Journal
BRITISH JOURNAL OF CANCER
Volume 98, Issue 2, Pages 443-449Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6604150
Keywords
muscle atrophy; cancer patients; PKR; eIF2 alpha; p70(S6k)
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Previous studies suggest that the activation ( autophosphorylation) of dsRNA-dependent protein kinase (PKR) can stimulate protein degradation, and depress protein synthesis in skeletal muscle through phosphorylation of the translation initiation factor 2 (eIF2) on the a-subunit. To understand whether these mediators are important in muscle wasting in cancer patients, levels of the phospho forms of PKR and eIF2 alpha have been determined in rectus abdominus muscle of weight losing patients with oesophago-gastric cancer, in comparison with healthy controls. Levels of both phospho PKR and phospho eIF2a were significantly enhanced in muscle of cancer patients with weight loss irrespective of the amount and there was a linear relationship between phosphorylation of PKR and phosphorylation of eIF2 alpha ( correlation coefficient 0.76, P = 0.005). This suggests that phosphorylation of PKR led to phosphorylation of eIF2 alpha. Myosin levels decreased as the weight loss increased, and there was a linear relationship between myosin expression and the extent of phosphorylation of eIF2 alpha ( correlation coefficient 0.77, P = 0.004). These results suggest that phosphorylation of PKR may be an important initiator of muscle wasting in cancer patients.
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