Abstract 4544: The induction of KLF5 transcription factor by progesterone contributes to progesterone-induced breast cancer cell proliferation and de-differentiation

Abstract

Abstract Progesterone (Pg) promotes normal breast development during pregnancy and lactation and increases the risk of developing basal-type invasive breast cancer. However, the mechanism of action of Pg has not been fully understood. In this study, we demonstrate that the mRNA and protein expression of Klf5, a pro-proliferation and pro-survival transcription factor in breast cancer, was dramatically up-regulated in mouse pregnant and lactating mammary glands. Pg, but not estrogen and prolactin, induced the expression of KLF5 in multiple Pg receptor (PR)-positive breast cancer cell lines. Pg induced the KLF5 transcription is through PR in the PR-positive T47D breast cancer cells. Importantly, Pg failed to promote T47D cell proliferation when the KLF5 induction was blocked by siRNA. In addition, KLF5 overexpression was sufficient to induce the cytokeratin 5 (CK5) expression and the induction of CK5 by Pg was partially abrogated by KLF5 siRNA. Consistently, the expression of KLF5 was positively correlated with that of CK5 in a panel of breast cancer cell lines. Taken together, we conclude that KLF5 is a Pg-induced gene that contributes to Pg-mediated breast epithelial cell proliferation and de-differentiation. This work was supported by a grant from the American Cancer Society (RSG-08-199-01) and a grant from the Department of Defense (W81XWH-07-1-0191). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4544. doi:10.1158/1538-7445.AM2011-4544