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.

Abstract

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.

• Authors: Javier A Menendez, Adriana Papadimitropoulou, Luciano Vellon, Ruth Lupu
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 42 Issue 15 Pg. 2425-32 (Oct 2006) ISSN: 0959-8049 [Print] England
• PMID: 16406575 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Olive Oil
• Plant Oils
• Transcription Factors
• transcription factor PEA3
• Oleic Acid
• Receptor, ErbB-2

Topics

• Breast Neoplasms (genetics, prevention & control)
• Cell Line, Tumor
• Diet, Mediterranean
• Female
• Gene Expression Regulation, Neoplastic (drug effects, genetics)
• Humans
• Immunoblotting
• Neoplasms (genetics, prevention & control)
• Oleic Acid (administration & dosage, pharmacology)
• Olive Oil
• Ovarian Neoplasms (genetics, prevention & control)
• Plant Oils (administration & dosage, chemistry)
• Receptor, ErbB-2 (antagonists & inhibitors, drug effects)
• Risk Factors
• Stomach Neoplasms (genetics, prevention & control)
• Transcription Factors (biosynthesis, drug effects)