Estrogen exposure has been linked to a risk for the development of testicular germ cell cancers. The effects of estrogen are now known to be mediated by estrogen receptor α (ERα) and ERβ subtypes, but only ERβ has been found in human germ cells of normal testis. However, its expression was markedly diminished in seminomas, embryonal cell carcinomas, and in mixed germ cell tumours but remains high in teratomas. PATZ1 is a recently discovered zinc finger protein that, due to the presence of the POZ domain, acts as a transcriptional repressor affecting the basal activity of different promoters. We have previously described that PATZ1 plays a crucial role in normal male gametogenesis and that its up-regulation and mis-localization could be associated to the development of testicular germ cell tumours. Here, we show that ERβ interacts with PATZ1, and PKA (regulatory subunit) in normal germ cells, while down regulation of ERβ associates with transcriptional coregulator PATZ1 delocalization in human testicular seminomas. Interestingly, we found that the translocation of PATZ1 from the cytoplasm into the nucleus is regulated by cAMP that induces also an ERβ increased expression and nuclear localization, while this effect is counteracted by using the anti-estrogen ICI 182-780.
Taken together, our results demonstrate for the first time the interaction between PATZ1 and ERβ in normal germ cells; consistently, the PATZ1 delocalization associated with ERβ down regulation in human testicular seminomas, could be ascribed to an impaired cAMP mediated signalling to generate the testicular neoplasia.
30 Apr - 04 May 2011
European Society of Endocrinology