AhR ligands reactivate LINE-1 retrotransposon in triple-negative breast cancer cells MDA-MB-231 and non-tumorigenic mammary epithelial cells NMuMG
| Autor: | C. Daniel Zappia, Ayelen L. Gomez, Federico Monczor, Lorena Vanesa Zárate, Noelia Miret, Marianela Lasagna, Laura Kass, Andrea Randi, Gabriela A. Altamirano, Carolina Pontillo, Claudia Cocca |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CIENCIAS MÉDICAS Y DE LA SALUD Retroelements Ciencias de la Salud Triple Negative Breast Neoplasms ARYL HYDROCARBON RECEPTOR SMAD Ligands medicine.disease_cause Biochemistry 03 medical and health sciences purl.org/becyt/ford/3.3 [https] 0302 clinical medicine BREAST CANCER Cell Line Tumor Basic Helix-Loop-Helix Transcription Factors Hexachlorobenzene medicine Humans Epigenetics Triple-negative breast cancer Pharmacology Dose-Response Relationship Drug biology Chemistry Cell growth Epithelial Cells Environmental exposure Aryl hydrocarbon receptor LONG INTERSPERSED NUCLEAR ELEMENT-1 CHLORPYRIFOS Otras Ciencias de la Salud Long Interspersed Nucleotide Elements 030104 developmental biology Receptors Aryl Hydrocarbon HEXACHLOROBENZENE 030220 oncology & carcinogenesis DNA methylation biology.protein Cancer research Female purl.org/becyt/ford/3 [https] Carcinogenesis |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| Popis: | Breast cancer is the most common cancer type in females worldwide. Environmental exposure to pesticides affecting hormonal homeostasis does not necessarily induce DNA mutations but may influence gene expression by disturbances in epigenetic regulation. Expression of long interspersed nuclear element-1 (LINE-1) has been associated with tumorigenesis in several cancers. In nearly all somatic cells, LINE-1 is silenced by DNA methylation in the 5́′UTR and reactivated during disease initiation and/or progression. Strong ligands of aryl hydrocarbon receptor (AhR) activate LINE-1 through the transforming growth factor-β1 (TGF-β1)/Smad pathway. Hexachlorobenzene (HCB) and chlorpyrifos (CPF), both weak AhR ligands, promote cell proliferation and migration in breast cancer cells, as well as tumor growth in rat models. In this context, our aim was to examine the effect of these pesticides on LINE-1 expression and ORF1p localization in the triple-negative breast cancer cell line MDA-MB-231 and the non-tumorigenic epithelial breast cell line NMuMG, and to evaluate the role of TGF-β1 and AhR pathways. Results show that 0.5 μM CPF and 0.005 μM HCB increased LINE-1 mRNA expression through Smad and AhR signaling in MDA-MB-231. In addition, the methylation of the first sites in 5́′UTR of LINE-1 was reduced by pesticide exposure, although the farther sites remained unaffected. Pesticides modulated ORF1p localization in MDA-MB-231: 0.005 μM HCB and 50 μM CPF increased nuclear translocation, while both induced cytoplasmic retention at 0.5 and 5 μM. Moreover, both stimulated double-strand breaks, enhancing H2AX phosphorylation, coincidentally with ORF1p nuclear localization. In NMuMG similar results were observed, since they heighten LINE-1 mRNA levels. CPF effect was through AhR and TGF-β1 signaling, whereas HCB action depends only of AhR. In addition, both pesticides increase ORF1p expression and nuclear localization. Our results provide experimental evidence that HCB and CPF exposure modify LINE-1 methylation levels and induce LINE-1 reactivation, suggesting that epigenetic mechanisms could contribute to pesticide-induced breast cancer progression. Fil: Miret, Noelia Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Zappia, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Altamirano, Gabriela Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Pontillo, Carolina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Zárate, Lorena Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Gomez, Ayelen Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Lasagna, Marianela. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; Argentina Fil: Cocca, Claudia Marcela. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; Argentina Fil: Kass, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Monczor, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina |
| Databáze: | OpenAIRE |
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