In a healthy person, muscle mass is maintained by balancing the breakdown of muscle protein with the production of new cells and protein.  In 30% of cancer patients, this balance is lost and there is progressive loss of muscle mass, a condition known as cachexia.  The development of treatment and prevention strategies for cachexia is of utmost importance since this condition decreases patient survival and makes cancer therapies less effective.  It is theorized that cachexia is caused, at least in part, by factors produced by the tumour or by the patient’s immune system which act to destroy muscle.  In both cachectic cancer patients and animal models of cachexia, elevated levels of signalling molecules called proinflammatory cytokines have been observed, suggesting that these factors play a role in the development of cachexia in vivo. The proinflammatory cytokines act to increase muscle protein breakdown, which injures the muscle itself.  Normally, in a healthy individual, the muscle would be repaired through the development of new muscle cells.  Muscle regeneration happens through the increased expression of MyoD.  In cachexia, the expression of MyoD is prevented thereby inhibiting muscle regeneration.  We have discovered that CAAT/Enhancer Binding Protein beta (C/EBPbeta), a bzip transcription factor, is a potent repressor of MyoD expression in muscle.  We hypothesize that cachectic signals increase C/EBPbeta levels in muscle leading to inhibition of MyoD expression and crippled muscle regeneration.  The objectives of this project are:  (i) to correlate C/EBPb expression with muscle mass loss in an in vivo model of cancer cachexia; (ii) to assess the importance of C/EBPb expression for the development of cachexia.