The nuclear receptors SF1 and LRH1 are expressed in endometrial cancer cells and regulate steroidogenic gene transcription by cooperating with AP-1 factors
The nuclear receptors SF1 and LRH1 are expressed in endometrial cancer cells and regulate steroidogenic gene transcription by cooperating with AP-1 factors
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DOI：
10.1016/j.canlet.2008.10.008
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发表时间：
2009-03-08
期刊：
影响因子：
9.7
通讯作者：
Tremblay, Jacques J.
中科院分区：
文献类型：
--
作者：
Dube, Charlotte;Bergeron, Francis;Tremblay, Jacques J.
过量暴露于雌二醇是子宫内膜癌的主要危险因素。子宫内膜癌患者的子宫内膜中异常高的雌二醇水平很可能是由于卵巢本身产生过量。子宫内膜癌细胞表达编码雌二醇合成中涉及的类固醇生成酶的基因。在这里，我们使用RT-PCR和蛋白质印迹显示，核受体SF 1和LRH 1，两个众所周知的调节类固醇基因表达的性腺和肾上腺细胞，也表达在子宫内膜癌细胞系。通过瞬时转染，我们发现SF 1和LRH 1，而不是相关的核受体β 77，可以激活三个人类固醇基因的启动子：星星，HSD 3B 2和CYP 19 A1 PII。同样，毛喉素（而不是PMA）可以激活所有三个启动子。此外，我们发现SF 1和LRH 1都可以与AP-1家族成员c-JUN和c-FOS（已知与子宫内膜癌细胞增殖增强相关）在转录上合作，以进一步增强星星、HSD 3B 2和CYP 19 A1 PII启动子的激活。总之，我们的数据提供了新的见解类固醇基因在子宫内膜癌细胞的表达机制，从而在调节雌二醇生物合成的肿瘤细胞。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Excessive exposure to estradiol represents the main risk factor for endometrial cancer. The abnormally high estradiol levels in the endometrium of women with endometrial cancer are most likely due to overproduction by the turnout itself Endometrial cancer cells express the genes encoding the steroidogenic enzymes involved in estradiol synthesis. Here we used RT-PCR and Western blot to show that the nuclear receptors SF1 and LRH1, two well-known regulators of steroidogenic gene expression in gonadal and adrenal cells, are also expressed in endometrial cancer cell lines. By transient transfections, we found that SF1 and LRH1, but not the related nuclear receptor NUR77, can activate the promoters of three human steroidogenic genes: STAR, HSD3B2, and CYP19A1 PII. Similarly, forskolin but not PMA, could activate all three promoters. In addition, we found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters. All together, our data provide novel insights into the mechanisms of steroidogenic gene expression in endometrial cancer cells and thus in the regulation of estradiol biosynthesis by tumour cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved.