Romero-Sánchez Marisa, Peiper Stephen C, Evans Barry, Wang Zixuan, Catasús Lluis, Ribe Adriana, Prat Jaime, Giri Judith G
Hospital de la Santa Creu i Sant Pau, Autonomous University, 08025 Barcelona, Spain.
Hum Pathol. 2008 Jul;39(7):1026-33. doi: 10.1016/j.humpath.2007.11.007. Epub 2008 May 13.
A novel class of putative progestin binding proteins has been recently identified as potential mediators of rapid nongenomic hormone actions. The proteins designated membrane progestin receptor (mPR) alpha, beta, and gamma were initially discovered in fish and shown to have a role in oocyte maturation. The predicted multiple membrane spanning domain structure of the mPRs resembles that of heptahelical G-protein-coupled receptors. Phylogenetic analysis indicated that the mPRs belong to the large progestin and adiponectin Q receptor (PAQR) gene family. Based on the reported expression of the 3 mPRs in hormone-responsive tissues of the female reproductive tract and on the role of steroid hormones in cancer, we investigated the expression of these novel progestin receptors in epithelial tumors of the ovary. The transcript levels of the 3 human mPR/PAQRs were assessed by semiquantitative reverse transcriptase polymerase chain reaction in 28 ovarian samples, including normal tissues, cystadenomas, borderline tumors, and common types of ovarian carcinomas. Two of the 3 transcripts for the mPR/PAQRs proteins appeared differentially expressed in the tumors examined. Expression of mPR alpha and beta was demonstrated in ovarian tumors at both messenger RNA and protein level, and their expression appeared to be independent of the expression of the classic nuclear progestin receptors. Expression of mPR gamma (PAQR V) was elevated in endometrioid and clear cell carcinomas, 2 related neoplastic counterparts of hormonally responsive tissues, suggesting a potential role of the mPR/PAQRs in the pathogenesis of epithelial ovarian tumors.
最近,一类新的假定孕激素结合蛋白被确定为快速非基因组激素作用的潜在介质。被命名为膜孕激素受体(mPR)α、β和γ的这些蛋白最初在鱼类中被发现,并显示在卵母细胞成熟中起作用。mPRs预测的多个跨膜结构域结构类似于七螺旋G蛋白偶联受体。系统发育分析表明,mPRs属于大的孕激素和脂联素Q受体(PAQR)基因家族。基于报道的3种mPRs在女性生殖道激素反应性组织中的表达以及类固醇激素在癌症中的作用,我们研究了这些新型孕激素受体在卵巢上皮性肿瘤中的表达。通过半定量逆转录聚合酶链反应在28个卵巢样本中评估了3种人类mPR/PAQRs的转录水平,这些样本包括正常组织、囊腺瘤、交界性肿瘤和常见类型的卵巢癌。在所检测的肿瘤中,mPR/PAQRs蛋白的3种转录本中有2种表现出差异表达。mPRα和β在卵巢肿瘤的信使核糖核酸和蛋白水平均有表达,并且它们的表达似乎与经典核孕激素受体的表达无关。mPRγ(PAQR V)在子宫内膜样癌和透明细胞癌(两种激素反应性组织的相关肿瘤对应物)中表达升高,提示mPR/PAQRs在上皮性卵巢肿瘤发病机制中可能起作用。