유방암 세포와 간암세포에 있어서 에스트로겐 수용체의 전사조절기능에 대한 Xenobiotic 핵 수용체 (Constitutive Androstane Receptor, Steroid and Xenobiotic Receptor, Peroxisome-Proliferator-Activated Receptorγ)의 영향 비교분석

The purpose of this study was to examine the effects of xenobiotic nuclear receptors, CAR, SXR, and PPARγ on the transcriptional activity of estrogen receptor in human breast cancer cell lines and compare with those in human hepatoma cell line. Two different breast cancer cell lines, MCF-7 and MDA-MB-231 were cultured and effects of CAR, SXR, and PPARγon the ER-mediated transcriptional activation of synthetic (4ERE)-tk-luciferase reporter gene were analyzed. Consistent with the previous report, CAR significantly inhibited ER-mediated transactivation and SXR repressed modestly whereas the PPARγ did not repress the ER-mediated transactivation. However, in breast cancer cells neither of the xenobiotic receptors repressed the ER-mediated transactivation. Instead, they tend to increase the transactivation depending on the cell type and xenobiotic nuclear receptors. In MCF-7, SXR but neither CAR nor PPARγ slightly increased ER-mediated transactivation whereas in MDA-MB-231, CAR and PPARγ but not SXR tend to increase the transactivation of the reporter gene. These results indicate that the effects of ER cross-talk by the CAR, SXR, and PPARγ, are different in breast cancer cells from hepatoma cells. In conclusion, the transcriptional regulation by estrogen can involve different cross-talk interaction between estrogen receptor and xenobiotic nuclear receptors depending on the estrogen target cells.