Down-regulation of estrogen receptor-β associates with transcriptional coregulator PATZ1 delocalization in human testicular seminomas
Francesco Esposito1, Renato Franco2, Monica Fedele1, Alfredo Fusco1, Paolo Chieffi1,3 & Francesca Bosica1
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, and associates with a variety of transcription factors (i.e. RNF4, HMGA1, gscl, SPBP). We have previously described, by using mice lacking the PATZ1 gene, its crucial role in spermatogenesis. Consistently, PATZ1-KO mice are unfertile and testes from these mice showed only few spermatocytes, associated with increased apoptosis, and complete absence of spermatids and spermatozoa. In addition, PATZ1 protein is expressed, among germ cells, in spermatogonia, and in Sertoli cells.
Preliminary results indicate that PATZ1 interacts with estrogen receptor beta (ERβ). Since PATZ1 has been indicated as a potential tumour suppressor gene, we also looked at its expression in tumours deriving from testicular germ cells (TGCTs). Although expression of PATZ1 protein was increased in these tumours, it was delocalized in the cytoplasm, suggesting an impaired function. In addition, in seminomas the PATZ1 cytoplasmic localization is associated with ERβ down regulation.
These results indicate that PATZ1 plays a crucial role in normal male gametogenesis and that its up-regulation and mis-localization, associated with ERβ down-regulation, could have a crucial role in the development of seminomas.