Effect of low-fat diet on development of prostate cancer and Akt phosphorylation in the Hi-Myc transgenic mouse model

Naoko Kobayashi, R. James Barnard, Jonathan Said, Jenny Hong-Gonzalez, Dan M. Corman, Melvin Ku, Bao Doan Ngan, Dorina Gui, David Elashoff, Pinchas Cohen, William J. Aronson

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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 (Ser473) 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.

Original languageEnglish (US)
Pages (from-to)3066-3073
Number of pages8
JournalCancer Research
Volume68
Issue number8
DOIs
StatePublished - Apr 15 2008

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Prostatic Intraepithelial Neoplasia
Fat-Restricted Diet
Transgenic Mice
Prostatic Neoplasms
Phosphorylation
Diet
Dietary Fats
Epithelial Cells
Prostate
Adenocarcinoma
Fats
Insulin-Like Growth Factor Binding Protein 1
Euthanasia
Somatomedins
Energy Intake
Carcinogenesis
Phosphotransferases
Serum
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kobayashi, N., Barnard, R. J., Said, J., Hong-Gonzalez, J., Corman, D. M., Ku, M., ... Aronson, W. J. (2008). Effect of low-fat diet on development of prostate cancer and Akt phosphorylation in the Hi-Myc transgenic mouse model. Cancer Research, 68(8), 3066-3073. https://doi.org/10.1158/0008-5472.CAN-07-5616

Effect of low-fat diet on development of prostate cancer and Akt phosphorylation in the Hi-Myc transgenic mouse model. / Kobayashi, Naoko; Barnard, R. James; Said, Jonathan; Hong-Gonzalez, Jenny; Corman, Dan M.; Ku, Melvin; Ngan, Bao Doan; Gui, Dorina; Elashoff, David; Cohen, Pinchas; Aronson, William J.

In: Cancer Research, Vol. 68, No. 8, 15.04.2008, p. 3066-3073.

Research output: Contribution to journalArticle

Kobayashi, N, Barnard, RJ, Said, J, Hong-Gonzalez, J, Corman, DM, Ku, M, Ngan, BD, Gui, D, Elashoff, D, Cohen, P & Aronson, WJ 2008, 'Effect of low-fat diet on development of prostate cancer and Akt phosphorylation in the Hi-Myc transgenic mouse model', Cancer Research, vol. 68, no. 8, pp. 3066-3073. https://doi.org/10.1158/0008-5472.CAN-07-5616
Kobayashi, Naoko ; Barnard, R. James ; Said, Jonathan ; Hong-Gonzalez, Jenny ; Corman, Dan M. ; Ku, Melvin ; Ngan, Bao Doan ; Gui, Dorina ; Elashoff, David ; Cohen, Pinchas ; Aronson, William J. / Effect of low-fat diet on development of prostate cancer and Akt phosphorylation in the Hi-Myc transgenic mouse model. In: Cancer Research. 2008 ; Vol. 68, No. 8. pp. 3066-3073.
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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 (Ser473) 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.",
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AU - Corman, Dan M.

AU - Ku, Melvin

AU - Ngan, Bao Doan

AU - Gui, Dorina

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AU - Cohen, Pinchas

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