Progesterone signaling mediated through progesterone receptor membrane component-1 in ovarian cells with special emphasis on ovarian cancer.
Progesterone signaling mediated through progesterone receptor membrane component-1 in ovarian cells with special emphasis on ovarian cancer.
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DOI：
10.1016/j.steroids.2011.02.011
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发表时间：
2011-08
期刊：
影响因子：
2.7
通讯作者：
Peluso, John J.
中科院分区：
文献类型：
--
作者：
Peluso, John J.
各种类型的卵巢细胞，包括颗粒细胞和卵巢表面上皮细胞，都表达孕酮(P4)结合蛋白-孕酮受体膜组分-1(PGRMC1)。PGRMC1在卵巢肿瘤中也有表达。在体外，PGRMC1在促进正常卵巢细胞和卵巢癌细胞存活方面发挥着重要作用。鉴于调控卵巢癌生存的因素的临床意义，本文将重点介绍PGRMC1在卵巢癌中的作用，同时从健康卵巢和卵巢肿瘤细胞系中深入探讨PGRMC1的S作用机制。利用PGRMC1siRNA的研究表明，P4‘S在体外抑制卵巢细胞凋亡的能力依赖于PGRMC1。为了证实PGRMC1的重要性，我们评估了缺失PGRMC1的卵巢癌细胞系在完整裸鼠体内成瘤的能力。与表达PGRMC1的卵巢癌细胞相比，缺失PGRMC1的卵巢癌细胞在较少的小鼠中形成肿瘤(80%，而对照组为100%)。此外，来自PGRMC1缺失的卵巢癌细胞的肿瘤数量是对照组的50%。最后，由PGRMC1缺失的卵巢癌细胞形成的肿瘤大约是由PGRMC1正常水平的卵巢癌细胞形成的肿瘤的四分之一。PGRMC1缺失的肿瘤较小的原因之一是它们的微血管系统发育不良。目前尚不清楚PGRMC1是如何调节细胞存活和肿瘤生长的，但部分机制可能涉及对促进细胞存活和抑制细胞凋亡的基因的调节。
Various ovarian cell types including granulosa cells and ovarian surface epithelial cells express the progesterone (P4) binding protein, Progesterone Receptor Membrane Component-1 (PGRMC1). PGRMC1 is also expressed in ovarian tumors. PGRMC1 plays an essential role in promoting the survival of both normal and cancerous ovarian cell in vitro. Given the clinical significance of factors that regulate the viability of ovarian cancer, this review will focus on the role of PGRMC1 in ovarian cancer, while drawing insights into the mechanism of PGRMC1’s action from cell lines derived from healthy ovaries as well as ovarian tumors. Studies using PGRMC1 siRNA demonstrated that P4’s ability to inhibit ovarian cells from undergoing apoptosis in vitro is dependent on PGRMC1. To confirm the importance of PGRMC1, the ability of PGRMC1-deplete ovarian cancer cell lines to form tumors in intact nude mice was assessed. Compared to PGRMC1-expressing ovarian cancer cells, PGRMC1-deplete ovarian cancer cells formed tumors in fewer mice (80% compared to 100% for controls). Moreover, the number of tumors derived from PGRMC1-deplete ovarian cancer cells was 50% of that observed in controls. Finally, the tumors that formed from PGRMC1-deplete ovarian cancer cells were about a fourth the size of tumors derived from ovarian cancer cells with normal levels of PGRMC1. One reason for PGRMC1-deplete tumors being smaller is that they had a poorly developed microvasculature system. How PGRMC1 regulates cell viability and in turn tumor growth is not known but part of the mechanism likely involves the regulation of genes that promote cell survival and inhibit apoptosis.
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影响因子：
2.7
作者：
Peluso, John J.
通讯作者：
Peluso, John J.
影响因子：
4.3
作者：
Falkenstein, E;Eisen, C;Wehling, M
通讯作者：
Wehling, M
影响因子：
4.8
作者：
Kaipia, A;Hsu, SY;Hsueh, AJW
通讯作者：
Hsueh, AJW
DOI：
10.1046/j.1525-1438.1999.99075.x
发表时间：
1999-11-01
影响因子：
4.8
作者：
Halperin, R;Hadas, E;Schneider, D
通讯作者：
Schneider, D
黄体酮部分通过 PGRMC1 调节的基因表达抑制细胞凋亡。
影响因子：
4.1
作者：
Peluso JJ;Liu X;Gawkowska A;Lodde V;Wu CA
通讯作者：
Wu CA