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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Protein kinase R is increased and is functional in hepatitis C virus-related hepatocellular carcinoma

Yoichi Hiasa1, Yoshitaka Kamegaya, Hideko Nuriya

  • 1Gastrointestinal Unit, Cancer Center and Hospital for Children, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

The American Journal of Gastroenterology
|November 26, 2003
PubMed
Abstract

Insights

Protein kinase R (PKR) is elevated in hepatitis C virus (HCV)-related liver cancer (HCC), contradicting its proposed tumor suppressor role. Findings suggest PKR promotes tumor growth in HCC.

Area of Science:

  • Molecular biology
  • Oncology
  • Virology

Background:

  • Protein kinase R (PKR) phosphorylates eukaryotic initiation factor-2 alpha (eIF2alpha), inhibiting translation.
  • PKR's proposed tumor suppressor role stems from its inhibition of host cell growth.
  • The role of PKR in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) remains unclear.

Purpose of the Study:

  • To investigate the expression and activity of PKR in HCV-related HCC.
  • To compare PKR and related protein levels in tumor (T) versus nontumor (NT) tissues from HCC patients.

Main Methods:

  • Western blotting and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) were used.
  • Tissue samples were analyzed from 12 patients with HCV-infected HCC.
  • Expression levels of PKR, eIF2alpha, phosphorylated eIF2alpha (peIF2alpha), and p58IPK were quantified.

Main Results:

  • PKR protein levels were significantly increased in HCC tumor tissues compared to nontumor tissues (p=0.001).
  • Elevated levels of total eIF2alpha and the PKR inhibitor p58IPK were also observed in tumor tissues.
  • Increased peIF2alpha indicated functional PKR, while decreased HCV RNA in tumors suggested altered viral-host interactions.

Conclusions:

  • PKR exhibits increased activity in human HCC compared to normal liver (LC).
  • These findings challenge the tumor suppressor hypothesis, suggesting PKR acts as a growth inducer in HCC.
  • Further research is needed to elucidate PKR's complex role in liver cancer progression.

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