【摘 要】
：
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 no
【机 构】
：
Kunming Institute of Zoology.Chinese Academy of Sciences China
【出 处】
：
BITs 3rd Annual World Cancer Congress-2012(2012第五届世界癌症大会)
论文部分内容阅读
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 Krupple-like factor 5 (KLF5), a pro-proliferation 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 multiplePg receptor (PR)-positive breast cancer cell lines.Pg induced the KLF5 transcription through PR in the PR-positive T47D breast cancer cells.Pg-activated PR increased the KLF5 promoter activity likely through binding to a Pg response element at the KLF5 promoter.Importantly, Pg failed to promote T47D cell proliferation when the KLF5 induction was blocked by small interfering RNA.KLF5 is essential for Pg to up-regulate the expression of cell cycle genes, including CyclinA, Cdt1, and E2F3.In addition, KLF5 overexpression was sufficient to induce the cytokeratin 5 (CK5) expression, and the induction of CK5 by Pg was significantly reduced by KLF5 small interfering RNA.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 dedifferentiation.
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