COBRE: USC: EXERCISE AND POLYPOSIS IN THE APCMIN/+ MOUSE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have made significant progress over the past 12 months expanding on preliminary data related to skeletal muscle mass loss with cancer cachexia in the ApcMIn/+ mouse. Our plans related to this project will focus on further data generation, new grant development, and manuscript preparation and submission. 1) We will resubmit the revised grant titled ¿Cachexia in ApcMIn/+ mice: the role of IL-6¿ to the NCI on July 1 2006. Although the initial submission was not scored, the reviews were positive and indicated strong potential. Additional pilot data have been collected, the grant is better focused, and the roles of co-PIs have been broadened to provide deeper experience. The experiments in the proposal are designed to mechanistically extend our preliminary data demonstrating the potential for IL-6 regulation of cachexia in the ApcMin/+ mouse. The specific aims in the proposal will use both in vivo functional tests, biochemical analysis, and morphological examination to prove the working hypothesis that a chronically inflamed state that elevates circulating IL-6 both initiates and promotes muscle wasting by fiber-type specific mechanisms. We will continue to collect data over the next year on experiments outlined in the grant proposal. 2) Other projects: A second grant is being formulated that would examine IL-6 regulation of adipose tissue loss due to the induction of uncoupling proteins in skeletal muscle. An additional grant idea related to other work in the lab is the role of the androgen receptor in the process of muscle wasting. The cardiac hypertrophy in the cachectic mouse is also being examined by a Doctoral Dissertation and with collaborators at the USC Medical School. 3) Productivity: We will finish 2 cachexia-related manuscripts that are currently in preparation and will be pushed towards submission and publication during 2006-2007. The first manuscript is focused on the role of IL-6 in ApcMin/+ mice. We will also be submitting 2 additional manuscripts currently in preparation that were COBRE- funded studies related to exercise, diet and chemoprevention in the ApcMin/+ mouse. 5) Cancer and exercise: A revision of the American Institute for Cancer Research grant submission will be submitted July 1 2006. The previous submission was 1 point from the funding line. This proposal will allow for continuation of the exercise, diet and chemoprevention studies in the ApcMin/+ mouse that were intitiated by COBRE funding.