Identification of the estrogen receptor GPER in neoplastic and non-neoplastic human testes
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RESEARCH
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Identification of the estrogen receptor GPER in neoplastic and non-neoplastic human testes Vittoria Rago1, Francesco Romeo2, Francesca Giordano1, Marcello Maggiolini3 and Amalia Carpino1*
Abstract Background: Estrogen signaling is mediated by estrogen receptor beta isoforms in normal and neoplastic human testes. Recently, a G-protein-coupled-receptor (GPER) has been suggested as being involved in rapid responses to estrogens in different normal and tumor cells. Methods: This study investigated the GPER expression in paraffin-embedded samples from non neoplastic and neoplastic human testes (sex-cord stromal and germ cell tumors) by immunohistochemical and Western Blot analyses. Results: In control testes, a positive GPER immunoreactivity was detected in Leydig and in Sertoli cells while all germ cells were immunonegative. Furthermore, neoplastic cells of the Sertoli cell tumor, Leydig cell tumor, seminoma and embryonal carcinoma samples were all immunopositive. The immunoblots of testis extracts confirmed the results. Conclusions: These findings suggest that GPER could mediate estrogen signaling in both normal and transformed somatic cells of human testis, but they reveal a differential expression of the novel estrogen receptor in non neoplastic and neoplastic germ cells.
Background Estrogens exert their pleiotropic and tissue-specific effects on target cells through the differential expression of the classical estrogen receptors (ERs), ERa and ERb, which mediate both genomic and rapid signaling events [1,2]. In addition, estrogens induce rapid non-genomic responses from membrane-associated receptors such as growth factor receptors and G protein-coupled receptors [3]. In the last years, a member of the 7-transmembrane G protein-coupled receptor family, GPR30, has been identified as a candidate to promote estrogen action in target cells [4-6] and different investigations have reported the expression of this novel estrogen receptor in a large variety of cell types [7]. Furthermore, GPR30 has been shown to have estrogen-binding affinity and to mediate estrogen-signal transduction events like calcium mobilization, kinase activation [5] and rapid transcriptional activation of early genes [8]. Therefore, despite some controversies regarding its biological role [9], GPR30 is now widely recognized as an estrogen receptor,
with the new acronym G-protein coupled estrogen receptor GPER, by the International Union of Basic and Clinical Pharmacology [10] In the human, GPER (GPR30) has been detected n heart, lung, liver, intestine, ovary, prostate, kidney, brain [11]. In addition, GPER (GPR30)has been also evidenced in neoplastic tissues from breast, endometrial and ovary cancers [12-14] as well as in breast [15-17], endometrial [18,19] ovarian [20] and thyroid carcinoma cells lines [21]. However, the association of the novel estrogen receptor with human cancer has only recently begun to be defined. A large body of data indicated that estrogens regulate testis physiology [1] and they are also involved in
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