Does Skeletal Muscle Mass Influence Breast Cancer Evaluating Mammary Tumorigenesis and Progression Genetically Hyper-Muscular Mice

摘要

Epidemiologic evidence demonstrates that caloric restriction and physical activity independently reduce breast cancer. Conversely, obesity and insulin resistance are associated with increased breast cancer incidence, metastasis and mortality. To date, no studies have addressed the role of skeletal muscle in breast cancer. To determine the effect of skeletal muscle mass on breast cancer, we are measuring rates of chemically induced mammary tumorigenesis and progression in genetically hypermuscular mice. Mice lacking the skeletal muscle-specific muscle growth inhibitor myostatin and mice expressing a dominant negative form of the myostatin receptor, Activin Receptor Type IIB, display heightened muscle mass. In order to induce mammary cancer in these mice, we administered a combination of a tumor promoter, medroxyprogesterone acetate, and a carcinogen, dimethylbenz-a-anthracene, using a defined protocol. Unfortunately, we have experienced both high nontumor associated mortality and low fertility, slowing progress of this study and requiring us to seek a no-cost extension of the project. We have resolved the environmental issues leading to high pup mortality and refined the MPA/DMBA model to produce 100% tumor incidence with minimal lethality and are continuing the study. By the completion of this study in 12-18 months, tumor latency, size, stage and burden along with serum hormone/adipokine/myokine levels will be measured. Statistical analyses will be performed to identify relationships among genotypes, hormone/adipokine/myokine levels and rates of breast cancer initiation and progression.