Apr. 13, 2008 New data suggest that dietary energy balance may affect the risk for skin tumor development. Researchers believe that these effects of dietary energy balance are mediated by changes in signaling through the epidermal growth factor receptor (EGFR) and the insulin-like growth factor 1 receptor (IGF-1R).
"We have demonstrated that dietary energy balance directly modulates activation of cell surface receptors, specifically the EGFR and the IGF-1R, which subsequently affects signaling through downstream pathways, such as Akt and mTOR. Negative energy balance inhibits, while positive energy balance enhances, signaling through these pathways, thereby modulating cellular growth, proliferation, and survival," said Tricia Moore, lead author of the study.
Dietary energy balance refers to the balance between caloric intake and energy expenditure, according to the report. Previous findings from both epidemiological and experimental studies suggest chronic positive energy balance, which can lead to obesity, increases the risk of developing multiple cancers. However, a negative energy balance state, as induced by calorie restriction, decreases these risks in most instances, the researchers said.
In the present study, the researchers used a two-stage skin carcinogenesis model to examine the effects of both positive and negative dietary energy balance on skin tumor promotion and progression. Groups of female mice received 25 nmol of 7,12-dimethylbenz(a)anthracene (DMBA), a cancer inducing chemical, and were then placed on one of four dietary treatment regimens to generate either a positive or negative energy balance state. After four weeks on their respective diets, the mice received two other cancer inducing chemicals (acetone, 3.4 nmol or 6.8 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA)) twice weekly for the duration of the study.
Negative energy balance, as induced by both 15 percent and 30 percent calorie restriction, led to inhibition of papilloma (benign skin tumors that can potentially lead to skin cancer) formation, depending on TPA dose, when compared to either positive energy balance inducing diet. Although tumor multiplicity, as measured by papillomas per mouse, was slightly higher among those receiving the more calorie dense fat diet, this was not different from the less calorie dense fat diet with either dose of TPA, the researchers noted. The impact of dietary energy balance manipulation on the conversion of papillomas to squamous cell carcinomas in this model of multistage skin carcinogenesis is also being assessed.
These researchers have also shown that dietary energy balance alters signaling through the Akt and mTOR pathways, both of which are related to TPA-mediated skin tumor development. They propose that the mechanism for the effect of dietary energy balance on Akt and mTOR signaling may be mediated, in part, by changes in serum IGF-1 levels, which then alters signaling through the IGF-1R and EGFR.
"These findings will provide the basis for future translational studies targeting the Akt/mTOR pathway via combinations of lifestyle (e.g., moderate calorie restriction regimens) and pharmacologic approaches for the prevention and control of obesity-related epithelial cancers in humans," said John DiGiovanni, Ph.D., director of M. D. Anderson Cancer Center -- Science Park Research Division, in whose lab this work is being conducted.
This research was presented at the American Association for Cancer Research 2008 Annual Meeting, April 12-16.
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