FSH stimulates ovarian cancer cell growth by action on growth factor variant receptor
FSH stimulates ovarian cancer cell growth by action on growth factor variant receptor
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DOI：
10.1016/j.mce.2006.11.010
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发表时间：
2007-03-15
影响因子：
4.1
通讯作者：
Freeman, L. C.
中科院分区：
文献类型：
--
作者：
Li, Y.;Ganta, S.;Freeman, L. C.
许多FSH受体（FSH- r）异构体具有不同的结构基元和信号范式，包括单一的跨膜结构域变体，其功能是作为生长因子型受体（FSH- r3）。本研究利用致瘤性小鼠卵巢表面上皮细胞（MOSEC）系ID8，验证了FSH通过作用于FSH- r3刺激卵巢癌细胞增殖的假设。FSH以浓度依赖性方式增强ID8增殖。此外，fsh处理ID8引发的细胞内事件与FSH-R3的激活一致，不同于与典型g蛋白偶联FSH-R亚型（FSH-R1）激活相关的事件。具体来说，FSH-R3信号通路包括SNX-482敏感成分Cav2.3钙通道下游的ERK的camp非依赖性激活。使用针对FSH-R外显子7和1 I的探针进行的Northern分析一致地只鉴定出一个1.9 kb的转录本。免疫印迹分析证实在ID8中FSH-R3表达，而fshr1未表达。总之，这些数据表明FSH-R3信号促进卵巢癌细胞的增殖。2007爱思唯尔爱尔兰有限公司版权所有。
A number of FSH receptor (FSH-R) isoforms with distinct structural motifs and signaling paradigms have been described, including a single transmembrane domain variant that functions as a growth factor type receptor (FSH-R3). This study tested the hypothesis that FSH can stimulate ovarian cancer cell proliferation by acting on FSH-R3, using the tumorigenic mouse ovarian surface epithelial cell (MOSEC) line ID8. FSH enhanced ID8 proliferation in a concentration-dependent fashion. Moreover, FSH-treatment of ID8 elicited intracellular events consistent with activation of FSH-R3 and distinct from those associated with activation of the canonical G-protein coupled FSH-R isoform (FSH-R1). Specifically, the FSH-R3 signaling pathway included CAMP-independent activation of ERK downstream of an SNX-482 sensitive component likely to be the Cav2.3 calcium channel. Northern analysis using probes specific for exons 7 and 1 I of FSH-R identified consistently only one 1.9 kb transcript. Immunoblot analysis confirmed expression of FSH-R3 but not FSHR-1 in ID8. Together, these data suggest that FSH-R3 signaling promotes proliferation of ovarian cancer cells. (c) 2007 Elsevier Ireland Ltd. All rights reserved.