title: Dietary n-3 polyunsaturated fatty acids fail to reduce prostate tumorigenesis in the PB-ErbB-2 x Pten(+/-) preclinical mouse model.
abstract: 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.affiliation: Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Sarada
authors.initials: S
authors.lastname: Vissapragada
authors.forename: Anup
authors.initials: A
authors.lastname: Ghosh
authors.forename: Lymor
authors.initials: L
authors.lastname: Ringer
authors.forename: Patricia
authors.initials: P
authors.lastname: Salinas
authors.forename: Amanda
authors.initials: A
authors.lastname: Brophy
authors.forename: Daniel
authors.initials: D
authors.lastname: Peaceman
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Kallakury
authors.forename: Partha P
authors.initials: PP
authors.lastname: Banerjee
authors.forename: Stanley T
authors.initials: ST
authors.lastname: Fricke
authors.forename: William
authors.initials: W
authors.lastname: Helfrich
authors.forename: Yi Chien
authors.initials: YC
authors.lastname: Lee
authors.forename: Richard
authors.initials: R
authors.lastname: Pestell
authors.forename: Philipp
authors.initials: P
authors.lastname: Scherer
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Tanowitz
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Avantaggiati
authors.forename: Leena
authors.initials: L
authors.lastname: Hilakivi-Clarke
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Olga C
authors.initials: OC
authors.lastname: Rodriguez
authors.forename: Chris
authors.initials: C
authors.lastname: Albanese
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D019927:Cyclin E / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D039642:Eukaryotic Initiation Factors; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019927:Cyclin E; D039642:Eukaryotic Initiation Factors; D015525:Fatty Acids, Omega-3; D047908:Intracellular Signaling Peptides and Proteins; D051059:PTEN Phosphohydrolase; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases; D051025:bcl-Associated Death Protein; C494820:Bad protein, mouse; C499527:Eif4ebp1 protein, mouse; C546843:mTOR protein, mouse; C487757:Pten protein, mouse
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