Session: FP38-Physiological Impacts of Endocrine Disrupting Chemicals
Room 256 (Moscone Center)
Poster Board MON-343
Using a human seminoma cell line (JKT-1), we previously reported that bisphenol A could induce cell proliferation at a very low concentration (10-9M) independently of the classical estrogen receptor ERβ. As the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30) has been recently shown to mediate the effects of several xenoestrogens through rapid non genomic activation of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium), we supposed that bisphenol A could act through GPR30 in seminoma cells.
Methods: The aim of this study was to demonstrate that GPER was overexpressed in testicular tumours (n = 15) compared to normal peritumoral testicular tissue and was able to trigger seminoma cell proliferation induced by bisphenol A in vitro, using selective antagonist of GPR30/GPER and siRNA invalidation.
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, but not in non seminomas, compared to normal testicular tissue of each patient.
In JKT-1 seminoma cells, bisphenol A, like E2-BSA, a non-permeable estrogenic conjugate, induced a proliferative effect in vitro, with a non-monotonic dose response curve. This effect was completely abolished by G15 (a GPR30/GPER selective antagonist) and by siRNA invalidation.
Conclusion: Our results confirm that human seminomas overexpressed functional GPR30/GPER. As it triggered the E2-BSA and bisphenol A induced proliferative effects in seminoma cells, GPR30/GPER represents a molecular basis for a possible promotive effect of xenoestrogens like bisphenol A during testicular carcinogenesis. This hypothesis is actually under verification in our lab.
Nothing to Disclose: NC, RP, AV, AB, PF
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