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Influence des micropolluants en mélange sur la croissance de tumeurs testiculaires d'origine germinale

Abstract : In vitro and in vivo epidemiological studies showed that the exposure of men to endocrine disruptors triggers the initiation and the progression of the testis cancer (Beiki et al., 2010). The fetal exposure to these products is able to alter the differentiation of germ cells in the timing of their development during the fetal life. The aim of our study was to determine the role of an endocrine disruptor mix on the proliferation of seminoma cells TCam-2. We also identified the pathways involved. In this study, we focused on the estrogen-like effects of an alkylphenol mixture called M4 (4-tert-octylphenol and 4-nonylphenol): in vitro we measured the proliferation of TCam-2 seminoma cells after M4 exposure and in vivo, we measured the tumor growth of NT2/D1 cells xenografted into Nude mice. The results highlighted the implication of ER[alpha]36 receptor, a truncated isoform of ER[alpha], in the response to the alkylphenol mixture M4. This mixture stimulates the cell proliferation of testicular cancer cells and the expression of the ER[alpha]36 receptor. These effects are mediated by CREB phosphorylation via the PI3K-ER[alpha]36-dependant pathway, and end by downregulation of Dnmt3 genes, thus limiting the level of DNA methylation. Therefore ER[alpha]36 appears to be a promising therapeutic target for testis cancer treatment
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Hussein Ajj. Influence des micropolluants en mélange sur la croissance de tumeurs testiculaires d'origine germinale. Médecine humaine et pathologie. Université de Lorraine, 2014. Français. ⟨NNT : 2014LORR0215⟩. ⟨tel-01751194⟩



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