Document Detail


Dietary n-3 polyunsaturated fatty acids fail to reduce prostate tumorigenesis in the PB-ErbB-2 x Pten(+/-) preclinical mouse model.
MedLine Citation:
PMID:  20404514     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Sarada Vissapragada; Anup Ghosh; Lymor Ringer; 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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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-05-15
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  9     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-31     Completed Date:  2010-09-03     Revised Date:  2013-06-18    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1824-9     Citation Subset:  IM    
Affiliation:
Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, DC, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carrier Proteins / metabolism
Cyclin E / metabolism
Disease Models, Animal
Disease Progression
Fatty Acids, Omega-3 / therapeutic use*
Intracellular Signaling Peptides and Proteins / metabolism
Male
Mice
PTEN Phosphohydrolase / genetics*,  metabolism
Phosphoproteins / metabolism
Phosphorylation
Prostatic Neoplasms / pathology,  prevention & control*
Protein-Serine-Threonine Kinases / metabolism
Receptor, erbB-2 / genetics*,  metabolism
TOR Serine-Threonine Kinases
bcl-Associated Death Protein / metabolism
Grant Support
ID/Acronym/Agency:
R01 CA102746/CA/NCI NIH HHS; R01 CA129003/CA/NCI NIH HHS; R01CA102746/CA/NCI NIH HHS; R01CA129003/CA/NCI NIH HHS; R03 AG020337/AG/NIA NIH HHS; U54 CA100970/CA/NCI NIH HHS; U54CA100970-02/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Bad protein, mouse; 0/Carrier Proteins; 0/Cyclin E; 0/Eif4ebp1 protein, mouse; 0/Fatty Acids, Omega-3; 0/Intracellular Signaling Peptides and Proteins; 0/Phosphoproteins; 0/bcl-Associated Death Protein; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.1/mTOR protein, mouse; EC 2.7.10.1/Receptor, erbB-2; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 3.1.3.48/Pten protein, mouse; EC 3.1.3.67/PTEN Phosphohydrolase
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