Objective: In women, alcohol consumption increases breast cancer risk and decreases type-2 diabetes risk. How alcohol mediates these differential effects is not known. Our hypothesis is that alcohol consumption increases breast cancer development and decreases type-2 diabetes risk by a similar mechanism. Therefore, the objective of the present studies is to determine if alcohol consumption affects insulin sensitivity and mammary tumor development by a similar mechanism (or mechanisms). Methods: To determine glucose regulation and insulin sensitivity, we performed insulin tolerance tests (ITT) and glucose tolerance tests (GTT) in mice which had free access to water or 20%w/v ethanol in the drinking water. To determine the effects of alcohol consumption on mammary tumor development, mice were injected subcutaneously with mammary tumor cells. Furthermore, to elucidate whether alcohol has a direct effect on the metastatic ability of breast cancer cells, we determined the effects of alcohol on the invasiveness of T47D human breast cancer cells via in vitro studies. Results: Results show that alcohol consumption improves insulin sensitivity in overweight and obese mice. Moreover, results show that alcohol consumption improves insulin sensitivity in mice without affecting body weight or body fat levels. With respect to mammary cancer, results from in vitro studies show that alcohol consumption increases the metastatic phenotype of breast cancer cells. In animal studies, we show that alcohol consumption promotes mammary tumor development. Conclusions: In summary, we show that alcohol consumption improves insulin sensitivity, promotes tumor development, and increases the metastatic phenotype of breast cancer cells. Thus, we present a suitable animal model where we can determine if alcohol consumption affects insulin sensitivity and mammary tumor development by a similar mechanism (or mechanisms). Using the animal model presented here can lead to a better understanding of how alcohol increases breast cancer risk, and thus can accelerate the development of new breast cancer prevention and treatment strategies.
99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA