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Benzo-[a]-pyrene induces FAK activation and cell migration in MDA-MB-231 breast cancer cells
Authors:Rocio Castillo-Sanchez  Socrates Villegas-Comonfort  Octavio Galindo-Hernandez  Rocio Gomez  Eduardo Perez Salazar
Affiliation:1. Departamento de Toxicologia, Av IPN #2508, San Pedro Zacatenco, Mexico, DF, 07360, Mexico
2. Departamento de Biologia Celular, Cinvestav-IPN, Av IPN #2508, San Pedro Zacatenco, Mexico, DF, 07360, Mexico
Abstract:Benzo-[a]-pyrene (B[a]P) is a family member of polycyclic aromatic hydrocarbons and a widespread environmental pollutant. It is a mammary carcinogen in rodents and contributes to the development of human breast cancer. However, the signal transduction pathways induced by B[a]P and its role in breast cancer progression have not been studied in detail. Here, we demonstrate that B[a]P induces cell migration through a lipoxygenase- and Src-dependent pathway, as well as the activation of focal adhesion kinase, Src, and the extracellular signal-regulated kinase 2 in MDA-MB-231 breast cancer cells. However, B[a]P is not able to promote migration in the mammary nontumorigenic epithelial cells MCF12A. Moreover, B[a]P promotes an increase of αvβ3 integrin–cell surface levels and an increase of metalloproteinase (MMP)-2 and MMP-9 secretions. In summary, our findings demonstrate that B[a]P induces the activation of signal transduction pathways and biological processes involved in the invasion/metastasis process in MDA-MB-231 breast cancer cells.
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