BACKGROUND: 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 METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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 METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Jie Du; Xiaonan Wang; Christiane Miereles; James L Bailey; Richard Debigare; Bin Zheng; S Russ Price; William E Mitch Journal: J Clin Invest Date: 2004-01 Impact factor: 14.808
Authors: I Dahlman; N Mejhert; K Linder; T Agustsson; D M Mutch; A Kulyte; B Isaksson; J Permert; N Petrovic; J Nedergaard; E Sjölin; D Brodin; K Clement; K Dahlman-Wright; M Rydén; P Arner Journal: Br J Cancer Date: 2010-04-20 Impact factor: 7.640