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

Eur J Cancer. 2006 Oct;42(15):2425-32. doi: 10.1016/j.ejca.2005.10.016. Epub 2006 Jan 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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


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