OBJECTIVE: Protein kinase R (PKR) interacts with dsRNA and phosphorylates eukaryotic initiation factor-2 (eIF2alpha), 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. METHODS: Tissue 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. RESULTS: PKR protein levels were consistently increased in HCV-related HCC compared with NT (p=0.001); similar increases were seen in total eIF2alpha and the PKR inhibitor p58IPK in T compared with NT (p=0.022, p=0.048, respectively). Relative increases in phosphorylated eIF2alpha (peIF2alpha) were also seen, and the ratio of peIF2alpha/total eIF2alpha 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. CONCLUSIONS: These findings indicate that PKR has increased activity in human HCC compared with LC, and suggest that PKR acts as a growth inducer in HCC.
OBJECTIVE: Protein kinase R (PKR) interacts with dsRNA and phosphorylates eukaryotic initiation factor-2 (eIF2alpha), 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. METHODS: Tissue 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. RESULTS:PKR protein levels were consistently increased in HCV-related HCC compared with NT (p=0.001); similar increases were seen in total eIF2alpha and the PKR inhibitor p58IPK in T compared with NT (p=0.022, p=0.048, respectively). Relative increases in phosphorylated eIF2alpha (peIF2alpha) were also seen, and the ratio of peIF2alpha/total eIF2alpha 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. CONCLUSIONS: These findings indicate that PKR has increased activity in human HCC compared with LC, and suggest that PKR acts as a growth inducer in HCC.
Authors: Xiaodong Cheng; Michael Byrne; Kevin D Brown; Marina Y Konopleva; Steven M Kornblau; Richard L Bennett; W Stratford May Journal: Blood Date: 2015-07-22 Impact factor: 22.113
Authors: N Kunkeaw; S H Jeon; K Lee; B H Johnson; S Tanasanvimon; M Javle; C Pairojkul; Y Chamgramol; W Wongfieng; B Gong; C Leelayuwat; Y S Lee Journal: Oncogene Date: 2012-08-27 Impact factor: 9.867