The risk for skin cancer development may be influenced by dietary energy balance, a new study on rodents has suggested. This risk is regulated by signalling through the epidermal growth factor receptor (EGFR) and the insulin-like growth factor 1 receptor (IGF-1R).
The study suggests that dietary energy balance refers to the balance between caloric intake and energy expenditure.
"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.
According to earlier research, while chronic positive energy balance, which can lead to obesity, increases the risk of developing multiple cancers, a negative energy balance state, as induced by calorie restriction, decreases these risks in most instances.
For the current study, a two-stage skin carcinogenesis model was used to determine the effects of both positive and negative dietary energy balance on skin tumor promotion and progression.
The researchers gave groups of female mice 25 nmol of 7,12-dimethylbenz(a)anthracene (DMBA), a cancer inducing chemical, and then placed them 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.
It was found that negative energy balance, as induced by both 15 percent and 30 percent calorie restriction, led to inhibition of papilloma (benign skin tumours that can potentially lead to skin cancer) formation, depending on TPA dose, when compared to either positive energy balance inducing diet.
The researchers noted that although tumour multiplicity, as measured by papillomas per mouse, was slightly higher among those receiving the more calorie dense fat diet, it was not different from the less calorie dense fat diet with either dose of TPA.
It was also shown that dietary energy balance alters signaling through the Akt and mTOR pathways, both of which are related to TPA-mediated skin tumour development. Later, they proposed that the mechanism for the effect of dietary energy balance on Akt and mTOR signaling may be regulated, partly 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, in whose lab this work is being conducted.