title: Dietary methionine restriction inhibits prostatic intraepithelial neoplasia in TRAMP mice.
abstract: BACKGROUND
  Prostate cancer (PCa) is a major aging-related disease for which little progress has been made in developing preventive strategies. Over the past several years, methionine restriction (MR), the feeding of a diet low in methionine (Met), has been identified as an intervention which significantly extends lifespan and reduces the onset of chronic diseases, including cancer, in laboratory animals. We, therefore, hypothesized that MR may be an effective strategy for inhibiting PCa.
  
  
  METHODS
  Control (0.86% Met) or MR (0.12% Met) diets were fed to 5-week old TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice, a well-characterized model for PCa. The mice were sacrificed at 16 weeks of age and prostate and other tissues were harvested for histological and biochemical analyses.
  
  
  RESULTS
  As previously reported, MR was associated with a decrease in body weight which was not associated with lowered food intake. MR led to significant reductions in the development of Prostatic Intraepithelial Neoplasia (PIN) lesions, specifically in the anterior and dorsal lobes of the prostate where the incidence of high-grade PIN was reduced by ∼50% (P < 0.02). The reduction in PIN severity was associated with 46-64% reductions in cell proliferation rates (P < 0.02) and plasma IGF-1 levels (P < 0.0001), which might, in part, explain the effects on carcinogenesis. Additionally, no adverse consequences of MR on immune function were observed in the TRAMP mice.
  
  
  CONCLUSIONS
  Overall, these findings indicate that MR is associated with a reduction in prostate cancer development in the TRAMP model and supports the continued development of MR as a potential PCa prevention strategy.
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Raghu
authors.initials: R
authors.lastname: Sinha
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Cooper
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Rogers
authors.forename: Indu
authors.initials: I
authors.lastname: Sinha
authors.forename: William J
authors.initials: WJ
authors.lastname: Turbitt
authors.forename: Ana
authors.initials: A
authors.lastname: Calcagnotto
authors.forename: Carmen E
authors.initials: CE
authors.lastname: Perrone
authors.forename: John P
authors.initials: JP
authors.lastname: Richie
mesh_terms: D065311:Adenocarcinoma in Situ / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D049109:Cell Proliferation; D004032:Diet; D004195:Disease Models, Animal; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000172:deficiency*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*
chemical_list: D007334:Insulin-Like Growth Factor I; D008715:Methionine
keywords: TRAMP; methionine restriction; prostate cancer; prostatic intraepithelial neoplasia; sulfur amino acids