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.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Li M,Zhao D,Ma G,Zhang B,Fu X,Zhu Z,Fu L,Sun X,Dong JTdoi
10.1016/j.bbrc.2012.11.009subject
Has Abstractpub_date
2013-01-04 00:00:00pages
358-63issue
1eissn
0006-291Xissn
1090-2104pii
S0006-291X(12)02159-6journal_volume
430pub_type
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