Dietary n-3 polyunsaturated fatty acids fail to reduce prostate tumorigenesis in the PB-ErbB-2 x Pten(+/-) preclinical mouse model.
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.
Vissapragada
Sarada
S
Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, DC, USA.
Ghosh
Anup
A
Ringer
Lymor
L
Salinas
Patricia
P
Brophy
Amanda
A
Peaceman
Daniel
D
Kallakury
Bhaskar
B
Banerjee
Partha P
PP
Fricke
Stanley T
ST
Helfrich
William
W
Lee
Yi Chien
YC
Pestell
Richard
R
Scherer
Philipp
P
Tanowitz
Herbert B
HB
Avantaggiati
Maria Laura
ML
Hilakivi-Clarke
Leena
L
Lisanti
Michael P
MP
Rodriguez
Olga C
OC
Albanese
Chris
C
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
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
J Urol. 2005 Mar;173(3):732-6
15711258
Nat Genet. 1998 Aug;19(4):348-55
9697695
Am J Clin Nutr. 2008 Nov;88(5):1297-303
18996866
J Urol. 2007 Jan;177(1):97-101; discussion 101
17162011
Cancer Prev Res (Phila). 2008 Jun;1(1):65-76
19138937
J Clin Invest. 2007 Jul;117(7):1866-75
17607361
Cell Cycle. 2007 Aug 1;6(15):1946-50
17671425
Urology. 2005 Jul;66(1):108-13
15992911
Prostate. 2006 May 15;66(7):708-17
16425198
Cancer Res. 2007 May 1;67(9):4364-72
17483350
Am J Pathol. 2009 Jun;174(6):2051-60
19443706
Nat Med. 2007 Jul;13(7):803-11
17603492
Obes Res. 2004 Dec;12(12):1930-5
15687393
J Urol. 2004 Aug;172(2):520-4
15247719
J Biol Chem. 2009 Mar 27;284(13):8855-65
19171933
J Cell Physiol. 1990 Oct;145(1):162-72
2211839
J Neurosci Methods. 2004 Jun 15;136(1):99-102
15126050
Am J Clin Nutr. 2004 Jul;80(1):204-16
15213050