Putative genomics of the mechanism of action of the olive oil "Meditteranean diet"

1: Eur J Cancer. 2006 Jan 4; [Epub ahead of print] Links

A genomic explanation connecting "Mediterranean diet", olive oil and cancer: Oleic acid, the main monounsaturated Fatty acid of olive oil, induces formation of inhibitory "PEA3 transcription factor-PEA3 DNA binding site" complexes at the Her-2/neu (erbB-2) oncogene promoter in breast, ovarian and stomach cancer cells.

Menendez JA, Papadimitropoulou A, Vellon L, Colomer R, Lupu R.

Department of Medicine, Evanston Northwestern Healthcare Research Institute, 1001 University Place, Evanston, IL 60201, USA; Department of Medicine, Northwestern University Feinberg, School of Medicine, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.

Olive oil is an integral ingredient of the "Mediterranean diet" and accumulating evidence suggests that it may have a potential role in lowering risk of several cancers. We recently hypothesized that the anti-cancer actions of olive oil may relate to its monounsaturated fatty acid (MUFA) oleic acid (OA; 18:1n-9) content to specifically regulate oncogenes. In this study, transient transfection experiments with human Her-2/neu promoter-driven luciferase gene established the ability of OA to specifically repress the transcriptional activity of Her-2/neu gene. Gene repression was seen in tumour-derived cell lines with Her-2/neu gene amplification and overexpression, including SK-Br3 (56% reduction), SK-OV3 (75% reduction) and NCI-N87 (55% reduction) breast, ovarian and stomach cancer cell lines, respectively. Also marginal decreases in promoter activity were observed in cancer cells expressing physiological levels of Her-2/neu (20% reduction in MCF-7 breast cancer cells). Remarkably, OA treatment in Her-2/neu-overexpressing cancer cells was found to induce up-regulation of the Ets protein polyomavirus enhancer activator 3 (PEA3), a transcriptional repressor of Her-2/neu promoter. Also, an intact PEA3 DNA-binding-site at endogenous Her-2/neu gene promoter was essential for OA-induced repression of this gene. Moreover, OA treatment failed to decrease Her-2/neu protein levels in MCF-7/Her2-18 transfectants, which stably express full-length human Her-2/neu cDNA controlled by a SV40 viral promoter. OA-induced transcriptional repression of Her-2/neu through the action of PEA3 protein at the promoter level may represent a novel mechanism linking "Mediterranean diet" and cancer.

PMID: 16406575 [PubMed - as supplied by publisher]