title: Histone 3 Trimethylation of IGFBP-7 Gene Promoter by Expression of D5 Stat5a in Breast Epithelial Cells.
abstract: 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.
authors.affiliation: Institute of Medical Sciences, Jishou University School of Medicine, Hunan, People's Republic of China.
authors.forename: Dunyong
authors.initials: D
authors.lastname: Tan
authors.affiliation: Institute of Medical Sciences, Jishou University School of Medicine, Hunan, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Medical Sciences, Jishou University School of Medicine, Hunan, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Nie
authors.affiliation: Institute of Medical Sciences, Jishou University School of Medicine, Hunan, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.affiliation: Institute of Medical Sciences, Jishou University School of Medicine, Hunan, People's Republic of China.
authors.forename: Zhongzheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Medical Sciences, Jishou University School of Medicine, Hunan, People's Republic of China.
authors.forename: Zulbnur
authors.initials: Z
authors.lastname: Mamat
authors.affiliation: Institute of Medical Sciences, Jishou University School of Medicine, Hunan, People's Republic of China.
authors.forename: Huang
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Institute of Medical Sciences, Jishou University School of Medicine, Hunan, People's Republic of China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Medical Sciences, Jishou University School of Medicine, Hunan, People's Republic of China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Medical Sciences, Jishou University School of Medicine, Hunan, People's Republic of China.
authors.forename: Sihong
authors.initials: S
authors.lastname: Yao
authors.affiliation: Jishou University First Affiliated Hospital, Department of Breast Surgery, Jishou 416000, Hunan, People's Republic of China.
authors.forename: Peizhi
authors.initials: P
authors.lastname: Tang
authors.affiliation: Jishou University First Affiliated Hospital, Department of Breast Surgery, Jishou 416000, Hunan, People's Republic of China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Huang
mesh_terms: D000071221:Enhancer of Zeste Homolog 2 Protein; D004847:Epithelial Cells / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D061986:MCF-7 Cells; D008745:Methylation; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D050799:STAT5 Transcription Factor / Q000378:metabolism*
chemical_list: D006657:Histones; D018969:Insulin-Like Growth Factor Binding Proteins; D050799:STAT5 Transcription Factor; C102529:insulin-like growth factor binding protein-related protein 1; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2