Effect of omega-6 polyunsaturated fatty acid (linoleic acid) on BRCA1 gene expression in MCF-7 cell line.
Dietary unsaturated fatty acids have been implicated in breast cancer. Since mutations in BRCA1 gene are known to predispose to breast cancers, and BRCA1 gene is known to be regulated by estradiol, the effect of linoleic acid, an omega-6-polyunsaturated fatty acid, with and without estradiol was studied for the expression of BRCA1 gene, in MCF-7 cell line, which has only one wild type allele. MCF-7 cells exposed to either linoleic acid or estradiol showed relatively greater number of colonies on soft agar, extent of proliferation and BRCA1 mRNA expression compared with controls. However, cells treated with both linoleic acid and estradiol showed significantly higher number of colonies, proliferation index and appreciably decreased expression of BRCA1 mRNA compared with controls or cells treated with linoleic acid or estradiol alone. The synergistic effects of these two agents were abrogated when indomethacin, an inhibitor of prostaglandin pathway, was added to the culture. From these observations it appears that diet rich in omega-6-polyunsaturated fatty acid like linoleic acid and endogenous estrogen may modulate BRCA1 gene expression thereby promoting breast cancer.
Kachhap
S K
SK
Cell Biology Division, Cancer Research Institute, Tata Memorial Centre, Parel, Mumbai, India.
Dange
P
P
Nath Ghosh
S
S
D000362:Agar / Q000378:metabolism; D000483:Alleles; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019398:Genes, BRCA1; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D019787:Linoleic Acid / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018076:DNA, Complementary; D012333:RNA, Messenger; D004958:Estradiol; D000362:Agar; D019787:Linoleic Acid; D007213:Indomethacin