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Open AccessArticle

Genetic Variants of GPER/GPR30, a Novel Estrogen-Related G Protein Receptor, Are Associated with Human Seminoma

1
Institut National de la Santé et de la Recherche Médicale (INSERM) UMR U1065/UNS, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 5, Environnement, Reproduction et Cancers Hormono-Dépendants, Nice 06204, France
2
Institut Signalisation et Pathologie (IFR 50), Université de Nice-Sophia Antipolis, Faculté de Médecine, Nice 06000, France
3
Centre Hospitalier Universitaire de Nice, Hôpital de l'Archet, Service d'Endocrinologie, Diabétologie et Médecine de la Reproduction, Nice 06000, France
4
Foch, Laboratoire d'Anatomie Pathologique, Suresnes 92151, France
5
Laboratoire d'Anatomie et Cytologie Pathologiques, Centre Hospitalier Universitaire de Nice, Hôpital Pasteur, Nice 06000, France
6
Centre Hospitalier Universitaire de Nice, Hôpital de l'Archet, Service d'Urologie, Nice 06202, France
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2014, 15(1), 1574-1589; https://doi.org/10.3390/ijms15011574
Received: 25 November 2013 / Revised: 16 December 2013 / Accepted: 3 January 2014 / Published: 21 January 2014
(This article belongs to the Collection G Protein-Coupled Receptor Signaling and Regulation)
Testicular germ cell tumors (TGCTs) are the most common solid cancers in young men, with an increasing incidence over several years. However, their pathogenesis remains a matter of debate. Some epidemiological data suggest the involvement of both environmental and genetic factors. We reported two distinct effects of estrogens and/or xeno-estrogens on in vitro human seminoma-derived cells proliferation: (1) an antiproliferative effect via a classical estrogen receptor beta-dependent pathway, and (2) a promotive effect via a non-classical membrane G-protein-coupled receptor, GPR30/GPER, which is only overexpressed in seminomas, the most common TGCT. In order to explain this overexpression, we investigated the possible association of polymorphisms in the GPER gene by using allele-specific tetra-primer polymerase chain reaction performed on tissue samples from 150 paraffin-embedded TGCT specimens (131 seminomas, 19 non seminomas). Compared to control population, loss of homozygous ancestral genotype GG in two polymorphisms located in the promoter region of GPER (rs3808350 and rs3808351) was more frequent in seminomas but not in non-seminomas (respectively, OR = 1.960 (1.172–3.277) and 7.000 (2.747–17.840); p < 0.01). These polymorphisms may explain GPER overexpression and represent a genetic factor of susceptibility supporting the contribution of environmental GPER ligands in testicular carcinogenesis. View Full-Text
Keywords: GPER; GPR30; JKT-1 cells; estrogens; xeno-estrogens; testicular cancer; seminoma; polymorphisms; SNP; genetic susceptibility GPER; GPR30; JKT-1 cells; estrogens; xeno-estrogens; testicular cancer; seminoma; polymorphisms; SNP; genetic susceptibility
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MDPI and ACS Style

Chevalier, N.; Paul-Bellon, R.; Camparo, P.; Michiels, J.-F.; Chevallier, D.; Fénichel, P. Genetic Variants of GPER/GPR30, a Novel Estrogen-Related G Protein Receptor, Are Associated with Human Seminoma. Int. J. Mol. Sci. 2014, 15, 1574-1589.

AMA Style

Chevalier N, Paul-Bellon R, Camparo P, Michiels J-F, Chevallier D, Fénichel P. Genetic Variants of GPER/GPR30, a Novel Estrogen-Related G Protein Receptor, Are Associated with Human Seminoma. International Journal of Molecular Sciences. 2014; 15(1):1574-1589.

Chicago/Turabian Style

Chevalier, Nicolas; Paul-Bellon, Rachel; Camparo, Philippe; Michiels, Jean-François; Chevallier, Daniel; Fénichel, Patrick. 2014. "Genetic Variants of GPER/GPR30, a Novel Estrogen-Related G Protein Receptor, Are Associated with Human Seminoma" Int. J. Mol. Sci. 15, no. 1: 1574-1589.

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