Other
16 Authors
- Cline JM,
- Min Y,
- Thornburg T,
- Kang JX,
- Wu J,
- Berquin IM,
- Edwards IJ,
- Thomas MJ,
- Wu H,
- Smith A,
- Perry D,
- Chen YQ,
- Wu R,
- Kulik G,
- Zhang H,
- D'Agostino R
| First Author | Berquin IM | Year | 2007 |
| Journal | J Clin Invest | Volume | 117 |
| Issue | 7 | Pages | 1866-75 |
| PubMed ID | 17607361 | Mgi Jnum | J:124208 |
| Mgi Id | MGI:3721033 | Doi | 10.1172/JCI31494 |
| Citation | Berquin IM, et al. (2007) Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids. J Clin Invest 117(7):1866-75 |
| abstractText | 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. |
