title: Upregulation of ATBF1 by progesterone-PR signaling and its functional implication in mammary epithelial cells.
abstract: Progesterone (Pg) is an essential steroid hormone during mammary gland development and tumorigenesis, including the maintenance of epithelial stem/progenitor cells. Pg functions through interaction with the progesterone receptors (PR) and Pg-PR signaling is thought to be mediated by key transcription factors, which are largely unidentified. In this study, we have identified the ATBF1 transcription factor as a transcriptional target of Pg-PR signaling in mammary epithelial cells. Pg treatment dramatically increased ATBF1 expression at both mRNA and protein levels in cultured cells and mammary tissues. As expected, the induction of ATBF1 was PR-dependent, as it only occurred in PR-positive but not in PR-negative cells, and pretreatment with the Pg antagonist RU-486 or RNAi-mediated knockdown of PR abolished the upregulation of ATBF1 by Pg. Promoter-reporter and ChIP assays further showed that Pg-activated PR directly binds to the ATBF1 promoter to induce its transcription. Prevention of ATBF1 induction inhibited the function of Pg in promoting progenitor cell transition, as indicated by colony formation in a Matrigel culture assay and expression of stem cell markers CD49f and CD44. These findings suggest that ATBF1 plays a crucial role in the Pg-PR signaling pathway in mammary epithelial cells.
authors.affiliation: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Gui
authors.initials: G
authors.lastname: Ma
authors.forename: Baotong
authors.initials: B
authors.lastname: Zhang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Fu
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Zhu
authors.forename: Liya
authors.initials: L
authors.lastname: Fu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Dong
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D042361:Mammary Glands, Human / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D018398:Homeodomain Proteins; D006727:Hormone Antagonists; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone; C071660:ZFHX3 protein, human; D015735:Mifepristone; D011374:Progesterone