References
Query Results -- Details
MGI Accession ID: MGI:3721033
J Number: J:124208
Other Accession IDs:
Title: Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids.
Authors: Berquin IM; Min Y; Wu R; Wu J; Perry D; Cline JM; Thomas MJ; Thornburg T; Kulik G; Smith A; Edwards IJ; D'Agostino R; Zhang H; Wu H; Kang JX; Chen YQ
Journal: J Clin Invest
Volume: 117
Issue: 7
Date: 2007 Jul
Year: 2007
Pages: 1866-75
Review Status: Peer Reviewed
Abstract:
Although a causal role of genetic alterations in human cancer is well established, it is still unclear whether dietary fat can modulate cancer risk in a predisposed population. Epidemiological studies suggest that diets rich in omega-3 polyunsaturated fatty acids reduce cancer incidence. To determine the influence of fatty acids on prostate cancer risk in animals with a defined genetic lesion, we used prostate-specific Pten-knockout mice, an immune-competent, orthotopic prostate cancer model, and diets with defined polyunsaturated fatty acid levels. We found that omega-3 fatty acids reduced prostate tumor growth, slowed histopathological progression, and increased survival, whereas omega-6 fatty acids had opposite effects. Introducing an omega-3 desaturase, which converts omega-6 to omega-3 fatty acids, into the Pten-knockout mice reduced tumor growth similarly to the omega-3 diet. Tumors from mice on the omega-3 diet had lower proportions of phosphorylated Bad and higher apoptotic indexes compared with those from mice on omega-6 diet. Knockdown of Bad eliminated omega-3-induced cell death, and introduction of exogenous Bad restored the sensitivity to omega-3 fatty acids. Our data suggest that modulation of prostate cancer development by polyunsaturated fatty acids is mediated in part through Bad-dependent apoptosis. This study highlights the importance of gene-diet interactions in prostate cancer.
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