Reduction of double-stranded RNA-activated protein kinase in hepatocellular carcinoma associated with hepatitis B virus.
Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) in Asia. Double-stranded RNA (dsRNA)-activated protein kinase (PKR) is an interferon-induced, serine/threonine protein kinase. Recent studies have suggested that PKR is involved in the pathogenesis of HCC with hepatitis virus C infection by inhibiting viral and cellular proteins related to cell growth and proliferation. In the present study, PKR was examined in both tumor and non-tumor tissues from HCC livers infected with HBV. The expression of PKR was determined by TaqMan real-time PCR and immunohistochemical methods. The level of PKR was also analyzed in relation to pathological changes observed in HCC. The result showed that PKR was reduced in tumor tissues of HCC from HBV carriers with low serum viral load (<0.7 x 10(6) copies/ml) compared to those with higher serum viral load. However, the overall PKR level was much lower in tumor tissues than that in non-tumor tissues, irrespective of HBV carrier status or serum viral load. PKR level tended to be lower in HCC samples with alpha-fetoprotein (AFP) more than 500 ng/ml (mean: 4024.2 ng/ml) than those with AFP less than 500 ng/ml (mean: 50.6 ng/ml). There was no significant difference in the expression of PKR between tumor tissues with well differentiation and those with poor or moderate differentiation. In conclusion, the level of PKR was reduced in HCC tumor tissues, suggesting a possible role of PKR in promoting the growth of tumor. HBV may participate in altering the level of PKR, but factors other than HBV should play a more determining role in the regulation of PKR in HCC. The association between PKR and AFP levels may offer an alternative tumor marker for HCC.
Chen
George G
GG
Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T. Hong Kong. gchen@cuhk.edu.hk
Lai
Paul B S
PB
Ho
Rocky L K
RL
Chan
Paul K S
PK
Xu
H
H
Wong
John
J
Lau
Wan Y
WY
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000097:blood / Q000302:isolation & purification; D005260:Female; D015870:Gene Expression; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000302:isolation & purification; D019562:Viral Load; D000509:alpha-Fetoproteins / Q000032:analysis; D019892:eIF-2 Kinase / Q000096:biosynthesis* / Q000235:genetics*
D014408:Biomarkers, Tumor; D004279:DNA, Viral; D012333:RNA, Messenger; D000509:alpha-Fetoproteins; D019892:eIF-2 Kinase