically, activation mapping has been successful for mapping point source and single or double wave reentrant arr...

  11. Ergodicity of polygonal slap maps

    Science.gov (United States)

    Del Magno, Gianluigi; Lopes Dias, João; Duarte, Pedro; Gaivão, José Pedro

    2014-08-01

    Polygonal slap maps are piecewise affine expanding maps of the interval obtained by projecting the sides of a polygon along their normals onto the perimeter of the polygon. These maps arise in the study of polygonal billiards with non-specular reflection laws. We study the absolutely continuous invariant probabilities (acips) of the slap maps for several polygons, including regular polygons and triangles. We also present a general method for constructing polygons with slap maps with more than one ergodic acip.

  12. Mapping your competitive position.

    Science.gov (United States)

    D'Aveni, Richard A

    2007-11-01

    A price-benefit positioning map helps you see, through your customers' eyes, how your product compares with all its competitors in a market. You can draw such a map quickly and objectively, without having to resort to costly, time-consuming consumer surveys or subjective estimates of the excellence of your product and the shortcomings of all the others. Creating a positioning map involves three steps: First, define your market to include everything your customers might consider to be your product's competitors or substitutes. Second, track the price your customers actually pay (wholesale or retail? bundled or unbundled?) and identify what your customers see as your offering's primary benefit. This is done through regression analysis, determining which of the product's attributes (as described objectively by rating services, government agencies, R&D departments, and the like) explains most of the variance in its price. Third, draw the map by plotting on a graph the position of every product in the market you've selected according to its price and its level of primary benefit, and draw a line that runs through the middle of the points. What you get is a picture of the competitive landscape of your market, where all the products above the line command a price premium owing to some secondary benefit customers value, and all those below the line are positioned to earn market share through lower prices and reduced secondary benefits. Using examples as varied as Harley-Davidson motorcycles, Motorola cell phones, and the New York restaurant market, Tuck professor D'Aveni demonstrates some of the many ways the maps can be used: to locate unoccupied or less-crowded spaces in highly competitive markets, for instance, or to identify opportunities created through changes in the relationship between the primary benefit and prices. The maps even allow companies to anticipate--and counter-- rivals' strategies. R eprint RO711G PMID:18159791

  13. Mapping the Frozen Void

    Science.gov (United States)

    Suutarinen, Aleksi; Fraser, Helen

    2013-07-01

    Reactions on the surfaces of dust grains play a vital role in the overall chemistry of interstellar matter. These grains become covered by icy layers, which are the largest molecular reservoir in the interstellar medium. Given this, it is surprising that the effect ice has on the overall chain of reactions is poorly characterized. One step on the path of gaining better understanding here is to develop methods of figuring out how much ice is present in these clouds, the links between ice components, and synergy between the ices and gas phase molecules. We do this by examining the absorption spectra of ices on lines of sight towards several stars behind clouds of interstellar matter. From these we can reconstruct spatial maps of the ice distribution on scales of as little as 1000 AU, as a test of the chemical variation within a cloud. By overlapping the ice data with other maps of the same region (gas emission, temperature, density etc) we create combined maps to reveal the astrochemistry of star-forming regions and pre-stellar cores. In this poster we present the continuing results of our ice mapping programme, using data from the AKARI satellite, specifically in slitless spectroscopy observations in the NIR. In this region the key ice features encompass H2O, CO and CO2. The maps illustrate the power of our dedicated AKARI data reduction pipeline, and the novelty of our observing programme. We also detail the next steps' in our ice mapping research. The method is being expanded to include the full 10'x10' AKARI field of view, taking account of image distortion induced by the dispersing optics. These maps are then combined with exiting gas-phase observations and SCUBA maps. The latest attempts at this are shown here. What is clear already is that it is difficult to predict ice abundances from factors such as extinction or gas density alone, and that ice formation and evolution can vary hugely over even very small astronomical scales.

  14. On occult period maps

    CERN Document Server

    Kudla, Stephen

    2012-01-01

    We consider the "occult" period maps into ball quotients which exist for the moduli spaces of cubic surfaces, cubic threefolds, non-hyperelliptic curves of genus three and four. These were constructed in the work of Allcock/Carlson/Toledo, Looijenga/Swierstra, and Kondo. We interpret these maps as morphisms into moduli spaces of polarized abelian varieties of Picard type, and show that these morphisms, whose initial construction is transcendental, are defined over the natural field of definition of the spaces involved. This paper is extracted from section 15 of our paper arXiv:0912.3758, and differs from it only in some points of exposition.

  15. Learning Bing maps API

    CERN Document Server

    Sinani, Artan

    2013-01-01

    This is a practical, hands-on guide with illustrative examples, which will help you explore the vast universe of Bing maps.If you are a developer who wants to learn how to exploit the numerous features of Bing Maps then this book is ideal for you. It can also be useful for more experienced developers who wish to explore other areas of the APIs. It is assumed that you have some knowledge of JavaScript, HTML, and CSS. For some chapters a working knowledge of .Net and Visual Studio is also needed.

  16. Computer vision mapping system

    International Nuclear Information System (INIS)

    This paper describes a system capable of accurately mapping the pipe layout (including the associated components) in an existing nuclear power plant. The system processes the images taken by a laser range finder and creates a 3D model of the existing pipe system. Accurate mapping of the geometry, location, and orientation of pipe routes as well as components will permit both the generation of the 3D CAD database and validation of as-built plants with pre-existing CAD databases. (author)

  17. Some Combined Relations between Contractive Mappings, Kannan Mappings, Reasonable Expansive Mappings, and -Stability

    Directory of Open Access Journals (Sweden)

    De la Sen M

    2009-01-01

    Full Text Available In recent literature concerning fixed point theory for self-mappings in metric spaces , there are some new concepts which can be mutually related so that the inherent properties of each one might be combined for such self-mappings. Self-mappings can be referred to, for instance, as Kannan-mappings, reasonable expansive mappings, and Picard -stable mappings. Some relations between such concepts subject either to sufficient, necessary, or necessary and sufficient conditions are obtained so that in certain self-mappings can exhibit combined properties being inherent to each of its various characterizations.

  18. eMAPS

    CERN Multimedia

    Human Resources Department

    2005-01-01

    Starting with the 2005 performance appraisal and advancement exercise (MAPS), the paper version of the annual appraisal report has been replaced by an electronic EDH version - eMAPS (see Weekly Bulletin 48/2004). As announced in Weekly Bulletin 2/2005, information sessions to explain the features of eMAPS using EDH have been arranged as follows: 18 January 2005: Main Auditorium (500-1-001) from 14:00 to 15:30. 20 January 2005: AB Auditorium II (864-1-D02) from 14:00 to 15:30. 24 January 2005: AT Auditorium (30-7-018) from 10:00 to 11:30. The changeover to an electronic appraisal report is designed to reduce the administrative workload involving, e.g. photocopying, tracing and filing paper copies, while allowing staff members and their hierarchy access to the report form at the appropriate times. There is no change in the procedure for the annual interview and the advancement exercise, though Administrative Circular No 26 (Rev. 5) has been updated to take account of the introduction of eMAPS. The content...

  19. STOCHASTIC FLOWS OF MAPPINGS

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In this paper, the stochastic flow of mappings generated by a Feller convolution semigroup on a compact metric space is studied. This kind of flow is the generalization of superprocesses of stochastic flows and stochastic diffeomorphism induced by the strong solutions of stochastic differential equations.

  20. Bisimulation from Open Maps

    DEFF Research Database (Denmark)

    Joyal, André; Nielsen, Mogens; Winskel, Glynn

    1996-01-01

    and van Glabeek and Goltz. A tie-up with open maps in a (pre)topos, as they appear in the work of Joyal and Moerdijk, brings to light a new model, presheaves on categories of pomsets, into which the usual category of labelled event structures embeds fully and faithfully. As an indication of its promise...

  1. Bisimulation and open maps

    DEFF Research Database (Denmark)

    Joyal, André; Nielsen, Mogens; Winskel, Glynn

    1993-01-01

    ), and Goltz and van Glabeek (1989). A tie-up with open maps in a (pre)topos brings to light a promising new model, presheaves on categories of pomsets, into which the usual category of labeled event structures embeds fully and faithfully. As an indication of its promise, this new presheaf model has refinement...

  2. Mapping the Field

    DEFF Research Database (Denmark)

    Goerres, Achim; Vanhuysse, Pieter

    2012-01-01

    Whereas the call for a political science based study of older people and ageing is not new (Cutler 1977; Heclo 1988), relatively little unified progress has been made so far. This chapter maps the field of generational politics and introduces our edited volume "Ageing Populations in Post-Industri...

  3. Learning maps -- Application

    International Nuclear Information System (INIS)

    The paper consists of a series of slides used in the presentation. They summarize the Root Learning Map process which is a tool that allows a company to modify its culture to improve productivity by allowing employees to have a vested interest in the outcome of the company. Educating the employees about different aspects of the organization is a major part of the process

  4. "Total Deposition (TDEP) Maps"

    Science.gov (United States)

    The presentation provides an update on the use of a hybrid methodology that relies on measured values from national monitoring networks and modeled values from CMAQ to produce of maps of total deposition for use in critical loads and other ecological assessments. Additionally, c...

  5. Personal Food System Mapping

    Science.gov (United States)

    Wilsey, David; Dover, Sally

    2014-01-01

    Personal food system mapping is a practical means to engage community participants and educators in individualized and shared learning about food systems, decisions, and behaviors. Moreover, it is a useful approach for introducing the food system concept, which is somewhat abstract. We developed the approach to capture diversity of personal food…

  6. Bipartite depolarizing maps

    Science.gov (United States)

    Lami, Ludovico; Huber, Marcus

    2016-09-01

    We introduce a 3-parameter class of maps (1) acting on a bipartite system which are a natural generalisation of the depolarizing channel (and include it as a special case). Then, we find the exact regions of the parameter space that alternatively determine a positive, completely positive, entanglement-breaking, or entanglement-annihilating map. This model displays a much richer behaviour than the one shown by a simple depolarizing channel, yet it stays exactly solvable. As an example of this richness, positive partial transposition but not entanglement-breaking maps is found in Theorem 2. A simple example of a positive yet indecomposable map is provided (see the Remark at the end of Section IV). The study of the entanglement-annihilating property is fully addressed by Theorem 7. Finally, we apply our results to solve the problem of the entanglement annihilation caused in a bipartite system by a tensor product of local depolarizing channels. In this context, a conjecture posed in the work of Filippov [J. Russ. Laser Res. 35, 484 (2014)] is affirmatively answered, and the gaps that the imperfect bounds of Filippov and Ziman [Phys. Rev. A 88, 032316 (2013)] left open are closed. To arrive at this result, we furthermore show how the Hadamard product between quantum states can be implemented via local operations.

  7. SS05 - Mind Mapping

    OpenAIRE

    Rachman, Alwy; Rapi, Amrin

    2011-01-01

    Dunia kampus adalah dunia akademis. Dunia akademis adalah dunia gagasan (dunia ide) yang terhubung dengan ilmu pengetahuan. Menjadi mahasiswa baru ibarat memasuki tahap awal dari satu dunia sebagaimana di atas, sebuah dunia yang sarat dengan informasi dari berbagai disiplin pengetahuan. Oleh karenanya, memetakan pikiran dan gagasan (mind mapping) adalah keterampilan yang diperlukan bagi siapa saja yang berhubungan dengan dunia pikiran dan gagasan.

  8. Between Maps and Territories

    DEFF Research Database (Denmark)

    Holmboe, Rasmus; Stricker, Jan Høgh

    2016-01-01

    This audio paper departs from an artwork made by Andreas Führer called The Map is Not The Territory D’Or; a score for a soundwalk in the town of Roskilde, Denmark. The basic sound materials used in the audio paper are 1) an interview in Danish with the artist, 2) a voice over of a theoretical tex...

  9. Mapping Joint Action.

    Science.gov (United States)

    Slawski, Carl

    The flow diagrams in this document provide cognitive maps to aid in synthesizing diverse areas of knowledge in a special brand of field theory. A model is presented which highlights the domains of structural functionalism (with concepts of cultural, personal and societal systems) and symbolic interactionism (with the concepts of self, sentiments…

  10. Mapping Global Citizenship

    Science.gov (United States)

    Stein, Sharon

    2015-01-01

    The demand to cultivate global citizenship is frequently invoked as central to colleges' and universities' internationalization efforts. However, the term "global citizenship" remains undertheorized in the context of U.S. higher education. This article maps and engages three common global citizenship positions--entrepreneurial, liberal…

  11. Map of the Moon

    Institute of Scientific and Technical Information of China (English)

    TANG YUANKAI

    2010-01-01

    @@ China has finished the full map of the Moon based on data obtained by its lunar probe Chang'e l,said Ouyang Ziyuan,chief scientist of China's lunar exploration program and an academician at the Chinese Academy of Sciences(CAS),at a press conference about the scientific achievements made by Chang'e1 on July 16,2010.

  12. Mapping digital media: Netherlands

    NARCIS (Netherlands)

    M. de Waal; A. Leurdijk; L. Nordeman; T. Poell

    2012-01-01

    The Mapping Digital Media project examines the global opportunities and risks created by the transition from traditional to digital media. Covering 60 countries, the project examines how these changes affect the core democratic service that any media system should provide: news about political, econ

  13. Mapping the Literature

    DEFF Research Database (Denmark)

    Boulus-Rødje, Nina

    2012-01-01

    As the utilization of various e-voting technologies has notably increased in the past few years, so has the amount of publications on experiences with these technologies. This article, will, therefore map the literature while highlighting some of the important topics discussed within the field of e...

  14. Secured Ontology Mapping

    Directory of Open Access Journals (Sweden)

    Manjula Shenoy.K

    2012-11-01

    Full Text Available Today’s market evolution and high volatility of business requirements put an increasing emphasis on theability for systems to accommodate the changes required by new organizational needs while maintainingsecurity objectives satisfiability. This is all the more true in case of collaboration and interoperabilitybetween different organizations and thus between their information systems. Ontology mapping has beenused for interoperability and several mapping systems have evolved to support the same. Usual solutionsdo not take care of security. That is almost all systems do a mapping of ontologies which are unsecured.We have developed a system for mapping secured ontologies using graph similarity concept. Here we giveno importance to the strings that describe ontology concepts ,properties etc. Because these strings may beencrypted in the secured ontology. Instead we use the pure graphical structure to determine mappingbetween various concepts of given two secured ontologies. The paper also gives the measure of accuracyof experiment in a tabular form in terms of precision, recall and F-measure.

  15. Photogrammetry and Digital Mapping

    DEFF Research Database (Denmark)

    Frederiksen, Poul

    1998-01-01

    Technical tour to Lithuania, Poland and Estonia for 13 technical staff and managers of State Land Service, HQ, Latvia. Focus on technical aspects and management of geographical data for map production and administration. Visits to state and local government organisations and newly established...

  16. Covariance mapping techniques

    Science.gov (United States)

    Frasinski, Leszek J.

    2016-08-01

    Recent technological advances in the generation of intense femtosecond pulses have made covariance mapping an attractive analytical technique. The laser pulses available are so intense that often thousands of ionisation and Coulomb explosion events will occur within each pulse. To understand the physics of these processes the photoelectrons and photoions need to be correlated, and covariance mapping is well suited for operating at the high counting rates of these laser sources. Partial covariance is particularly useful in experiments with x-ray free electron lasers, because it is capable of suppressing pulse fluctuation effects. A variety of covariance mapping methods is described: simple, partial (single- and multi-parameter), sliced, contingent and multi-dimensional. The relationship to coincidence techniques is discussed. Covariance mapping has been used in many areas of science and technology: inner-shell excitation and Auger decay, multiphoton and multielectron ionisation, time-of-flight and angle-resolved spectrometry, infrared spectroscopy, nuclear magnetic resonance imaging, stimulated Raman scattering, directional gamma ray sensing, welding diagnostics and brain connectivity studies (connectomics). This review gives practical advice for implementing the technique and interpreting the results, including its limitations and instrumental constraints. It also summarises recent theoretical studies, highlights unsolved problems and outlines a personal view on the most promising research directions.

  17. 2004 Alaska Lidar Mapping

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The data sets are generated using the OPTECH ALTM 70 kHz LIDAR system mounted onboard AeroMap's twin-engine Cessna 320 aircraft. Classified data sets such as this...

  18. Comparative wear mapping techniques

    DEFF Research Database (Denmark)

    Alcock, J.; Sørensen, Ole Toft; Jensen, S.;

    1996-01-01

    Pin surfaces were analysed by laser profilometry. Two roughness parameters, R(a) and the fractal dimension, were investigated as a first step towards methods of quantitative wear mechanism mapping. Both parameters were analysed for their relationship to the severity and prevalence of a mechanism....

  19. Comparative wear mapping techniques

    DEFF Research Database (Denmark)

    Alcock, J.; Sørensen, Ole Toft; Jensen, S.;

    1996-01-01

    Pin-on-disc tests of tungsten carbide pins against silicon carbide discs were performed and wear rate, mechanism and friction maps constructed. Correlations were observed between the wear mode and the friction of the pin-disc interface, and between the qualitative incidence of disruptive wear...

  20. USGS Imagery Only Base Map Service from The National Map

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — USGS Imagery Only is a tile cache base map of orthoimagery in The National Map visible to the 1:18,000 scale. Orthoimagery data are typically high resolution images...

  1. Habitat--Offshore of Point Reyes Map Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the habitat map of the seafloor of the Offshore of Point Reyes map area, California. The vector data file is included in...

  2. Bathymetry Offshore of Point Reyes Map Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the bathymetry and shaded-relief maps of the Offshore of Point Reyes map area, California. Raster data file is included in...

  3. Bathymetry Hillshade Offshore of Point Reyes Map Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the bathymetry and shaded-relief maps of the Offshore of Point Reyes map area, California. Raster data file is included in...

  4. Contours Offshore of Point Reyes Map Map Area, California

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This part of DS 781 presents data for the bathymetric contours for several seafloor maps of the Offshore of Point Reyes map area, California. The vector data file...

  5. More 'mapping' in brain mapping: statistical comparison of effects

    DEFF Research Database (Denmark)

    Jernigan, Terry Lynne; Gamst, Anthony C.; Fennema-Notestine, Christine;

    2003-01-01

    The term 'mapping' in the context of brain imaging conveys to most the concept of localization; that is, a brain map is meant to reveal a relationship between some condition or parameter and specific sites within the brain. However, in reality, conventional voxel-based maps of brain function, or ...

  6. Mapping or Tracing? Rethinking Curriculum Mapping in Higher Education

    Science.gov (United States)

    Wang, Chia-Ling

    2015-01-01

    Curriculum mapping has been emphasized in recent curriculum innovations in higher education in the drive for global competitiveness. This paper begins by providing an outline of current discourses of curriculum mapping in higher education. Curriculum mapping is frequently associated with outcome-based learning and work readiness, and guiding the…

  7. NEPR Geographic Zone Map 2015

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This geographic zone map was created by interpreting satellite and aerial imagery, seafloor topography (bathymetry model), and the new NEPR Benthic Habitat Map...

  8. NEPR Benthic Habitat Map 2015

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This benthic habitat map was created from a semi-automated habitat mapping process, using a combination of bathymetry, satellite imagery, aerial imagery and...

  9. Knowledge Map of Facilities Management

    DEFF Research Database (Denmark)

    Nenonen, Suvi; Jensen, Per Anker; Lindahl, Göran

    2014-01-01

    Purpose This paper aims to draft a knowledge map of the fragmented and multidisciplinary research of and relevant to FM. Facilities management knowledge map is a tool for presenting what relevant data and knowledge, a.k.a. knowledge, resides in different disciplines. Knowledge mapping is a step...... in creating an inventory of knowledge (i.e. the knowledge base) and developing/improving the processes of knowledge sharing in research, education and practice. Theory Knowledge mapping is discussed in terms of knowledge management. The research is connected to knowledge mapping in the facilities management...... profession, research and education. The knowledge map aims to contrast perspectives on how to map interdisciplinary research. Design/methodology/approach The Knowledge map is based on classification of 83 articles, including volume 2013 of Facilities (40 articles) and of Journal of Facilities Management (21...

  10. Map projections cartographic information systems

    CERN Document Server

    Grafarend, Erik W

    2006-01-01

    Offers a review of map projections (sphere, ellipsoidal, rotational surfaces) and of the geodetic datum transformations, in the context of Geographical Information Systems (GIS). This book also includes the reviews of computer vision and remote sensing space projective mappings.

  11. North America Synoptic Weather Maps

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Series of Synoptic Weather Maps. Maps contains a surface analysis comprised of plotted weather station observations, isobars indicating low and high-pressure...

  12. Mapping Deviant Democracy

    DEFF Research Database (Denmark)

    Seeberg, Michael

    2014-01-01

    A number of countries have emerged as stable (though minimalist) democracies despite low levels of modernization, lack of democratic neighbouring countries and other factors consistently related to democratic stability in the literature. The study of these deviant democracies is a promising new...... research field but it is afflicted by a notable problem, viz. the lack of a consensus as to which countries are actually instances of deviant democracy. The present article attempts to solve this problem by carrying out a comprehensive mapping of deviant democracies. First, I review the existing literature...... to provide an overview of the cases most often identified as deviant democracies. Second, I use a large-N analysis to systematically map deviant democracies. The analysis includes 159 countries covering the time period 1993–2008. The analysis points to 12 cases that merits further attention, viz...

  13. Graphene mobility mapping

    DEFF Research Database (Denmark)

    Buron, Jonas Christian Due; Pizzocchero, Filippo; Jepsen, Peter Uhd;

    2015-01-01

    Carrier mobility and chemical doping level are essential figures of merit for graphene, and large-scale characterization of these properties and their uniformity is a prerequisite for commercialization of graphene for electronics and electrodes. However, existing mapping techniques cannot directly...... assess these vital parameters in a non-destructive way. By deconvoluting carrier mobility and density from non-contact terahertz spectroscopic measurements of conductance in graphene samples with terahertz-transparent backgates, we are able to present maps of the spatial variation of both quantities over...... graphene indicates dominance by charged scatterers. Unexpectedly, significant variations in mobility rather than doping are the cause of large conductance inhomogeneities, highlighting the importance of statistical approaches when assessing large-area graphene transport properties....

  14. Diffusion Based Photon Mapping

    DEFF Research Database (Denmark)

    Schjøth, Lars; Sporring, Jon; Fogh Olsen, Ole

    2008-01-01

    . To address this problem, we introduce a photon mapping algorithm based on nonlinear anisotropic diffusion. Our algorithm adapts according to the structure of the photon map such that smoothing occurs along edges and structures and not across. In this way, we preserve important illumination features, while......Density estimation employed in multi-pass global illumination algorithms give cause to a trade-off problem between bias and noise. The problem is seen most evident as blurring of strong illumination features. In particular, this blurring erodes fine structures and sharp lines prominent in caustics...... eliminating noise. We demonstrate the applicability of our algorithm through a series of tests. In the tests, we evaluate the visual and computational performance of our algorithm comparing it to existing popular algorithms. Udgivelsesdato: December...

  15. MAPS Appraisal Report Form

    CERN Multimedia

    HR Department

    2005-01-01

    As announced in Weekly Bulletin 48/2004, from now onwards, the paper MAPS appraisal report form has been replaced by an electronic form, which is available via EDH (on the EDH desktop under Other Tasks / HR & Training) No changes have been made to the contents of the form. Practical information will be available on the web page http://cern.ch/ais/projs/forms/maps/info.htm, and information meetings will be held on the following dates: 18 January 2005: MAIN AUDITORIUM (500-1-001) from 14:00 to 15:30. 20 January 2005: AB AUDITORIUM II (864-1-D02) from14:00 to 15:30. 24 January 2005: AT AUDITORIUM (30-7-018) from 10:00 to 11:30. Human Resources Department Tel. 73566

  16. Conformal Complementarity Maps

    CERN Document Server

    Barbón, José L F

    2013-01-01

    We study quantum cosmological models for certain classes of bang/crunch singularities, using the duality between expanding bubbles in AdS with a FRW interior cosmology and perturbed CFTs on de Sitter space-time. It is pointed out that horizon complementarity in the AdS bulk geometries is realized as a conformal transformation in the dual deformed CFT. The quantum version of this map is described in full detail in a toy model involving conformal quantum mechanics. In this system the complementarity map acts as an exact duality between eternal and apocalyptic Hamiltonian evolutions. We calculate the commutation relation between the Hamiltonians corresponding to the different frames. It vanishes only on scale invariant states.

  17. Graphene Conductance Uniformity Mapping

    DEFF Research Database (Denmark)

    Buron, Jonas Christian Due; Petersen, Dirch Hjorth; Bøggild, Peter;

    2012-01-01

    We demonstrate a combination of micro four-point probe (M4PP) and non-contact terahertz time-domain spectroscopy (THz-TDS) measurements for centimeter scale quantitative mapping of the sheet conductance of large area chemical vapor deposited graphene films. Dual configuration M4PP measurements......, demonstrated on graphene for the first time, provide valuable statistical insight into the influence of microscale defects on the conductance, while THz-TDS has potential as a fast, non-contact metrology method for mapping of the spatially averaged nanoscopic conductance on wafer-scale graphene with scan times...... of less than a minute for a 4-in. wafer. The combination of M4PP and THz-TDS conductance measurements, supported by micro Raman spectroscopy and optical imaging, reveals that the film is electrically continuous on the nanoscopic scale with microscopic defects likely originating from the transfer process...

  18. Maps and statistics

    International Nuclear Information System (INIS)

    This document provides, supplying by more than 54 maps and tables, statistics on the petroleum industry and market. It covers the mine sites near Paris, in Aquitaine (France) and in north sea; the reserves; the petroleum and natural gas production in north sea; the refinery capacities; the petroleum production in CIS, North Africa, Egypt, Middle-East; the drilling activities; the turn over of petroleum, gas, para-petroleum, petrochemical industry and the industrialists; the refining in France; the chemical industry in France

  19. The grief map

    Science.gov (United States)

    Monteiro, L. H. A.

    2014-12-01

    Grieving is a natural human reaction to a significant loss. According to a psychiatric model, this process is characterized by a typical sequence of psychological changes. Here, I propose a discrete-time dynamical system, called the grief map, in order to represent the grieving process. The corresponding bifurcation diagram, which exhibits stationary, periodic, and chaotic behavior, is related to the stages of this sorrowful journey occurring during about 12 months post-loss.

  20. Mapping the cytoskeletal prestress

    OpenAIRE

    Park, Chan Young; Tambe, Dhananjay; Alencar, Adriano M.; Trepat, Xavier; Zhou, En Hua; Millet, Emil; Butler, James P.; Fredberg, Jeffrey J.

    2010-01-01

    Cell mechanical properties on a whole cell basis have been widely studied, whereas local intracellular variations have been less well characterized and are poorly understood. To fill this gap, here we provide detailed intracellular maps of regional cytoskeleton (CSK) stiffness, loss tangent, and rate of structural rearrangements, as well as their relationships to the underlying regional F-actin density and the local cytoskeletal prestress. In the human airway smooth muscle cell, we used micro...

  1. Intercreativity: Mapping Online Activism

    Science.gov (United States)

    Meikle, Graham

    How do activists use the Internet? This article maps a wide range of activist practice and research by applying and developing Tim Berners-Lee's concept of ‘intercreativity' (1999). It identifies four dimensions of Net activism: intercreative texts, tactics, strategies and networks. It develops these through examples of manifestations of Net activism around one cluster of issues: support campaigns for refugees and asylum seekers.

  2. Map of the Moon

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China releases data about the Moon collected its first lunar probe China has finished the full map of the Moon based on data obtained by its lunar probe Chang ’e 1,said Ouyang Ziyuan,chief scientist of China’s lunar exploration program and an academician at the Chinese Academy of Sciences (CAS),at a press conference about the scientific achievements made by Chang’e 1 on July 16,2010.

  3. Mapping the Literature

    DEFF Research Database (Denmark)

    Boulus-Rødje, Nina

    2012-01-01

    As the utilization of various e-voting technologies has notably increased in the past few years, so has the amount of publications on experiences with these technologies. This article, will, therefore map the literature while highlighting some of the important topics discussed within the field of......-voting. Particular attention will be paid to non-technical dimensions, including socio-cultural, organizational and political dimensions of these implementations....

  4. MAP user's manual copyright

    International Nuclear Information System (INIS)

    The program MITMAP represents a set of general purpose, two- dimensional, finite element programs for the calculation of magnetic fields. It consists of the program MAP and MAP2DJ. The two programs are used to solve different electromagnetic problems, but they have a common set of subrountines for pre- and postprocessing. Originally separate programs, they have been combined to make modification easier. The manuals, however, will remain separate. The program MAP is described in this manual. MAP is applicable to the class of problems with two-dimensional-planar or axisymmetric - geometries, in which the current density and the magnetic vector potential have only a single nonvanishing component. The single component is associated with the direction that is perpendicular to the plane of the problem and is invariant with respect to that direction. Maxwell's equations can be reduced to a solver diffusion equation in terms of the single, nonvanishing component of the magnetic vector potential for planar problems and to a single component of a vector potential for planar problems and to a single component of a vector diffusion equation for axisymmetric problems. The magnetic permeability appears in the governing equation. The permeability may be a function of the magnetic flux density. In addition, any electrically conducting material present will have eddy currents induced by a time varying magnetic field. These eddy currents must be included in the solution process. This manual provides a description of the structure of the input data and output for the program. There are several example problems presented that illustrate the major program features. Appendices are included that contain a derivation of the governing equations and the application of the finite element method to the solution of the equations

  5. Skyrmions from Harmonic Maps

    OpenAIRE

    Zakrzewski, Wojtek

    2000-01-01

    We describe some relations between solitonic solutions of various models in different dimensions. We present some examples and then concentrate on some of our recent work (performed in collaboration with Ioannidou and Piette) \\cite{IPZ} \\cite{us2} which shows how some harmonic maps from S2 to CPN-1 can be used to find nontrivial spherically symmetric static solutions of the SU(N) Skyrme model in 3 dimensions and to generate some of its low energy field configurations.

  6. Teaching and assessing mind maps

    OpenAIRE

    Jennifer Wright

    2011-01-01

    The purpose of literacy interventions in higher education is to develop students’ competencies so they could cope with the literacy demands of their academic studies. One such competency is mind mapping. The literature provides strong arguments that mind mapping provides students with valuable organisational and heuristic tools and offers guidelines on how to draw mind maps. The issue of assessing mind maps is, however, generally absent. This paper explores the characteristics of effective mi...

  7. Knowledge Map of Facilities Management

    OpenAIRE

    Nenonen, Suvi; Jensen, Per Anker; Lindahl, Göran

    2014-01-01

    Purpose This paper aims to draft a knowledge map of the fragmented and multidisciplinary research of and relevant to FM. Facilities management knowledge map is a tool for presenting what relevant data and knowledge, a.k.a. knowledge, resides in different disciplines. Knowledge mapping is a step in creating an inventory of knowledge (i.e. the knowledge base) and developing/improving the processes of knowledge sharing in research, education and practice. Theory Knowledge mapping is discussed in...

  8. System of automated map design

    International Nuclear Information System (INIS)

    Preprint 'System of automated map design' contains information about the program shell for construction of territory map, performing level line drawing of arbitrary two-dimension field (in particular, the radionuclide concentration field). The work schedule and data structures are supplied, as well as data on system performance. The preprint can become useful for experts in radioecology and for all persons involved in territory pollution mapping or multi-purpose geochemical mapping. (author)

  9. Mapping Israel/Palestine

    Directory of Open Access Journals (Sweden)

    Christine Leuenberger

    2012-01-01

    studies and the sociology of knowledge in order to analyze the social context of map-making and the content and structure of maps. The focus is on how and why British, American, and Arab online news outlets depict the contested territories of Israel and the Palestinian Territories in often varied and inconsistent ways. Certain online news sources have been accused of political biases concerning the Israeli-Palestinian conflict, which arguably translates into particular maps and map layers being included in news stories. Rather than they are being a direct and pre-determined link between map-choice and politics, however, I argue that map-making can be understood as a form of ‘situated’ practice. In other words, the newsroom brings together various actors, materials, technologies and resources that enable and constrain certain activities. It is therefore local cultures, social and interactional contingencies, and institutional and political circumstances that impact map-making and explain how and why maps may converge with or diverge from politics at any given time and place. At the same time, the choice of certain maps and map layers in terms of their focus, content, design, and detail is inevitably selective and can hereby become politically meaningful. It is thus the various textual and visual signifiers and the contextual information included in a map that can become politics by other means. Moreover, the types and sources of news stories and their maps are also co-determined by power politics, the structural inequities between the state of Israel and a Palestinian state-in-the-making, and their respective ease of access to public relations infrastructures that can reach the public at large.

  10. The MAP Propulsion Subsystem

    Science.gov (United States)

    Davis, Gary T.; Bauer, Frank H. (Technical Monitor)

    2002-01-01

    This paper describes the requirements, design, integration, test, performance, and lessons learned of NASA's Microwave Anisotropy Probe (MAP) propulsion subsystem. MAP was launched on a Delta-II launch vehicle from NASA's Kennedy Space Center on June 30, 2001. Due to instrument thermal stability requirements, the Earth-Sun L2 Lagrange point was selected for the mission orbit. The L2 trajectory incorporated phasing loops and a lunar gravity assist. The propulsion subsystem's requirements are to manage momentum, perform maneuvers during the phasing loops to set up the lunar swingby, and perform stationkeeping at L2 for 2 years. MAP's propulsion subsystem uses 8 thrusters which are located and oriented to provide attitude control and momentum management about all axes, and delta-V in any direction without exposing the instrument to the sun. The propellant tank holds 72 kg of hydrazine, which is expelled by unregulated blowdown pressurization. Thermal management is complex because no heater cycling is allowed at L2. Several technical challenges presented themselves during I and T, such as in-situ weld repairs and in-situ bending of thruster tubes to accommodate late changes in the observatory CG. On-orbit performance has been nominal, and all phasing loop, mid-course correction, and stationkeeping maneuvers have been successfully performed to date.

  11. Making maps a visual guide to map design for GIS

    CERN Document Server

    Krygier, John

    2011-01-01

    Acclaimed for its innovative use of visual material, this book is engaging, clear, and compelling-exactly how an effective map should be. Nearly every page is organized around maps and other figures (many in full color) that illustrate all aspects of map making, including instructive examples of both good and poor design choices. The book covers everything from locating and processing data to making decisions about layout, symbols, color, and type. Readers are invited to think critically about both the technical features and social significance of maps as they learn to create better maps of t

  12. The Global Trachoma Mapping Project

    OpenAIRE

    Anthony W. Solomon; Elizabeth Kurylo

    2014-01-01

    In the largest disease-mapping project ever conducted, health workers trained by the Global Trachoma Mapping Project have already examined the eyelids of more than 1 million people in nearly 1,000 districts since December 2012. The data collected are being used to create the first truly complete global map of trachoma and trichiasis, due in March 2015.

  13. Using Playground Maps for Movement

    Science.gov (United States)

    Colvin, A. Vonnie

    2016-01-01

    Many schools now decorate their outside hard surface areas with maps. These maps provide color and excitement to a playground and are a terrific teaching tool for geography. But these maps can easily be integrated into physical education as well to promote both physical activity as well as knowledge of geography. The purpose of this article is to…

  14. Genetic algorithms for map labeling

    NARCIS (Netherlands)

    Dijk, Steven Ferdinand van

    2002-01-01

    Map labeling is the cartographic problem of placing the names of features (for example cities or rivers) on the map. A good labeling has no intersections between labels. Even basic versions of the problem are NP-hard. In addition, realistic map-labeling problems deal with many cartographic constr

  15. The Map to LOINC Project

    OpenAIRE

    Khan, Agha N.; Russell, Dorothy; Moore, Catherine; Rosario, Arnulfo C.; Griffith, Stanley P.; Bertolli, Jeanne

    2003-01-01

    We describe a pilot project to standardize local laboratory test names to Logical Observation Identifier Names and Codes (LOINC) at five Indian Health Service (IHS) medical facilities. An automated mapping tool was developed to assign LOINC codes. The laboratory test names not mapped to LOINC by the mapping tool were assigned LOINC codes manually. The results achieved matched current benchmarks.

  16. Developmentally Appropriate Map Skills Instruction.

    Science.gov (United States)

    Maxim, George W.

    1997-01-01

    Describes a kindergarten/first-grade and a second-grade program for teaching map reading skills. Suggests that map- reading instruction is required to improve children's geography knowledge. Provides ideas on how to observe the environment, use photos, encourage block play, use books, share maps, construct a model of the classroom, read cardinal…

  17. The Global Trachoma Mapping Project

    Directory of Open Access Journals (Sweden)

    Anthony W Solomon

    2014-04-01

    Full Text Available In the largest disease-mapping project ever conducted, health workers trained by the Global Trachoma Mapping Project have already examined the eyelids of more than 1 million people in nearly 1,000 districts since December 2012. The data collected are being used to create the first truly complete global map of trachoma and trichiasis, due in March 2015.

  18. Geologic map of Io

    Science.gov (United States)

    Williams, David A.; Keszthelyi, Laszlo P.; Crown, David A.; Yff, Jessica A.; Jaeger, Windy L.; Schenk, Paul M.; Geissler, Paul E.; Becker, Tammy L.

    2011-01-01

    Io, discovered by Galileo Galilei on January 7–13, 1610, is the innermost of the four Galilean satellites of the planet Jupiter (Galilei, 1610). It is the most volcanically active object in the Solar System, as recognized by observations from six National Aeronautics and Space Administration (NASA) spacecraft: Voyager 1 (March 1979), Voyager 2 (July 1979), Hubble Space Telescope (1990–present), Galileo (1996–2001), Cassini (December 2000), and New Horizons (February 2007). The lack of impact craters on Io in any spacecraft images at any resolution attests to the high resurfacing rate (1 cm/yr) and the dominant role of active volcanism in shaping its surface. High-temperature hot spots detected by the Galileo Solid-State Imager (SSI), Near-Infrared Mapping Spectrometer (NIMS), and Photopolarimeter-Radiometer (PPR) usually correlate with darkest materials on the surface, suggesting active volcanism. The Voyager flybys obtained complete coverage of Io's subjovian hemisphere at 500 m/pixel to 2 km/pixel, and most of the rest of the satellite at 5–20 km/pixel. Repeated Galileo flybys obtained complementary coverage of Io's antijovian hemisphere at 5 m/pixel to 1.4 km/pixel. Thus, the Voyager and Galileo data sets were merged to enable the characterization of the whole surface of the satellite at a consistent resolution. The United States Geological Survey (USGS) produced a set of four global mosaics of Io in visible wavelengths at a spatial resolution of 1 km/pixel, released in February 2006, which we have used as base maps for this new global geologic map. Much has been learned about Io's volcanism, tectonics, degradation, and interior since the Voyager flybys, primarily during and following the Galileo Mission at Jupiter (December 1995–September 2003), and the results have been summarized in books published after the end of the Galileo Mission. Our mapping incorporates this new understanding to assist in map unit definition and to provide a global synthesis

  19. A guide of patent map

    International Nuclear Information System (INIS)

    This book introduces application and characteristic of patent information, types of patent information data and research of patent information, arrangement of patent information and patent map, analysis of patent information, necessity, writing period arrangement way of patent map, cases of patent map on selection of task of research and development, system of research and development and application, examples of PM such as MAP by year, application, technique, Inventor, and claim point map and computerization like data arrangement of PM patent, collection of analysis range and item analysis of patent, cases and written reports on patent analysis.

  20. Mapping the human protein interactome

    Institute of Scientific and Technical Information of China (English)

    Daniel Figeys

    2008-01-01

    Interactions are the essence of all biomolecules because they cannot fulfill their roles without interacting with other molecules. Hence, mapping the interactions of biomolecules can be useful for understanding their roles and functions. Furthermore, the development of molecular based systems biology requires an understanding of the biomolecular interactions. In recent years, the mapping of protein-protein interactions in different species has been reported, but few reports have focused on the large-scale mapping of protein-protein interactions in human. Here, we review the developments in protein interaction mapping and we discuss issues and strategies for the mapping of the human protein interactome.