Impact d'une surexpression d'ERα36 et/ou d'une exposition aux alkylphénols sur la physiopathologie de la glande mammaire

Abstract : This work was dedicated to study how a variant of estrogen receptor α, ERα36, acts in initiation and progression of breast cancer. In the laboratory, his expression in testicular cancer was shown to stimulate cell proliferation in vitro and in vivo after environmental pollutant exposure. The compounds studied, the alkylphenols, are endocrine disruptors, interfering with normal estrogen signaling. Gene interaction network modelling from retrospective analysis of breast cancer samples showed that ERα36 expression was correlated with the expression of cell migration markers, typical of tumor progression. In vitro ERα36 overexpression and in a unique mouse Knocked In model, expressing ERα36 in the mammary gland, showed that ERα36 is sufficient to alter epithelial phenotype of normal breast cells. Alkylphenols exposure, that stimulated ERα36 endogenous expression, increased cellular alterations and contributed to transgenerational acquisition of properties related to neoplastic transformation. Analysis of this multidisciplinary project were based on biological expertise, mathematics and bioinformatic tools. These results enabled to highlight for the first time the potential role of ERα36 in tumor initiation and confirmed his involvement in breast cancer progression. Finally, we showed that exposure to environmental doses of alkylphenols during the perinatal period can lead to transgenerational modification of mammary gland differentiation under ERα36control and eventually may increase breast cancer risk.
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  • HAL Id : tel-01673798, version 2


Clémence Chamard-Jovenin. Impact d'une surexpression d'ERα36 et/ou d'une exposition aux alkylphénols sur la physiopathologie de la glande mammaire. Cancer. Université de Lorraine, 2016. Français. ⟨NNT : 2016LORR0232⟩. ⟨tel-01673798v2⟩



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