Bernard-Gallon Dominique J, Vissac-Sabatier Cécile, Antoine-Vincent David, Rio Pascale G, Maurizis Jean-Claude, Fustier Pierre, Bignon Yves-Jean
Laboratoire d'Oncologie Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France.
Br J Nutr. 2002 Apr;87(4):281-9. doi: 10.1079/BJNBJN2002522.
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.
目前的证据有力地支持了乳腺肿瘤抑制基因BRCA1和BRCA2在正常发育和致癌过程中的作用。体外观察报告称，BRCA1和BRCA2以细胞周期依赖性方式表达。有趣的是，已观察到n-3和n-6多不饱和脂肪酸作用的差异：虽然n-3多不饱和脂肪酸已被描述为可减少病理性细胞生长，但n-6多不饱和脂肪酸已被发现可诱导肿瘤增殖。在此，我们检测了多不饱和脂肪酸处理后乳腺细胞系中BRCA1和BRCA2的表达。实时定量聚合酶链反应测定最终证实，用n-3多不饱和脂肪酸（二十碳五烯酸和二十二碳六烯酸）处理后，MCF7和MDA-MB 231肿瘤细胞系中BRCA1和BRCA2 mRNA表达增加，但n-6多不饱和脂肪酸（花生四烯酸）处理后未观察到变化。另一方面，用多不饱和脂肪酸处理的MCF10a正常乳腺细胞系中未检测到BRCA1和BRCA2 mRNA表达的变化。通过亲和色谱法定量的BRCA1和BRCA2蛋白水平在肿瘤（MCF7、MDA-MB 231）和正常（MCF10a）乳腺细胞系中保持不变。我们认为在乳腺肿瘤细胞中，n-3多不饱和脂肪酸处理后可能存在对BRCA1和BRCA2的转录或转录后调控。
