In vitro and in vivo epidemiological studies have shown that the exposure of men to endocrine disruptors triggers the initiation and the progression of testis cancer. The fetal exposure to these products is able to alter the differentiation of germ cells during their development. 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-tertoctylphenol 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 ERα36, a truncated isoform of the estrogen receptor ERα, in the response to the alkylphenol mixture M4. This mixture stimulates the proliferation of testicular cancer cells and the expression of the ERα36 receptor. These effects are mediated by CREB phosphorylation via the PI3K-ERα36-dependant pathway, and end by down-regulation of Dnmt3 genes, encoding DNA methyl transferases, thus limiting the level of DNA methylation. Therefore ERα36 appears to be a promising therapeutic target for testis cancer treatment.
from HAL : Dernières publications http://ift.tt/1HZQke1
from HAL : Dernières publications http://ift.tt/1HZQke1
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