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 language | English (US) |
|---|---|
| Pages (from-to) | 3066-3073 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 68 |
| Issue number | 8 |
| DOIs | |
| State | Published - Apr 15 2008 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
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 journal › Article
}
TY - JOUR
T1 - Effect of low-fat diet on development of prostate cancer and Akt phosphorylation in the Hi-Myc transgenic mouse model
AU - Kobayashi, Naoko
AU - Barnard, R. James
AU - Said, Jonathan
AU - Hong-Gonzalez, Jenny
AU - Corman, Dan M.
AU - Ku, Melvin
AU - Ngan, Bao Doan
AU - Gui, Dorina
AU - Elashoff, David
AU - Cohen, Pinchas
AU - Aronson, William J.
PY - 2008/4/15
Y1 - 2008/4/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=42349094502&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42349094502&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-5616
DO - 10.1158/0008-5472.CAN-07-5616
M3 - Article
C2 - 18413778
AN - SCOPUS:42349094502
VL - 68
SP - 3066
EP - 3073
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 8
ER -