P21WAF1/CIP1 messenger RNA expression in hepatitis B, C virus-infected human hepatocellular carcinoma tissues

Cancer. 2001 Jun 1;91(11):2096-103. doi: 10.1002/1097-0142(20010601)91:11<2096::aid-cncr1237>3.0.co;2-9.

Abstract

Background: The primary objective of this study was to clarify the significance of p21WAF1/CIP1(p21) gene expression in the tumorgenicity of hepatitis B virus (HBV) and hepatitis C virus (HCV) infected human hepatocelluar carcinoma (HCC).

Methods: The authors performed Northern blot hybridization to compare the p21 messenger (m) RNA expression levels among 16 HCC cases. They detected tissue HBVx mRNA (Northern blot) and plus- and minus-strand HCV RNA (reverse transcription-polymerase chain reaction) in liver tissues. They also measured alanine transaminase (ALT) levels and indocyanine green retention rate at 15 minutes (ICG-R15).

Results: The p21 transcripts of tumor (T) tissues could be identified with lower intensity than nontumor (N) tissues in all 4 HBVx mRNA(+) cases, 8 of 10 HCV RNA(+) cases, and 1 of 3 B(-), C(-) cases (1 case was positive for both viruses). p21 mRNA expression levels of N tissues were significantly higher in HCV RNA(+) cases than in HBVx mRNA(+) cases. p21 mRNA expression levels of N tissues were significantly correlated with serum ALT levels.

Conclusions: In HCV hepatitis, p21 mRNA expression is up-regulated to control cell cycle under regeneration stress. Once the liver develops HCC, the p21 mRNA expression decreases to prominently low levels. The up-regulated p21 expression may play a role as a guard to prevent hepatocytes from tumorgenicity in HCV hepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blotting, Northern
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / virology*
  • Cell Cycle
  • Cell Transformation, Neoplastic
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / biosynthesis*
  • Enzyme Inhibitors / analysis*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Hepacivirus / pathogenicity*
  • Hepatitis B / complications*
  • Hepatitis B virus / pathogenicity*
  • Hepatitis C / complications*
  • Hepatocytes
  • Humans
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • RNA, Messenger / biosynthesis*
  • Up-Regulation

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Enzyme Inhibitors
  • RNA, Messenger