title: Benzo-[a]-pyrene induces FAK activation and cell migration in MDA-MB-231 breast cancer cells.
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.
authors: Departamento de Toxicologia, Av IPN #2508, San Pedro Zacatenco, Mexico, DF, 07360, Mexico.
authors: Rocio
authors: R
authors: Castillo-Sanchez
authors: Socrates
authors: S
authors: Villegas-Comonfort
authors: Octavio
authors: O
authors: Galindo-Hernandez
authors: Rocio
authors: R
authors: Gomez
authors: Eduardo Perez
authors: EP
authors: Salazar
mesh_terms: D001580:Benzopyrenes / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis; D008084:Lipoxygenase / Q000187:drug effects / Q000378:metabolism; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001580:Benzopyrenes; D039302:Integrin alphaVbeta3; D008084:Lipoxygenase; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9