Defining molecular sensors to assess long-term effects of pesticides on carcinogenesis
| Autor: | Maud Marques, Fanny L'Héritier, Myriam Fauteux, Luc Gaudreau |
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| Rok vydání: | 2014 |
| Předmět: |
Male
aryl hydrocarbon receptor (AhR) Estrogen receptor Review Ligands lcsh:Chemistry chemistry.chemical_compound 0302 clinical medicine lcsh:QH301-705.5 Spectroscopy ERα Regulation of gene expression 0303 health sciences Cocarcinogenesis General Medicine 3. Good health Computer Science Applications Cell biology Crosstalk (biology) Cell Transformation Neoplastic Biochemistry 030220 oncology & carcinogenesis Female Signal Transduction Neoplasms Hormone-Dependent CYP1B1 Breast Neoplasms Biology Catalysis Xenobiotics Inorganic Chemistry 03 medical and health sciences Cytochrome P-450 CYP1A1 Humans Physical and Theoretical Chemistry Molecular Biology Transcription factor 030304 developmental biology Organic Chemistry Estrogen Receptor alpha Estrogens Receptor Cross-Talk pesticides Aryl hydrocarbon receptor Carcinogens Environmental Diet lcsh:Biology (General) lcsh:QD1-999 chemistry Gene Expression Regulation Receptors Aryl Hydrocarbon 13. Climate action biology.protein Xenobiotic Estrogen receptor alpha Biomarkers Genes Neoplasm |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 15, Iss 9, Pp 17148-17161 (2014) |
| ISSN: | 1422-0067 |
| Popis: | The abundance of dioxins and dioxin-like pollutants has massively increased in the environment due to human activity. These chemicals are particularly persistent and accumulate in the food chain, which raises major concerns regarding long-term exposure to human health. Most dioxin-like pollutants activate the aryl hydrocarbon receptor (AhR) transcription factor, which regulates xenobiotic metabolism enzymes that belong to the cytochrome P450 1A family (that includes CYP1A1 and CYP1B1). Importantly, a crosstalk exists between estrogen receptor α (ERα) and AhR. More specifically, ERα represses the expression of the CYP1A1 gene, which encodes an enzyme that converts 17β-estradiol into 2-hydroxyestradiol. However, (ERα) does not repress the CYP1B1 gene, which encodes an enzyme that converts 17β-estradiol into 4-hydroxyestradiol, one of the most genotoxic estrogen metabolites. In this review, we discuss how chronic exposure to xenobiotic chemicals, such as pesticides, might affect the expression of genes regulated by the AhR–ERα crosstalk. Here, we focus on recent advances in the understanding of molecular mechanisms that mediate this crosstalk repression, and particularly on how ERα represses the AhR target gene CYP1A1, and could subsequently promote breast cancer. Finally, we propose that genes implicated in this crosstalk could constitute important biomarkers to assess long-term effects of pesticides on human health. |
| Databáze: | OpenAIRE |
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