Differential effects of <I>n</I>-3 and <I>n</I>-6 polyunsaturated fatty acids on <I>BRCA1</I> and <I>BRCA2</I> gene expression in breast cell lines

Abstract

Current evidence strongly supports a role for the breast tumour suppressor genes, BRCA1 and BRCA2, in both normal development and carcinogenesis. In vitro observations reported that BRCA1 and BRCA2 are expressed in a cell cycle-dependent manner. Interestingly, differences in the actions of n-3 and n-6 polyunsaturated fatty acids have been observed: while the n-3 polyunsaturated fatty acids have been described to reduce pathological cell growth, the n-6 polyunsaturated fatty acids have been found to induce tumour proliferation. Here, we examined the expression of BRCA1 and BRCA2 in breast cell lines after treatment with polyunsaturated fatty acids. Real-time quantitative polymerase chain reaction determinations conclusively demonstrated increases in BRCA1 and BRCA2 mRNA expressions in MCF7 and MDA-MB 231 tumour cell lines after treatment with n-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid), but no variation was noticed with the n-6 polyunsaturated fatty acid (arachidonic acid). On the other hand, no variation of the expression of BRCA1 and BRCA2 mRNA was detected in MCF10a normal breast cell line treated by polyunsaturated fatty acids. The level of BRCA1 and BRCA2 proteins quantified by affinity chromatography remained unchanged in tumour (MCF7, MDA-MB 231) and normal (MCF10a) breast cell lines. We suggest the presence of a possible transcriptional or post-transcriptional regulation of BRCA1 and BRCA2 after n-3 polyunsaturated fatty acid treatment in breast tumour cells.

Stearidonic acid-enriched flax oil reduces the growth of human breast cancer in vitro and in vivo

“…Increases in EPA and DHA concentration of PL have been demonstrated to decrease cell proliferation and increase apoptosis, by changes in EGFR/AKT/NFkappaB cell survival pathway or by inducing CD95-mediated apoptosis [2][3][4]15]. EPA, but not DHA, increased with SO treatment in the current study, and this fatty acid has been demonstrated to inhibit human breast cancers both in vitro [1][2][3][4][49][50][51][52] and in vivo [7,50] and induce apoptosis [2,4,53]. DPA was increased with SO treatment by more than threefold in tumorigenic cells.…”

The Janus Face of Lipids in Human Breast Cancer: How Polyunsaturated Fatty Acids Affect Tumor Cell Hallmarks

“…On the contrary PUFAs are generally regarded as safe compounds that are well tolerated and produce few side effects. Their effects on nontumorigenic cells have not been fully elucidated, but some studies suggest that when provided at concentrations that inhibit tumor cell growth, n − 3 PUFA exert little or no cytotoxic effects on normal breast cells [17, 18, 108]. Clinical studies are ongoing to show the DHA-improved outcome of chemotherapy in patients with metastatic breast cancer [109, 110].…”

Dietary Fat in Breast Cancer Survival

“…For example, linoleic acid has been shown to decrease protein levels of tumor suppressor p53, whereas DHA up-regulated expression of p53 (19, 60). Furthermore, dietary lipids have been shown to affect the expression of the suppressor genes breast cancer susceptibility gene 1 (BRCA1) and BRCA2, two genes implicated repeatedly in breast cancer recurrence (10). Omega-3 LCPUFA increased BRCA1 and BRCA2 mRNA expression (10).…”

“…Furthermore, dietary lipids have been shown to affect the expression of the suppressor genes breast cancer susceptibility gene 1 (BRCA1) and BRCA2, two genes implicated repeatedly in breast cancer recurrence (10). Omega-3 LCPUFA increased BRCA1 and BRCA2 mRNA expression (10). …”