Differential effects of n-3 and n-6 polyunsaturated fatty acids on BRCA1 and BRCA2 gene expression in breast cell lines.
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.
Bernard-Gallon
Dominique J
DJ
Laboratoire d'Oncologie Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France.
Vissac-Sabatier
Cécile
C
Antoine-Vincent
David
D
Rio
Pascale G
PG
Maurizis
Jean-Claude
JC
Fustier
Pierre
P
Bignon
Yves-Jean
YJ
D016718:Arachidonic Acid / Q000494:pharmacology; D019313:BRCA1 Protein / Q000032:analysis; D024682:BRCA2 Protein / Q000032:analysis; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002846:Chromatography, Affinity; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D019398:Genes, BRCA1 / Q000187:drug effects*; D024522:Genes, BRCA2 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D005231:Fatty Acids, Unsaturated; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid