Furthermore, specimens from patients with HCC revealed a close relationship between ER stress and autophagy, as demonstrated by the high correlation between expression of the autophagy-associated protein Beclin1 and expression of unfolded protein response (UPR) pathway proteins, especially PKR-like ER stress kinase (PERK); moreover, patients with combined expression of PERK and Beclin1 had more advanced disease (higher clinical stage) and a shorter overall survival time.
Both the genetic and pharmacological inhibitions of PlGF reduced the chaperone levels and the activation of the PKR-like endoplasmic reticulum kinase (PERK) pathway of the UPR in diethylnitrosamine-induced HCC.
Double-stranded RNA-activated protein kinase R (PKR) is known to be upregulated by hepatitis C virus (HCV) and overexpressed in hepatocellular carcinoma (HCC).
On the contrary our study demonstrated the specific association of HCV-4 with PKR expressed in hepatocellular carcinoma (HCC) tissues, leading to an increased gene expression of the kinase in comparison to chronic hepatitis tissues.
The tumor suppressive effect of AdhTERT-E2F therapy was further enhanced in combination with IFNalpha.Our results demonstrate that PKR activating agents enhance the anti-tumor effect of E2F-1 overexpression in HCC in-vitro and in-vivo.
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).
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).