A genomic explanation linking breast cancer, “Mediterranean diet” and olive oil: Olive oil's monounsaturated fatty acid oleic acid transcriptionally regulates the co-ordinate expression of Fatty Acid Synthase (Oncogenic antigen-519), Her-2/neu (erbB-2) and PEA3 genes in breast cancer cells.
Authors: Michela Padovani, Jackie A. Lavigne, Gadisetti V R Chandramouli, Susan N. Perkins, Carl J. Barrett, Stephen D. Hursting, Michelle L. Bennett, David Berrigan
Journal: Cancer Research (2006)

5747   The final proof about the specific mechanisms by which the different components of olive oil, the principal source of fat in a typical Mediterranean diet, exert their potential protective effects on the promotion and progression of breast cancer requires further investigations. Interestingly, exogenous supplementation of breast cancer cells with OA has been found to significantly down-regulate the expression and activation status of Her-2/ neu  ( erb B-2), a well-characterized oncogene playing a key role in the etiology and progression of breast cancer. Fatty Acid Synthase (FAS), the key enzyme responsible for the endogenous biogenesis of fatty acids, is up-regulated in about 50% of breast cancers, is an indicator of poor prognosis and has been functionally associated with Her2/ neu  in a bi-directional manner. Her-2/ neu  overexpression stimulates the activity of FAS gene promoter, while FAS blockade indirectly suppresses Her-2/ neu  overexpression by up-regulating the  Ets  DNA-binding protein PEA3, a potent  trans -repressor of the Her-2/ neu  gene promoter activity. We here investigated the effects of exogenous supplementation with OA on the transcriptional activity of Her-2/ neu , FAS and PEA3 genes. To study this issue we performed transient transfection experiments with a Luciferase gene driven by the FAS, PEA3 and  erb B-2 promoters in a panel of breast cancer cell lines including MCF-7, MCF-7/Her2-18, MCF-7/HRG, MDA-MB-231, MDA-MB-435, and BT-474 cells, which differentially express FAS, Her-2/ neu  and the pro-metastatic growth factor Heregulin (HRG). Our results established the ability of OA to specifically repress the activity of the Her-2/ neu  wild-type gene promoter in breast cancer cell lines naturally exhibiting Her-2/ neu  gene amplification and overexpression. OA treatment significantly reduced FAS promoter activity in Her-2/ neu -overexpressing BT-474 and HRG-overexpressing MDA-MB-231 cells, while it failed to modulate FAS gene promoter activity in Her-2/ neu - and HRG-negative MCF-7 cells. OA treatment completely reversed Her-2/ neu - and HRG-induced up-regulation of FAS promoter activity in Her-2/ neu - and HRG-overexpressing MCF-7/Her2-18 and MCF-7/HRG derivatives. Interestingly, OA exposure significantly stimulated transcription from a PEA3 promoter-Luciferase reporter, while a Her-2/ neu  promoter bearing a mutated sequence at the PEA3-binding site was not subject to negative regulation by OA. These findings reveal that OA-coordinated expression patterns of cancer genes such as FAS, PEA3 and Her-2/ neu  should be considered a previously unrecognized genomic explanation linking olive oil-rich “Mediterranean diet” and breast cancer promotion and progression.