Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2 alpha may signal skeletal muscle atrophy in weight-losing cancer patients

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Authors

  • H.L. Eley
  • R.J.E. Skipworth
  • D.A.C. Deans
  • K.C.H. Fearon
  • Michael J. Tisdale

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Abstract

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 alpha-subunit. To understand whether these mediators are important in muscle wasting in cancer patients, levels of the phospho forms of PKR and eIF2alpha 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 eIF2alpha 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 eIF2alpha (correlation coefficient 0.76, P=0.005). This suggests that phosphorylation of PKR led to phosphorylation of eIF2alpha. Myosin levels decreased as the weight loss increased, and there was a linear relationship between myosin expression and the extent of phosphorylation of eIF2alpha (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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  • Increased expression of phosphorylated forms of RNA-dependent protein

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Details

Original languageEnglish
Pages (from-to)443-449
Number of pages7
JournalBritish Journal of Cancer
Volume98
Issue number2
DOIs
Publication statusPublished - 29 Jan 2008

Bibliographic note

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

    Keywords

  • muscle atrophy, cancer patients, PKR, eIF2 alpha, p70(S6k)

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