title: Defining molecular sensors to assess long-term effects of pesticides on carcinogenesis.
abstract: 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.
authors.affiliation: Département de Biologie, Université de Sherbrooke, 2500 boul. de l'Université, Sherbrooke, QC J1K 2R1, Canada. Fanny.Lheritier@USherbrooke.ca.
authors.forename: Fanny
authors.initials: F
authors.lastname: L'Héritier
authors.affiliation: Département de Biologie, Université de Sherbrooke, 2500 boul. de l'Université, Sherbrooke, QC J1K 2R1, Canada. Maud.Marques@USherbrooke.ca.
authors.forename: Maud
authors.initials: M
authors.lastname: Marques
authors.affiliation: Département de Biologie, Université de Sherbrooke, 2500 boul. de l'Université, Sherbrooke, QC J1K 2R1, Canada. Myriam.Fauteux@USherbrooke.ca.
authors.forename: Myriam
authors.initials: M
authors.lastname: Fauteux
authors.affiliation: Département de Biologie, Université de Sherbrooke, 2500 boul. de l'Université, Sherbrooke, QC J1K 2R1, Canada. Luc.Gaudreau@Usherbrooke.ca.
authors.forename: Luc
authors.initials: L
authors.lastname: Gaudreau
mesh_terms: D015415:Biomarkers; D001943:Breast Neoplasms / Q000209:etiology; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003043:Cocarcinogenesis; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D004032:Diet; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000502:physiology; D004967:Estrogens; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D052138:Genes, Neoplasm / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000209:etiology; D010575:Pesticides / Q000633:toxicity*; D020239:Receptor Cross-Talk / Q000187:drug effects; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D015262:Xenobiotics / Q000633:toxicity
chemical_list: D015415:Biomarkers; D002274:Carcinogens, Environmental; D047628:Estrogen Receptor alpha; D004967:Estrogens; D008024:Ligands; D010575:Pesticides; D018336:Receptors, Aryl Hydrocarbon; D015262:Xenobiotics; D019363:Cytochrome P-450 CYP1A1