The expression of genes in the ubiquitin-proteasome proteolytic pathway is increased in skeletal muscle from patients with cancer.

The intracellular mechanisms of muscle cachexia in patients with cancer are not known. To assess the role of the ubiquitin-proteasome proteolytic pathway in cancer-induced muscle breakdown, we determined messenger RNA levels for ubiquitin and several 20S proteasome subunits in muscle from patients undergoing surgery for cancer A biopsy specimen was obtained from the rectus abdominis muscle in patients undergoing laparotomy for cancer (n = 6) or noncancer disease (n = 6). Tissue levels of mRNA for ubiquitin and the 20S proteasome subunits HC3, HC5, HC7, and HC9 were determined by dot blot analysis. The mRNA levels for ubiquitin and the 20S proteasome subunits were 2 to 4 times higher in muscle from patients with cancer than in muscle from control patients. This is the first report of increased expression of genes in the ubiquitin-proteasome proteolytic pathway in muscle tissue from patients with cancer. Cancer-induced muscle catabolism may at least in part reflect ubiquitin-proteasome-dependent protein breakdown.