Genetic Regulation of Lipid Biogenesis in Human Breast Cancer
Annual rept. 1 Jul 1999-1 Jul 2000
Pagination or Media Count:
It has been shown that dietary n-6 polyunsaturated fatty acids PUFAs promote tumorigenesis and maintain growth of breast cancer cell lines, while n-3 PUFAs generally reduce the incidence and development of cancer and inhibit growth in cell culture. We investigated the effects of various n-6 and n-3 PUFAs, on lipogenic gene expression in two breast cancer cell lines, MDA-MB-231 a p53-- cell line and MCF-7 a p53 cell line. In both lines, we showed that PUFAs repressed the expression of two important genes in the fatty acid biosynthesis pathway, fatty acid synthase FAS and stearoyl-CoA desaturase-1 SCD-1. In addition we showed that this PUFA-induced repression was mediated through the sterol regulatory element binding protein 1 a SREBP-1a and not the mutant p53 protein as we had previously hypothesized. SREBP is a newly identified and critical central activator of both the cholesterol and fatty acid biosynthesis pathways.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research