Oleic acid induces ERK1/2 activation and AP-1 DNA binding activity through a mechanism involving Src kinase and EGFR transactivation in breast cancer cells.
GPR40 and GPR120 are G-protein-coupled receptors that can be activated by medium- and long-chain fatty acids. GPR40 is expressed in several breast cancer cell lines and its stimulation with oleic acid (OA) induces cell proliferation. However, the signal transduction pathways activated by OA have not been studied in detail. Our results demonstrate that both GPR40 and GPR120 are expressed in MCF-7 cells. Stimulation of MCF-7 and MDA-MB-231 cells with OA promoted the phosphorylation of ERK1/2 at Thr-202 and Tyr-204 and the formation of AP-1-DNA complex in a fashion dependent of Src kinase activity and EGFR transactivation. Furthermore, proliferation induced by OA is restricted to breast cancer cells in a fashion dependent of ERK1/2 activation and matrix metalloproteinases. In summary, our data indicate that proliferation induced by OA is restricted to breast cancer cells, and that ERK1/2 activation and AP-1-DNA complex formation are mediated by Src family kinases and transactivation of EGFR.
Soto-Guzman
Adriana
A
Departamento de Biologia Celular, Cinvestav-IPN, San Pedro Zacatenco, Mexico, DF 07360, Mexico.
Robledo
Teresa
T
Lopez-Perez
Mario
M
Salazar
Eduardo Perez
EP
D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*; D019061:src-Family Kinases / Q000378:metabolism*
D004273:DNA, Neoplasm; C473034:FFAR1 protein, human; C519853:FFAR4 protein, human; D043562:Receptors, G-Protein-Coupled; D018808:Transcription Factor AP-1; D019301:Oleic Acid; D066246:ErbB Receptors; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020782:Matrix Metalloproteinases