Document Detail


Effect of low-fat diet on development of prostate cancer and Akt phosphorylation in the Hi-Myc transgenic mouse model.
MedLine Citation:
PMID:  18413778     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Naoko Kobayashi; R James Barnard; Jonathan Said; Jenny Hong-Gonzalez; Dan M Corman; Melvin Ku; Ngan Bao Doan; Dorina Gui; David Elashoff; Pinchas Cohen; William J Aronson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  68     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-16     Completed Date:  2008-06-10     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3066-73     Citation Subset:  IM    
Affiliation:
Department of Urology, School of Medicine, University of California, Los Angeles, CA 90095-1738, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Diet, Fat-Restricted*
Genes, myc*
Humans
Male
Mice
Mice, Transgenic
Models, Animal
Oncogene Protein v-akt / genetics*
Prostatic Neoplasms / prevention & control*
Grant Support
ID/Acronym/Agency:
1R01CA100938/CA/NCI NIH HHS; P50 CA092131/CA/NCI NIH HHS; P50 CA092131-01A10005/CA/NCI NIH HHS; P50 CA92131-01A1/CA/NCI NIH HHS; R01 CA100938-04/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
EC 2.7.11.1/Oncogene Protein v-akt
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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