title: Estrogen-induced growth inhibition of human seminoma cells expressing estrogen receptor beta and aromatase.
abstract: It is now 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. Studying a human testicular seminoma cell line, JKT-1, we show here that 17beta-estradiol (10(-12) to 10(-6) M) induced in vitro a significant dose-dependent decrease of cell growth. This antiproliferative effect was maximum after 4 days of exposure at a physiologically intratesticular concentration of 10(-9) M, close to the K(d) of ER, and reversed by ICI 182780, an ER antagonist, suggesting an ER-mediated pathway. By RT-PCR and Western blot we were able to confirm that JKT-1, like tumoral seminoma cells and normal human testicular basal germ cells, expresses estrogen receptor beta (ERbeta), including ERbeta1 and ERbeta2, a dominant negative variant, but not ERalpha. Using immunofluorescence and confocal microscopy, ERbeta was observed as perinuclear intracytoplasmic spots in JKT-1 and tumoral seminoma cells without significant translocation of ERbeta into the nucleus, under 17beta-estradiol exposure. Double staining observed by confocal microscopy revealed that ERbeta colocalized in JKT-1 cells with cytochrome C, a mitochondrial marker. We report for the first time the expression of a functional aromatase complex in seminoma cells as assessed by RT-PCR, Western blot and enzymatic assay. Seminoma cells are able to respond to estrogens through a possible autocrine or paracrine loop. These preliminary results support estrogen-dependency of human testicular seminoma, the most frequent tumor of young men, and suggest potential pharmacological use. Whether this estrogen control, however, involves an ERbeta-mediated stimulation of cell apoptosis and/or an ERbeta-mediated inhibition of cell proliferation, remains to be further determined.
authors.affiliation: INSERM U 670, 28 avenue de Valombrose, Faculté de Médecine, 06102 Nice Cedex 2, France.
authors.forename: C
authors.initials: C
authors.lastname: Roger
authors.forename: S
authors.initials: S
authors.lastname: Lambard
authors.forename: A
authors.initials: A
authors.lastname: Bouskine
authors.forename: B
authors.initials: B
authors.lastname: Mograbi
authors.forename: D
authors.initials: D
authors.lastname: Chevallier
authors.forename: M
authors.initials: M
authors.lastname: Nebout
authors.forename: G
authors.initials: G
authors.lastname: Pointis
authors.forename: S
authors.initials: S
authors.lastname: Carreau
authors.forename: P
authors.initials: P
authors.lastname: Fenichel
mesh_terms: D001141:Aromatase / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism*; D000077267:Fulvestrant; D015870:Gene Expression; D006801:Humans; D008297:Male; D018239:Seminoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; D020847:Estrogen Receptor Modulators; D047629:Estrogen Receptor beta; D000077267:Fulvestrant; D004958:Estradiol; D001141:Aromatase