P21WAF1/CIP1 messenger RNA expression in hepatitis B, C virus-infected human hepatocellular carcinoma tissues.
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.
Kobayashi
S
S
Second Department of Surgery, Chiba University School of Medicine, Chuoh-ku, Chiba, Japan. kobasi@med.m.chiba-u.ac.jp
Matsushita
K
K
Saigo
K
K
Urashima
T
T
Asano
T
T
Hayashi
H
H
Ochiai
T
T
D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000821:virology*; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000032:analysis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016174:Hepacivirus / Q000472:pathogenicity*; D006509:Hepatitis B / Q000150:complications*; D006515:Hepatitis B virus / Q000472:pathogenicity*; D006526:Hepatitis C / Q000150:complications*; D022781:Hepatocytes; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis*; D015854:Up-Regulation
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D012333:RNA, Messenger