Identification of a molecular signature underlying inhibition of mammary carcinoma growth by dietary N-3 fatty acids.

Abstract

An increased ratio of dietary n-3 relative to n-6 fatty acids has been shown to inhibit the development of mammary cancer in animal models. However, the molecular mechanisms by which n-3 fatty acids affect tumor growth remain unknown. Here, we investigated the effects of varying dietary ratios of n-3:n-6 fatty acids on cell signaling in a rat model of chemically induced mammary carcinoma. Cell proliferation was reduced by 60% in carcinomas from the high n-3:n-6 treatment group compared with the low n-3:n-6 treatment group. These changes were associated with decreased cyclin-D1 and phospho-retinoblastoma protein expression and increased levels of cyclin-dependent kinase inhibitors, CIP1 (p21) and KIP1 (p27). In addition, the apoptotic index was increased in carcinomas from the high n-3:n-6 group and was associated with elevated apoptotic protease-activating factor 1 and a higher ratio of Bax/Bcl-2. Interestingly, changes in protein expression were consistent with reduced inflammation and suppressed mTOR activity, and the molecular signature associated with high n-3:n-6 treatment revealed changes in PPARγ activation and suppression of lipid synthesis. Together, our findings indicate that the molecular effects of high dietary n-3 to n-6 ratios are heterogeneous in nature but point to consistent changes in lipid metabolism pathways, which may serve as potential therapeutic targets for cancer prevention and control. This study identifies the pathways modulated by dietary fatty acid ratios in a rat model of breast cancer, with implications for cancer prevention.

• Authors: Weiqin Jiang, Zongjian Zhu, John N McGinley, Karam El Bayoumy, Andrea Manni, Henry J Thompson
• Journal: Cancer research (Cancer Res) Vol. 72 Issue 15 Pg. 3795-806 (Aug 01 2012) ISSN: 1538-7445 [Electronic] United States
• PMID: 22651929 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2012 AACR.

Chemical References

• Carcinogens
• Dietary Fats
• Fatty Acids, Omega-3
• Methylnitrosourea

Topics

• Animals
• Carcinogens
• Carcinoma (chemically induced, genetics, pathology, prevention & control)
• Cell Proliferation (drug effects)
• Cluster Analysis
• Dietary Fats (pharmacology, therapeutic use)
• Down-Regulation (drug effects, genetics)
• Drug Evaluation, Preclinical
• Fatty Acids, Omega-3 (pharmacology, therapeutic use)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Mammary Neoplasms, Experimental (chemically induced, genetics, pathology, prevention & control)
• Methylnitrosourea
• Microarray Analysis
• Models, Biological
• Rats
• Validation Studies as Topic