The Regulation of the Mevalonate Pathway for the Prevention of Breast Cancer
Abstract
The central hypothesis we are addressing is that inhibition of mammary carcinogenesis by n-3 polyunsaturated fatty acids(PUFAs)can be accounted for by their inhibitory effect on the cholesterol biosynthesis (mevalonate) pathway. In Task 1, we have shown that the decrease in mammary gland HMG-CoA redustase seen in LDL-R -/- mice compared to +/+ mice fed a 7% n-6 diet persists when animals are fed a 20% n-6 PUFA diet. The inherent poor susceptibility of C57Bl mice to chemically induced mammary carcinogenesis, however, precluded further work on this model. In Task 2, we have shown that exogenous mevalonate delivered to nude mice via osmotic mini-pumps promoted the growth of MDA-MB-435 human breast cancer cells, a result that supports our hypothesis. In Task 3, we have optimized conditions for the growth and treatment of MDA-MB-435 and MCF-10A cells and shown that long chain n-3 and n-6 PUFAs have differential effects on HMG-CoA reductase activity in at least one cancer cell line compared to normal mammary epithelial cells. Our work will provide a basis for understanding the protective effects of n-3 PUFAs and perhaps other dietary factors on breast cancer development and may lead to mechanism-based strategies for the prevention of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA398054
Entities
People
- Michael C. Archer
Organizations
- University of Toronto