RGD Reference Report - Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids. - Rat Genome Database

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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 
Citation: Berquin IM, etal., J Clin Invest. 2007 Jul;117(7):1866-75.
RGD ID: 2292673
Pubmed: PMID:17607361   (View Abstract at PubMed)
PMCID: PMC1890998   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI31494   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Prostatic Neoplasms  ISOBad (Mus musculus)2292673; 2292673 RGD 
Prostatic Neoplasms  IMP 2292673 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bad  (BCL2-associated agonist of cell death)

Genes (Mus musculus)
Bad  (BCL2-associated agonist of cell death)

Genes (Homo sapiens)
BAD  (BCL2 associated agonist of cell death)


Additional Information