Division of Pharmacology & Toxicology, The University of Texas at Austin, 1400 Barbara Jordan Boulevard, Room 2.228, Austin, TX, 78723, United States.
Male Hi-Myc mice were placed on three dietary regimens [30% calorie restriction (CR), overweight control (modified AIN76A with 10kcal% fat), and a diet-induced obesity regimen (DIO) 60kcal% fat]. All diet groups had approximately similar incidence of hyperplasia and low grade PIN in the ventral prostate at 3 and 6 months of age. However, 30% CR significantly reduced the incidence of in situ adenocarcinomas at 3 months compared to the DIO group and at 6 months compared to both the overweight control and DIO groups. Furthermore, the DIO regimen significantly increased the incidence of adenocarcinoma with aggressive stromal invasion, as compared to the overweight control group (96% vs. 65% respectively, p=0.02) at the 6 month time point. Additionally, at both 3 and 6 months, only in situ carcinomas were observed in mice maintained on the 30% CR diet. Relative to overweight control, DIO increased, while 30% CR reduced activation of Akt, mTORC1, Stat3 and NFκB (p65) in ventral prostate. DIO also significantly increased (and 30% CR decreased) numbers of T-lymphocytes and macrophages in the ventral prostate compared to overweight control. The mRNA levels for IL1α, IL1β, IL6, IL7, IL23, IL27, NFκB1 (p50), TNFα and VEGF family members were significantly increased in the ventral prostate of the DIO group compared to both the overweight control and 30% CR diet groups. Collectively, these findings suggest that enhanced growth factor (Akt/mTORC1 and Stat3) and inflammatory (NFκB, cytokines) signaling may play a role in dietary energy balance effects on prostate cancer progression in Hi-Myc mice.
Written by:
Blando J, Moore T, Hursting SD, Jiang G, Saha A, Beltran L, Shen J, Repass J, Strom SS, Digiovanni J. Are you the author?
Reference: Cancer Prev Res (Phila). 2011 Sep 27. Epub ahead of print.
doi: 10.1158/1940-6207.CAPR-11-0182
PubMed Abstract
PMID: 21952584
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