Estrogen regulated expression of the p21 Waf1/Cip1 gene in estrogen receptor positive human breast cancer cells

摘要: The cyclin-dependent kinase inhibitor protein p21(Waf1/Cip1) is a potent tumor suppressor. Here, we demonstrate that estradiol regulates the gene. Estradiol induces mRNA expression within 30-60 min independent of new synthesis in estrogen receptor alpha (ER alpha) positive human breast cancer cell line MCF-7. Similar to other responsive promoters, upstream promoter region has several response element (ERE) half-sites nestled AP-1 binding sites, which are positioned Sp1 sites. Using chromatin immunoprecipitation (ChIP) assay, show stimulation resulted recruitment transcription factors ER alpha, Sp1, and Sp3 element. mithramycin A abrogated lesser extent binding, markedly reduced stimulated gene expression. However, was not affected treated cells. On closer examination half-site ERE/AP-1 sites separate ChIP experiment, found pronounced association upon treatment compared almost negligible or Sp3. Together these studies provide evidence recruited Although Sp1/Sp3 involved promoter, necessary for estrogen-induced activity.