Protein kinase R is increased and is functional in hepatitis C virus—related hepatocellular carcinoma

Hiasa, Yoichi; Kamegaya, Yoshitaka; Nuriya, Hideko; Onji, Morikazu; Kohara, Michinori; Schmidt, Emmett V.; Chung, Raymond T.
November 2003
American Journal of Gastroenterology;Nov2003, Vol. 98 Issue 11, p2528
Academic Journal
: ObjectiveProtein kinase R (PKR) interacts with dsRNA and phosphorylates eukaryotic initiation factor-2 (eIF2α), which in turn inhibits host translation initiation as well as hepatitis C virus (HCV) translation. Because PKR inhibits host cell growth and proliferation, it has also been proposed to act as a eukaryotic tumor suppressor. To evaluate the role of PKR in HCV-related hepatocellular carcinoma (HCC), we compared PKR and related protein expression in paired tumor (T) and surrounding nontumor (NT) tissue.: MethodsTissue samples were obtained from 12 HCV-infected HCCs. To determine PKR and related protein expression, Western blotting and semiquantitative reverse transcriptase–polymerase chain reaction were performed.: ResultsPKR protein levels were consistently increased in HCV-related HCC compared with NT (p = 0.001); similar increases were seen in total eIF2α and the PKR inhibitor p58IPK in T compared with NT (p = 0.022, p = 0.048, respectively). Relative increases in phosphorylated eIF2α (peIF2α) were also seen, and the ratio of peIF2α/total eIF2α did not change in T compared with NT, suggesting that PKR remains functional within T. Cytoplasmic levels of HCV RNA within T were decreased compared with NT.: ConclusionsThese findings indicate that PKR has increased activity in human HCC compared with LC, and suggest that PKR acts as a growth inducer in HCC.


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