title: Effect of low-fat diet on development of prostate cancer and Akt phosphorylation in the Hi-Myc transgenic mouse model.
abstract: This study evaluated the effect of dietary fat on prostate cancer development by using the Hi-Myc mouse transgenic prostate cancer model. Hi-Myc mice develop murine prostatic intraepithelial neoplasia (mPIN) as early as 2 to 4 weeks and invasive adenocarcinoma between 6 and 9 months due to the overexpression of human c-Myc in the mouse prostate. Three-week-old male Hi-Myc mice were placed on high-fat (HF; 42% Kcal) or low-fat (LF; 12% Kcal) diets, and equal caloric intake was maintained until euthanasia at 7 months. The number of mice that developed invasive adenocarcinoma at 7 months was 27% less in the LF diet group (12/28) compared with the HF diet group (23/33, P < 0.05). Epithelial cells in mPIN lesions in the LF group had a significantly lower proliferative index compared with epithelial cells in the HF group (21.7% versus 28.9%, P < 0.05). During the mPIN phase of carcinogenesis (4 months), the LF group had higher serum insulin-like growth factor (IGF) binding protein-1 levels (21.0 +/- 8.9 ng/mL versus 3.2 +/- 0.8 ng/mL, P < 0.05) relative to the HF group. Akt (Ser(473)) phosphorylation, Akt kinase activity, and phosphorylation of downstream targets of Akt in prostates were significantly reduced in the LF diet group compared with the HF group. We conclude that dietary fat reduction delays transition from mPIN to invasive cancer in this Myc-driven transgenic mouse model, possibly through suppression of the IGF-Akt pathway and decreased proliferation of mPIN epithelial cells.
authors.affiliation: Department of Urology, School of Medicine, University of California, Los Angeles, CA 90095-1738, USA.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kobayashi
authors.forename: R James
authors.initials: RJ
authors.lastname: Barnard
authors.forename: Jonathan
authors.initials: J
authors.lastname: Said
authors.forename: Jenny
authors.initials: J
authors.lastname: Hong-Gonzalez
authors.forename: Dan M
authors.initials: DM
authors.lastname: Corman
authors.forename: Melvin
authors.initials: M
authors.lastname: Ku
authors.forename: Ngan Bao
authors.initials: NB
authors.lastname: Doan
authors.forename: Dorina
authors.initials: D
authors.lastname: Gui
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
authors.forename: William J
authors.initials: WJ
authors.lastname: Aronson
mesh_terms: D000818:Animals; D018752:Diet, Fat-Restricted; D016259:Genes, myc; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D051058:Oncogene Protein v-akt / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000517:prevention & control*
chemical_list: D051058:Oncogene Protein v-akt