GPR30, the Non-Classical Membrane G Protein Related Estrogen Receptor, Is Overexpressed in Human Seminoma and Promotes Seminoma Cell Proliferation
نویسندگان
چکیده
BACKGROUND 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. RESULTS 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. CONCLUSION 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.
منابع مشابه
Genetic Variants of GPER/GPR30, a Novel Estrogen-Related G Protein Receptor, Are Associated with Human Seminoma
Testicular germ cell tumors (TGCTs) are the most common solid cancers in young men, with an increasing incidence over several years. However, their pathogenesis remains a matter of debate. Some epidemiological data suggest the involvement of both environmental and genetic factors. We reported two distinct effects of estrogens and/or xeno-estrogens on in vitro human seminoma-derived cells prolif...
متن کاملComment on “Effects of Atrazine on Estrogen Receptor α– and G Protein–Coupled Receptor 30–Mediated Signaling and Proliferation in Cancer Cells and Cancer-Associated Fibroblasts”
Albanito et al. recently reported that the herbicide atrazine was able to exert an estrogen-like proliferative activity in various cell models, including ovarian and breast cancer cells and cancer-associated fibroblasts, by inducing the expression of several estrogen target genes without binding to or activating the classical estrogen receptor (ER) α. They also showed that G protein–coupled rec...
متن کاملResponse to “Comment on ‘Effects of Atrazine on Estrogen Receptor α– and G Protein–Coupled Receptor 30–Mediated Signaling and Proliferation in Cancer Cells and Cancer-Associated Fibroblasts’”
Albanito et al. recently reported that the herbicide atrazine was able to exert an estrogen-like proliferative activity in various cell models, including ovarian and breast cancer cells and cancer-associated fibroblasts, by inducing the expression of several estrogen target genes without binding to or activating the classical estrogen receptor (ER) α. They also showed that G protein–coupled rec...
متن کاملLow Concentrations of Bisphenol A Induce Mouse Spermatogonial Cell Proliferation by G Protein–Coupled Receptor 30 and Estrogen Receptor-α
BACKGROUND Bisphenol A (BPA) is one of the most prevalent chemicals in daily-use materials; therefore, human exposure to BPA is ubiquitous. The estrogenicity of BPA is generally mediated by nuclear estrogen receptors (ERs). However, low concentrations of BPA stimulate seminoma cell proliferation by an uncertain mechanism that does not involve activation of ERs. OBJECTIVE We investigated the p...
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