题名

Histone 3 Trimethylation of IGFBP-7 Gene Promoter by Expression of D5 Stat5a in Breast Epithelial Cells

DOI

10.4077/CJP.2015.BAD322

作者

Dun-Yong Tan；Jie Zhang；Xi Nie；Chao Yu；Zhong-Zheng Li；Zulbnur Mamat；Huang Jiang；Xiao-Meng Yang；Jiao Zhang；Sihong Yao；Peizhi Tang；Jian-Jun Huang

关键词

breast cancer ； chromatin immunoprecipitation assay (ChIP) ； D5 Stat5a ； H3K27Me3 ； histone modification ； IGFBP-7

期刊名称

The Chinese Journal of Physiology

卷期/出版年月

58卷5期（2015 / 10 / 31）

页次

275 - 284

内容语文

英文
英文摘要

As a very important transcription factor, signal transducer and activator of transcription 5a (Stat5a) has been reported to be involved in human reproductive cancers such as breast, prostate and ovarian cancer. However, up to date, the exact role of Stat5a in breast cancer is still not clear. The data reported are conflicting. D5 Stat5a is a variant of Stat5a we cloned recently. This newly cloned variant behave like its full length counterpart in terms of dimerization, being activated by prolactin and nuclear translocation, however it also behave differently in terms of effect on cell proliferation and interaction with other transcription factors. In the present study, we examined its effect on cell proliferation of cultured breast cancer cells (MCF-10A and MCF-7) by using adenovirus-mediated gene transfer and MTS technology. Also, quantitative real time polymerase chain reaction (qRT-PCR), chromatin immunoprecipitation assay (ChIP) and Western blot were used to probe the possible changes of insulin-like growth factor binding protein-7 (IGFBP-7) expression including mRNA and protein, and the epigenetic changes with overexpression of this newly cloned variant. The results clarified that D5 Stat5a (1) behaves as a promoting factor to the cell proliferation of MCF-10A and MCF-7, (2) induces enhancer of zeste homology 2 (EZH2) expression in breast epithelial cells, as well as histone 3 trimethylation of IGFBP-7 promoter region, and (3) lower IGFBP-7 expression was detected in breast cancer tissue. Taking together, we concluded that the mitogenic effect of D5 Stat5a on breast cells is, at least partly, through up-regulation of histone methyltransferase, EZH2, and therefore inhibiting IGFBP-7 expression by increasing H3K27Me3 of IGFBP-7 promoter region.
主题分类 醫藥衛生 > 基礎醫學
参考文献
  1. Lin, Y.M.,Su, C.C.,Su, W.W.,Hwang, J.M.,Hsu, H.H.,Tsai, C.H.,Wang, Y.C.,Tsai, F.J.,Huang, C.Y.,Liu, J.Y.,Chen, L.M.(2012).Expression of protein kinase C isoforms in cancerous breast tissue and adjacent normal breast tissue.Chinese J. Physiol.,55,55-61.
    連結：
  2. Wang, J.L.,Sun, S.Z.,Qu, X.,Liu, W.J.,Wang, Y.Y.,Lv, C.X.,Sun, J.Z.,Ma, R.(2011).Clinicopathological significance of CEACAM1 gene expression in breast cancer.Chinese J. Physiol.,54,332-338.
    連結：
  3. Yue, C.H.,Chiu, Y.W.,Tung, J.N.,Tzang, B.S.,Shiu, J.J.,Huang, W.H.,Liu, J.Y.,Hwang, J.M.(2012).Expression of protein kinase C α and the MZF-1 and Elk-1 transcription factors in human breast cancer cells.Chinese J. Physiol.,55,31-36.
    連結：
  4. Akira, S.(1999).Functional roles of STAT family proteins: lessons from knockout mice.Stem Cells,17,138-146.
  5. Bannister, A.J.,Kouzarides, T.(2011).Regulation of chromatin by histone modifications.Cell Res.,21,381-395.
  6. Barros, P.,Lam, E.W.F.,Jordan, P.(2012).Rac1 signalling modulates a STAT5/BCL-6 transcriptional switch on cell-cycle-associated target gene promoters.Nucleic Acids Res.,40,7776-7787.
  7. Benatar, T.,Yang, W.,Amemiya, Y.,Evdokimova, V.,Kahn, H.,Holloway, C.,Seth, A.(2012).IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways.Breast Cancer Res. Treat.,133,563-573.
  8. Bradley, H.L.,Couldrey, C.,Bunting, K.D.(2004).Hematopoietic-Hematopoieticrepopulating defects from STAT5-deficient bone marrow are not fully accounted for by loss of thrombopoietin responsiveness.Blood,103,2965-2972.
  9. Cedar, H.,Bergman, Y.(2009).Linking DNA methylation and histone modification: patterns and paradigms.Nat. Rev. Genet.,10,295-304.
  10. Chen, D.,Siddiq, A.,Emdad, L.,Rajasekaran, D.,Gredler, R.,Shen, X.N.,Santhekadur, P.K.,Srivastava, J.,Robertson, C.L.,Dmitriev, I.,Kashentseva, E.A.,Curiel, D.T.,Fisher, P.B.,Sarkar, D.(2013).Insulinlike growth factor-binding protein-7 (IGFBP7): a promising gene therapeutic for hepatocellular carcinoma (HCC).Mol. Ther.,21,758-766.
  11. Cheutin, T.,Cavalli, G.(2012).Progressive polycomb assembly on H3K27me3 compartments generates polycomb bodies with developmentally regulated motion.PloS Genet.,8,e1002465.
  12. Clevenger, C.V.(2004).Roles and regulation of Stat family transcription factors in human breast cancer.Am. J. Pathol.,165,1449-1460.
  13. Gu, L.,Vogiatzi, P.,Puhr, M.,Dagvadorj, A.,Lutz, J.,Ryder, A.,Addya, S.,Fortina, P.,Cooper, C.,Leiby, B.,Dasgupta, A.,Hyslop, T.,Bubendorf, L.,Alanen, K.,Mirtti, T.,Nevalainen, M.T.(2011).Stat5 promotes metastatic behavior of human prostate cancer cells in vitro and in vivo.Endocr. Relat. Cancer,17,481-493.
  14. Horseman, N.D.,Zhao, W.,Montecino-Rodriguiez, E.,Tanaka, M.,Nakashima, K.,Engle, S.J.,Smith, F.,Markoff, E.,Dorshkind, K.(1997).Defective mammopoiesis, but normal hematopoiesis, in mice with a targeted disruption of the prolactin gene.EMBO J.,16,6926-6935.
  15. Hosui, A.,Kimura, A.,Yamaji, D.,Zhu, B.M.,Na, R.,Hennighausen, L.(2009).Loss of STAT5 causes liver fibrosis and cancer development through increased TGF-β and STAT3 activation.J. Exp. Med.,206,819-831.
  16. Ikeda, K.,Nakajima, H.,Suzuki, K.,Watanabe, N.,Kagami, S.I.,Iwamoto, I.(2005).Stat5a is essential for the proliferation and survival of murine mast cells.Int. Arch. Allergy Immunol.,137,45-50.
  17. Kalita, A.,Gupta, S.,Singh, P.,Surolia, A.,Banerjee, K.(2013).IGF-1 stimulated upregulation of cyclin D1 is mediated via STAT5 signaling pathway in neuronal cells.IUBMB Life,65,462-471.
  18. Kleer, C.G.,Cao, Q.,Varambally, S.,Shen, R.,Ota, I.,Tomlins, S.A.,Ghosh, D.,Sewalt, R.G.A.B.,Otte, A.P.,Hayes, D.F.,Sabel, M.S.,Livant, D.,Weiss, S.J.,Rubin, M.A.,Chinnaiyan, A.M.(2003).EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells.Proc. Natl. Acad. Sci. USA,100,11606-11611.
  19. Li, H.,Ahonen, T.J.,Alanen, K.,Xie, J.,LeBaron, M.J.,Pretlow, T.G.,Ealley, E.L.,Zhang, Y.,Nurmi, M.,Singh, B.,Martikainen, P.M.,Nevalainen, M.T.(2004).Activation of signal transducer and activator of transcription 5 in human prostate cancer is associated with high histological grade.Cancer Res.,64,4774-4782.
  20. Liu, X.,Robinson, G.W.,Wagner, K.U.,Garrett, L.,Wyhshaw-Boris, A.,Henninghausen, L.(1997).Stat5a is mandatory for adult mammary gland development and lactogenesis.Genes Dev.,11,179-186.
  21. Martini, M.,Hohaus, S.,Petrucci, G.,Cenci, T.,Pierconti, F.,Massini, G.,Teofili, L.,Leone, G.,Larocca, L.M.(2008).Phosphorylated STAT5 represents a new possible prognostic marker in Hodgkin lymphoma.Am. J. Clin. Pathol.,129,472-477.
  22. Nagy, Z.S.,Wang, Y.,Erwin-Cohen, R.A.,Aradi, J.,Monia, B.,Wang, L.H.,Stepkowski, S.M.,Rui, H.,Kirken, R.A.(2002).Interleukin-2 family cytokines stimulate phosphorylation of the Pro-Ser-Pro motif of Stat5 transcription factors in human T cells: resistance to suppression of multiple serine kinase pathways.J. Leukoc. Biol.,72,819-828.
  23. Nevalainen, M.T.,Ahonen, T.J.,Yamashita, H.,Chandrashekar, V.,Bartke, A.,Grimley, P.M.,Robinson, G.W.,Hennighausen, L.,Rui, H.(2000).Epithelial defect in prostates of Stat5a-null mice.Lab. Invest.,80,993-1006.
  24. Nevalainen, M.T.,Xie, J.,Torhorst, J.,Bubendorf, L.,Haas, P.,Kononen, J.,Sauter, G.,Rui, H.(2004).Signal transducer and activator of transcription-5 activation and breast cancer prognosis.J. Clin. Oncol.,22,2053-2060.
  25. Okayama, Y.,Kawakami, T.(2006).Development, migration, and survival of mast cells.Immunol. Res.,34,97-115.
  26. Östlund, H.,Burger, A.,Seth, A.,Landberg, G.(2000).IGFBP-7 expression in human breast cancer and association with proliferation and cell cycle aberrations. (Abstract 02).Second International Symposium on the Molecular Biology of Breast Cancer,Lillehammer, Norway:
  27. Ren, S.,Cai, H.R.,Li, M.,Furth, P.A.(2002).Loss of Stat5a delays mammary cancer progression in a mouse model.Oncogene,21,4335-4339.
  28. Song, C.X.,He, C.(2012).Balance of DNA methylation and demethylation in cancer development.Genome Biol.,13,173.
  29. Sultan, A.S.,Xie, J.,LeBaron, M.J.,Ealley, E.L.,Nevalainen, M.T.,Rui, H.(2005).Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells.Oncogene,24,746-760.
  30. Szyf, M.(2012).DNA methylation signatures for breast cancer classification and prognosis.Genome Med.,4,26.
  31. Tan, D.Y.,Chen, K.H.E.,Deng, C.H.,Tang, P.Z.,Huang, J.J.,Mansour, T.,Luben, R.A.,Walker, A.M.(2014).An N-terminal splice variant of human Stat5a that interacts with different transcription factors is the dominant form expressed in invasive ductal carcinoma.Cancer Lett.,346,148-157.
  32. Tan, D.Y.,Johnson, D.A.,Wu, W.,Zeng, L.F.,Chen, Y.H.,Chen, W.Y.,Vonderhaar, B.K.,Walker, A.M.(2005).Unmodified prolactin (PRL) and S179D PRL-initiated bioluminescence resonance energy transfer between homo- and hetero-pairs of long and short human PRL receptors in living human cells.Mol. Endocrinol.,19,1291-1303.
  33. Tan, D.Y.,Zhang, J.,Tang, P.Z.,Huang, J.J.,Walker, A.M.(2013).Association of D5 Stat5a induced breast cancer cell migration increased H3K27 trimethylation and down-regulated expression E-cadherin gene.Adapt. Med.,5,189-195.
  34. Thomas, C.,Zoubeidi, A.,Kuruma, H.,Fazli, L.,Lamoureux, F.,Beraldi, E.,Monia, B.P.,MacLeod, A.R.,Thüroff, J.W.,Gleave, M.E.(2011).Transcription factor Stat5 knockdown enhances androgen receptor degradation and delays castration-resistant prostate cancer progression in vivo.Mol. Cancer Ther,10,347-359.
  35. Wagner, K.U.,Rui, H.(2008).Jak2/Stat5 signaling in mammogenesis, breast cancer initiation and progression.J. Mammary Gland Biol. Neoplasia,13,93-103.
  36. Walsh, L.A.,Damjanovski, S.(2011).IGF-1 increases invasive potential of MCF 7 breast cancer cells and induces activation of latent TGF-β1 resulting in epithelial to mesenchymal transition.Cell Commun. Signal.,9,10.
  37. Watson, C.J.(2001).Stat transcription factors in mammary gland development and tumorigenesis.J. Mammary Gland Biol. Neoplasia,6,115-127.
  38. Woelfle, J.,Rotwein, P.(2004).In vivo regulation of growth hormonestimulated gene transcription by STAT5b.Am. J. Physiol. Endocrinol. Metab.,286,E393-E401.
  39. Yoo, K.H.,Hennighausen, L.(2012).EZH2 methyltransferase and H3K27 methylation in breast cancer.Int. J. Biol. Sci.,8,59-65.
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