Abstract
BackgroundTesticular 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.ResultsWe 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.ConclusionThese 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.
Highlights
Testicular germ cell cancer is the most frequent cancer occurring in young men and originates from transformed gonocytes or undifferentiated spermatogonia [1], which respectively derived from foetal germ cells and adult germ stem cells
G protein-coupled oestrogen receptor (GPER) immunolocalization in normal and tumoural testes Human testicular tissues were studied by immunofluorescence to determine whether GPER was expressed in normal testis and seminomas
The colocalization of GPER and E2 coupled to BSA (E2-BSA) at the JKT-1 cell membrane supported the notion that GPER could bind E2-BSA and could be a good candidate to mediate its proliferative effect previously reported in these cells [8]
Summary
Testicular germ cell cancer is the most frequent cancer occurring in young men and originates from transformed gonocytes or undifferentiated spermatogonia [1], which respectively derived from foetal germ cells and adult germ stem cells. The physiological role of oestrogens during spermatogenesis and the molecular mechanisms by which they regulate germ cell proliferation remain to be elucidated Identifying these mechanisms is important because foetal exposure to environmental oestrogens is held responsible for the increasing incidence of male infertility and testicular cancer [1,4], which stem from impaired and excessive germ cell proliferation, respectively. 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. These EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
