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INSERM U 670, 28 avenue de Valombrose, Faculté de Médecine, 06102 Nice Cedex 2, France
1 UPRES EA 2608-USC INRA, Université-IBFA, Caen 14032, France
(Requests for offprints should be addressed to P Fenichel; Email: Fenichel{at}unice.fr)
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 17ß-estradiol (1012 to 106 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 109 M, close to the Kd 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 ß (ERß), including ERß1 and ERß2, a dominant negative variant, but not ER
. Using immunofluorescence and confocal microscopy, ERß was observed as perinuclear intracytoplasmic spots in JKT-1 and tumoral seminoma cells without significant translocation of ERß into the nucleus, under 17ß-estradiol exposure. Double staining observed by confocal microscopy revealed that ERß 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 ERß-mediated stimulation of cell apoptosis and/or an ERß-mediated inhibition of cell proliferation, remains to be further determined.
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