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Down‐regulation of oestrogen receptor‐β associates with transcriptional co‐regulator PATZ1 delocalization in human testicular seminomas
Author(s) -
Esposito Francesco,
Boscia Francesca,
Franco Renato,
Tornincasa Mara,
Fusco Alfredo,
Kitazawa Sohei,
Looijenga Leendert H,
Chieffi Paolo
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2846
Subject(s) - biology , germ cell , transcriptional regulation , microbiology and biotechnology , cytoplasm , regulator , testicular germ cell tumor , nuclear receptor , zinc finger , seminoma , medicine , endocrinology , cancer research , transcription factor , genetics , gene , chemotherapy
Abstract Oestrogen exposure has been linked to a risk for the development of testicular germ cell cancers. The effects of oestrogen are now known to be mediated by oestrogen 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 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 mislocalization could be associated with the development of testicular germ cell tumours. Here we show that ER β interacts with PATZ1 in normal germ cells, while down‐regulation of ER β associates with transcriptional co‐regulator PATZ1 delocalization in human testicular seminomas. In addition, we show that the translocation of PATZ1 from the cytoplasm into the nucleus is regulated by cAMP, which also induces increased expression and nuclear localization of ERβ, while this effect is counteracted by using the anti‐oestrogen ICI 182‐780. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.