Augmentation of estrogen receptor-mediated transcription by steroid and xenobiotic receptor

作者：Rokutanda Nana; Iwasaki Toshiharu^*; Odawara Hiroki; Nagaoka Rin; Miyazaki Wataru; Takeshita Akira; Koibuchi Yukio; Horiguchi Jun; Shimokawa Noriaki; Lino Yuichi; Morishita Yasuo; Koibuchi Noriyuki

来源：Endocrine, 2008, 33(3): 305-316.

DOI：10.1007/s12020-008-9091-9

• Estrogen receptor
• Steroid and xenobiotic receptor
• Breast cancer
• SMRT

The estrogen receptor (ER) is a key regulator of proliferation and differentiation in breast cancer cells. In the present study, the effect of steroid and xenobiotic receptor (SXR) on 17 beta-estradiol (E(2))-induced transcription through ER alpha was studied. SXR augmented ER-mediated transcription in the presence of E2 in MCF-7 breast cancer-derived cells and CV-1 fibroblast-derived cells. On the other hand, SXR alone did not affect the estrogen response element (ERE)-containing promoter activity in CV-1 cells. SXR did not directly bind to ER alpha or ERE in vitro, indicating that SXR may affect ER-mediated transcription by altering cofactor binding to ER. Although SXR did not alter the binding between ERa and p300/CBP interacting protein (p/CIP), it decreased the binding of a specific corepressor, silencing mediator of retinoid and thyroid hormone receptors (SMRT) to liganded ER alpha as assessed by mammalian two-hybrid, glutathione S-transferase pull-down, immunoprecipitation and newly developed Liquid Chemiluminescent DNA Pull-Down Assays. These results indicate that SXR augmented ER-mediated transcription by dissociating SMRT from ER alpha. Thus, the expression of SXR in breast cancer cells may alter the ER signaling, which may play crucial role for growth and differentiation of breast cancer cells.

• 出版日期2008-6
• 单位河北医科大学