Background: Testicular germ cell tumours are the most frequent cancer of young men. While pathogenesis and reasons of an increasing incidence all over the world remain unknown, epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs), especially with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. In fact, this promoting effect could act through the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30), which has been recently shown to mediate the effects of several xenoestrogens and also overexpressed in various estrogen dependent cancer cells (breast, ovary, endometrium).
Methods: The aim of this study was to demonstrate that GPER was also overexpressed in testicular tumours (n=15) compared to normal peritumoral testicular tissue and was able to trigger JKT-1 seminoma cell proliferation in vitro.
Results: In normal adult human testes, GPER was expressed by somatic (Sertoli cells) and germ cells (spermatogonia and spermatocytes). GPER was exclusively and significantly (P < 0.05) overexpressed in seminomas, the most frequent testicular germ cell cancer. In JKT-1 seminoma cells, GPER was localized at the cell membrane and triggered in vitro the proliferative effect induced by G1 (a GPER selective agonist) and by an impermeable E2-conjugate (E2-BSA). This effect was completely abolished by G15 (a GPER selective antagonist) and by GPER siRNA invalidation.
Conclusion: Our results confirm that human seminomas overexpressed functional GPER; moreover, agonist and antagonists demonstrate its ability to induce proliferative effect in seminoma cells. Thus, this non classical membrane G protein related estrogen receptor may represent a molecular basis for a possible effect of xenoestrogens during testicular carcinogenesis.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.
05 - 09 May 2012
European Society of Endocrinology