title: Estrogens promote proliferation of the seminoma-like TCam-2 cell line through a GPER-dependent ERα36 induction.
abstract: 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 ERα. We establish that estradiol can activate GPER-cAMP/PKA signalling pathway. TCam-2 cells express ERα36, a truncated isoform of the canonical ERα receptor, the expression of which is rapidly induced after estrogen treatment in a GPER-dependent manner. ERα36 knockdown indicates that ERα36 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 ERα36 with cytoskeleton microfilaments suggests a role of estrogens in cell motility. Our results highlight the functional role of ERα36 in context of seminoma cell proliferation and the importance of testing ERα36 in vivo as a possible future prognostic marker.
authors.affiliation: EA4421, Signalisation, Génomique et Recherche Translationnelle en Oncologie, Nancy-Université, Nancy, France.
authors.forename: Angelina
authors.initials: A
authors.lastname: Wallacides
authors.forename: Amand
authors.initials: A
authors.lastname: Chesnel
authors.forename: Hussein
authors.initials: H
authors.lastname: Ajj
authors.forename: Martine
authors.initials: M
authors.lastname: Chillet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Flament
authors.forename: Héène
authors.initials: H
authors.lastname: Dumond
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D018239:Seminoma; D015398:Signal Transduction; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; C109584:GPER1 protein, human; D020033:Protein Isoforms; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D019938:Cyclin D1; D013739:Testosterone; D004958:Estradiol; D000242:Cyclic AMP; D066246:ErbB Receptors; D017868:Cyclic AMP-Dependent Protein Kinases