Estrogens promote proliferation of the seminoma-like TCam-2 cell line through a GPER-dependent ERalpha36 induction.
Fiche publication
Date publication
mars 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FLAMENT Stéphane
Tous les auteurs :
Wallacides A, Chesnel A, Ajj H, Chillet M, Flament S, Dumond H
Lien Pubmed
Résumé
Seminoma, originated from carcinoma in situ cells (CIS), is one of the main causes of cancer in young men. Postpubertal development of these testicular germ cell tumors suggests a hormone-sensitive way of CIS cell proliferation induction. Using the unique seminoma TCam-2 cell line, we demonstrate that both estradiol and testosterone can stimulate TCam-2 cell proliferation in the absence of the estradiol receptor ERalpha. We establish that estradiol can activate GPER-cAMP/PKA signalling pathway. TCam-2 cells express ERalpha36, a truncated isoform of the canonical ERalpha receptor, the expression of which is rapidly induced after estrogen treatment in a GPER-dependent manner. ERalpha36 knockdown indicates that ERalpha36 is (i) a downstream target of E(2)-activated GPER/PKA/CREB pathway, (ii) required for estradiol-dependent EGFR expression, (iii) necessary for cell proliferation. Colocalization of ERalpha36 with cytoskeleton microfilaments suggests a role of estrogens in cell motility. Our results highlight the functional role of ERalpha36 in context of seminoma cell proliferation and the importance of testing ERalpha36 in vivo as a possible future prognostic marker.
Référence
Mol Cell Endocrinol. 2012 Mar 5;350(1):61-71