title: High animal fat intake enhances prostate cancer progression and reduces glutathione peroxidase 3 expression in early stages of TRAMP mice.
abstract: BACKGROUND
  Prostate cancer is the most frequently diagnosed cancer in Western men, and more men have been diagnosed at younger ages in recent years. A high-fat Western-style diet is a known risk factor for prostate cancer and increases oxidative stress.
  
  
  METHODS
  We evaluated the association between dietary animal fat and expression of antioxidant enzymes, particularly glutathione peroxidase 3 (GPx3), in the early stages of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Six-week-old male nontransgenic and TRAMP mice were placed on high animal fat (45% Kcal fat) or control (10% Kcal fat) diets and sacrificed after 5 or 10 weeks.
  
  
  RESULTS
  The histopathological score increased with age and high-fat diet consumption. The histopathological scores in dorsal and lateral lobes increased in the 10-week high-fat diet group (6.2±0.2 and 6.2±0.4, respectively) versus the 10-week control diet group (5.3±0.3 and 5.2±0.2, respectively). GPx3 decreased both at the mRNA and protein levels in mouse prostate. GPx3 mRNA expression decreased (∼36.27% and ∼23.91%, respectively) in the anterior and dorsolateral prostate of TRAMP mice fed a high-fat diet compared to TRAMP mice fed a control diet. Cholesterol treatment increased PC-3 human prostate cancer cell proliferation, decreased GPx3 mRNA and protein levels, and increased H2 O2 levels in culture medium. Moreover, increasing GPx3 mRNA expression by troglitazone in PC-3 cells decreased cell proliferation and lowered H2 O2 levels.
  
  
  CONCLUSIONS
  Dietary fat enhances prostate cancer progression, possibly by suppressing GPx3 expression and increasing proliferation of prostate intraepithelial neoplasia (PIN) epithelial cells.
authors: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors: Seo-Na
authors: SN
authors: Chang
authors: Juhee
authors: J
authors: Han
authors: Tamer Said
authors: TS
authors: Abdelkader
authors: Tae-Hyoun
authors: TH
authors: Kim
authors: Ji Min
authors: JM
authors: Lee
authors: Juha
authors: J
authors: Song
authors: Kyung-Sul
authors: KS
authors: Kim
authors: Jong-Hwan
authors: JH
authors: Park
authors: Jae-Hak
authors: JH
authors: Park
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059305:Diet, High-Fat; D018450:Disease Progression; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase
keywords: GPx3; TRAMP; cholesterol; high-fat diet; prostate cancer