Differential effects ofn-3 andn-6 polyunsaturated fatty acids onBRCA1andBRCA2gene expression in breast cell lines

Abstract

Current evidence strongly supports a role for the breast tumour suppressor genes,BRCA1andBRCA2, in both normal development and carcinogenesis.In vitroobservations reported thatBRCA1andBRCA2are expressed in a cell cycle-dependent manner. Interestingly, differences in the actions ofn-3 andn-6 polyunsaturated fatty acids have been observed: while then-3 polyunsaturated fatty acids have been described to reduce pathological cell growth, then-6 polyunsaturated fatty acids have been found to induce tumour proliferation. Here, we examined the expression ofBRCA1andBRCA2in breast cell lines after treatment with polyunsaturated fatty acids. Real-time quantitative polymerase chain reaction determinations conclusively demonstrated increases inBRCA1andBRCA2mRNA expressions in MCF7 and MDA-MB 231 tumour cell lines after treatment withn-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid), but no variation was noticed with then-6 polyunsaturated fatty acid (arachidonic acid). On the other hand, no variation of the expression ofBRCA1andBRCA2mRNA was detected in MCF10a normal breast cell line treated by polyunsaturated fatty acids. The level ofBRCA1andBRCA2proteins 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 ofBRCA1andBRCA2aftern-3 polyunsaturated fatty acid treatment in breast tumour cells.