Roles of steroid and xenobiotic receptor (SXR) on ER-mediated transcription in breast cancer cells

雌激素受体（ER）是乳腺癌细胞增殖和分化的关键调节因子。类固醇和异生素受体（Steroid and xenobiotic receptor，SXR）在肝脏和小肠中高度表达，并调节细胞色素P450单加氧酶3A 4（CYP 3A 4）和多药耐药基因1（multidrug resistance 1，MDR 1）编码的P-糖蛋白（P-gp）的表达。SXR也在正常和肿瘤性乳腺组织中表达。在本研究中，类固醇和异生素受体（SXR）的影响，17。雌二醇（E）通过ER诱导2转录。研究了在MCF-7乳腺癌衍生细胞和CV-1成纤维细胞衍生细胞中，SXR增强了E存在下ER介导的转录。SXR不直接与ER结合。或ERE 2的转录水平，表明SXR可能通过改变与ER结合的辅因子而影响ER介导的转录。虽然SXR没有改变ER之间的结合。和p300/CBP相互作用蛋白（p/CIP），它减少了特定辅抑制子、类维生素A和甲状腺激素受体（SMRT）的沉默介体与配体ER的结合。如通过哺乳动物双杂交、GST下拉、免疫印迹和新开发的液体化学发光DNA下拉测定所评估的。这些结果表明，SXR增强ER介导的转录，从ER解离SMRT。因此，SXR在乳腺癌细胞中的表达可能改变ER信号，这可能对乳腺癌细胞的生长和分化起关键作用。我们使用SXR启动子进行实时定量RT-PCR研究。在ER阳性、PgR阳性、HER 2阴性、无淋巴结转移、低分化的乳腺癌中，SXR mRNA的表达明显增高。

The estrogen receptor (ER) is a key regulator of proliferation and differentiation in breast cancer cells. Steroid and xenobiotic receptor (SXR) is highly expressed in the liver and small intestine and regulates the expression of cytochrome P450 monooxygenase 3A4 (CYP3A4) and P-glycoprotein (P-gp) that is encoded by multidrug resistance 1 (MDR1) gene. SXR is also expressed in normal and neoplastic breast tissue. In the present study, the effect of steroid and xenobiotic receptor (SXR) on 17.-estradiol (E)-induced 2 transcription through ER. was studied. SXR augmented ER-mediated transcription in the presence of E in MCF-7 breast cancer-derived cells and CV-1 fibroblast-derived cells. SXR did not directly bind to ER. or ERE 2in vitro, indicating that SXR may affect ER-mediated transcription by altering cofactor biding to ER. Although SXR did not alter the binding between ER. 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. as assessed by mammalian two-hybrid, GST pull down, immunoprecipiation and newly developed Liquid Chemiluminescent DNA Pull Down Assays. These results indicate that SXR augmented ER-mediated transcription by dissociating SMRT from ER. 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. We performed realtime quantitative RT-PCR studies using SXR promoter. The expression of SXR mRNA was increased in those cases ER positive, PgR positive, HER2 negative, without node metastasis, and low grade.