Dietary n-3 polyunsaturated fatty acids fail to reduce prostate tumorigenesis in the PB-ErbB-2 x Pten(+/-) preclinical mouse model
| Autor: | Sarada Vissapragada, Anup Ghosh, Lymor Ringer, Paul Sirajuddin, Patricia Salinas, Amanda Brophy, Daniel Peaceman, Bhaskar Kallakury, Partha P. Banerjee, Stanley T. Fricke, William Helfrich, Yi Chien Lee, Richard Pestell, Philipp Scherer, Herbert B. Tanowitz, Maria Laura Avantaggiati, Leena Hilakivi-Clarke, Michael P. Lisanti, Olga C. Rodriguez, Chris Albanese |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Cyclin E Receptor ErbB-2 Diet and obesity Context (language use) Cell Cycle Proteins Protein Serine-Threonine Kinases Article Mice ErbB Internal medicine Fatty Acids Omega-3 medicine PTEN Animals Eukaryotic Initiation Factors Phosphorylation Molecular Biology PI3K/AKT/mTOR pathway Adaptor Proteins Signal Transducing chemistry.chemical_classification biology TOR Serine-Threonine Kinases Intracellular Signaling Peptides and Proteins PTEN Phosphohydrolase Prostatic Neoplasms Cell Biology Phosphoproteins Disease Models Animal Endocrinology chemistry biology.protein Disease Progression bcl-Associated Death Protein Carrier Proteins Corn oil Developmental Biology Polyunsaturated fatty acid |
| Zdroj: | Cell cycle (Georgetown, Tex.). 9(9) |
| ISSN: | 1551-4005 |
| Popis: | Diet and obesity, and their associated metabolic alterations, are some of the fastest-growing causes of disease and death in America. Findings from epidemiological studies correlating obesity, the sources of dietary fat and prostate cancer (PCa) are conflicting. We have previously shown that 15% of PB-ErbB-2 x pten(+/-) mice developed PCa and exhibited increased phosphorylated 4E-BP1, but not the key PI3-kinase intermediary phospho-protein, mTOR, when maintained on unrefined mouse chow. We report herein that 100% of animals fed refined, westernized AIN-93-based diets containing corn oil developed PCa by 12 months of age. Increases in visceral fat and mTO R activation in the tumors were also observed. Furthermore, nuclear cyclin E levels were significantly induced by the AIN-93-corn oil-based diets versus chow. Replacing 50% of the corn oil with menhaden oil, with 21% of its triglycerides being n-3 PUFA's, had no effect on tumorigenesis, fat deposition, cyclin E or mTOR. Phosphorylated BAD levels were similar in the tumors of mice in all three diets. Our data demonstrated that in the context of our preclinical model, components of crude chow, but not dietary n-3 PUFAs, protect against PCa progression. In addition, these data establish phosphorylated mTOR, nuclear cyclin E and visceral fat deposits as possible biomarkers of increased dietary risk for PCa. |
| Databáze: | OpenAIRE |
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