GPR30, the non-classical membrane G protein related estrogen receptor, is overexpressed in human seminoma and promotes seminoma cell proliferation.
GPR30, the non-classical membrane G protein related estrogen receptor, is overexpressed in human seminoma and promotes seminoma cell proliferation.
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DOI：
10.1371/journal.pone.0034672
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fénichel P
中科院分区：
文献类型：
--
作者：
Chevalier N;Vega A;Bouskine A;Siddeek B;Michiels JF;Chevallier D;Fénichel P
睾丸生殖细胞肿瘤是年轻男性最常见的癌症，在世界各地的发病率不断上升。发病机制和原因尚不清楚，但流行病学和临床数据表明，胎儿暴露于具有雌激素效应的环境内分泌干扰物（EEDs）可能参与睾丸生殖细胞癌变。然而，这些EED（如双酚A）通常是经典核雌激素受体的弱配体。最近几个研究小组表明，非经典的膜G蛋白偶联雌激素受体（GPER/GPR 30）介导的雌激素和几种外源性雌激素的作用，通过快速非基因组激活的信号转导途径在各种人类雌激素依赖性癌细胞（乳腺癌，卵巢癌，子宫内膜癌）。本研究的目的是证明GPER在睾丸肿瘤中过表达，并能够触发JKT-1肿瘤细胞增殖。我们在这里报告的第一次完整的形态和功能的GPER在正常和恶性人类睾丸生殖细胞的特点。在正常成年人睾丸中，GPER由体细胞（支持细胞）和生殖细胞（精原细胞和精母细胞）表达。GPER仅在腺瘤中过表达，这是最常见的睾丸生殖细胞癌，定位于细胞膜并在体外触发对JKT-1细胞的增殖作用，其被G15（GPER选择性拮抗剂）和siRNA失效完全消除。这些结果表明，GPER由人类正常成年睾丸生殖细胞表达，在卵巢癌肿瘤中特异性过表达，并且能够在体外触发卵巢癌细胞增殖。因此，在睾丸生殖细胞癌中评估异种雌激素或其他内分泌干扰物时，应考虑其而不是经典ER。它也可能代表一个预后标志物和/或肿瘤的治疗靶点。
Testicular germ cell tumours are the most frequent cancer of young men with an increasing incidence all over the world. Pathogenesis and reasons of this increase remain unknown but epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs) with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, these EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. Several research groups recently showed that the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30) mediates the effects of estrogens and several xenoestrogens through rapid non genomic activation of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium). The aim of this study was to demonstrate that GPER was overexpressed in testicular tumours and was able to trigger JKT-1 seminoma cell proliferation. We report here for the first time a complete morphological and functional characterization of GPER in normal and malignant human testicular germ cells. In normal adult human testes, GPER was expressed by somatic (Sertoli cells) and germ cells (spermatogonia and spermatocytes). GPER was exclusively overexpressed in seminomas, the most frequent testicular germ cell cancer, localized at the cell membrane and triggered a proliferative effect on JKT-1 cells in vitro, which was completely abolished by G15 (a GPER selective antagonist) and by siRNA invalidation. These results demonstrate that GPER is expressed by human normal adult testicular germ cells, specifically overexpressed in seminoma tumours and able to trigger seminoma cell proliferation in vitro. It should therefore be considered rather than classical ERs when xeno-estrogens or other endocrine disruptors are assessed in testicular germ cell cancers. It may also represent a prognosis marker and/or a therapeutic target for seminomas.
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影响因子：
3.6
作者：
Bourdon, V;Lablack, A;Pointis, G
通讯作者：
Pointis, G
影响因子：
3.6
作者：
Franco, Renato;Boscia, Francesca;Chieffi, Paolo
通讯作者：
Chieffi, Paolo
DOI：
10.1016/s0960-0760(01)00190-x
发表时间：
2002-02-01
影响因子：
4.1
作者：
Filardo, EJ
通讯作者：
Filardo, EJ
影响因子：
--
作者：
Filardo, EJ;Quinn, JA;Bland, KI
通讯作者：
Bland, KI
影响因子：
4.8
作者：
Chang, Edmund C.;Frasor, Jonna;Katzenellenbogen, Benita S.
通讯作者：
Katzenellenbogen, Benita S.