Bisphenol A disrupts seminoma cell proliferation following an inverted U-shaped non monotonic dose-response curve, due to its greater affinity for GPR30, the non classical membrane G protein-related estrogen receptor, than for ER[beta]

Testicular germ cell tumours are the most frequent cancer of young men between 15 and 35 years of age. While pathogenesis and reasons of an increasing incidence (about 2% each year) all over the world remain unknown, 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, EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. Using a human seminoma cell line (JKT-1), which expressed ER beta but not ER alpha, we previously reported that bisphenol A (BPA) could induce cell proliferation at a very low concentration (10-9M) independently of the classical estrogen receptor ER beta (Bouskine et al., Endocrinology, 2008). The non classical membrane G-protein coupled estrogen receptor (GPER or GPR30) has been recently shown to mediate the effects of several xenoestrogens through rapid non genomic act ivat ion of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium).