title: High levels of GPR30 protein in human testicular carcinoma in situ and seminomas correlate with low levels of estrogen receptor-beta and indicate a switch in estrogen responsiveness.
abstract: The G protein-coupled estrogen receptor (GPR30) is suggested to be involved in non-nuclear estrogen signalling and is expressed in a variety of hormone dependent cancer entities. It is well established that oestrogens are involved in pathological germ cell proliferation including testicular germ cell tumours. This study was performed to further elucidate the role of this receptor and the possible correlation with the estrogen receptor β in human testicular carcinoma in situ (CIS), seminomas and in GC1 and TCam-2 germ cell lines; in addition, a Tissue Micro-Array was built using the most representative areas from 25 cases of human testicular seminomas and 20 cases of CIS. The expression of ERβ and GPR30 were observed by using Western blot analysis in combination with immunocytochemistry and immunofluorescence analyses. Here, we show that down regulation of ERβ associates with GPR30 over-expression both in human testicular CIS and seminomas. In addition, we show that 17β-oestradiol induces the ERK1/2 activation and increases c-Fos expression through GPR30 associated with ERβ down-regulation in TCam-2 cell line. The present results suggest that exposure to oestrogens or oestrogen-mimics, in some as of yet undefined manner, diminishes the ERβ-mediated growth restraint in CIS and in human testicular seminoma, probably due to ERβ down-regulation associated to GPR30 increased expression indicating that GPR30 could be a potential therapeutic target to design specific inhibitors.
authors.affiliation: Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università di Napoli "Federico II,", Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Boscia
authors.forename: Carmela
authors.initials: C
authors.lastname: Passaro
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Gigantino
authors.forename: Sisto
authors.initials: S
authors.lastname: Perdonà
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Portella
authors.forename: Sergio
authors.initials: S
authors.lastname: Chieffi
authors.forename: Paolo
authors.initials: P
authors.lastname: Chieffi
mesh_terms: D000328:Adult; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000031:analogs & derivatives / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018239:Seminoma / Q000378:metabolism*; D013736:Testicular Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D047629:Estrogen Receptor beta; D004967:Estrogens; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled