title: The high-mobility group A1-estrogen receptor β nuclear interaction is impaired in human testicular seminomas.
abstract: It is well established that estrogens participate in the control of normal spermatogenesis and endogenous or environmental estrogens are involved in pathological germ cell proliferation including testicular germ cell tumors. 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 human testicular seminomas. The expression and the possible interaction of ERβ and HMGA1 were studied in normal germ cells and in human testicular seminomas. GC1 and TCam-2 germ cell lines, were used; in addition, a tissue micro-array (TMA) was built using the most representative areas from 35 cases of human testicular seminomas. The expression and the interaction of ERβ and HMGA1 were observed by using immunoprecipitation and Western blot analyses in combination with immunocytochemistry and immunofluorescence analyses. Here, we show that ERβ interacts with HMGA1 in normal germ cells, while down regulation of ERβ associates with transcriptional co-regulator HMGA1 over-expression and cytoplasmic localization both in human testicular seminomas and in TCam-2 cell line. In addition, we show that 17β-oestradiol induces an HMGA1 increased cytoplasmic expression associated to an ERβ down-regulation in TCam-2 cell line. Taken together, our results suggest that exposure to estrogens or estrogen-mimics, in some as of yet undefined manner, diminishes the ERβ-mediated growth restraint in human testicular seminoma, probably due to the HMGA1 cytoplasmic delocalization associated with ERβ down-regulation.
authors.affiliation: Dipartimento di Medicina Sperimentale, II Università di Napoli, Via Costantinopoli, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Esposito
authors.forename: Francesca
authors.initials: F
authors.lastname: Boscia
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Gigantino
authors.forename: Mara
authors.initials: M
authors.lastname: Tornincasa
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.forename: Paolo
authors.initials: P
authors.lastname: Chieffi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D025741:HMGA1a Protein / Q000235:genetics / Q000378:metabolism*; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D040081:Protein Array Analysis; D011485:Protein Binding; D018239:Seminoma / Q000378:metabolism*; D013736:Testicular Neoplasms / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D025743:HMGA2 Protein; D025741:HMGA1a Protein; D004958:Estradiol