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

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. Cancer 2001;91:2096–103. © 2001 American Cancer Society.

Identification of genes up-regulated by histone deacetylase inhibition with cDNA microarray and exploration of epigenetic alterations on hepatoma cells

“…The activation of p21 WAF1 induced by HDAC inhibitors results in the growth arrest by induction of G 1 arrest in several malignant cell lines [26,27]. Kobayashi et al documented the association between decreased expression levels of p21 WAF1 and hepatocarcinogenesis [28]. Both CYR61 and CTGF belong to CYR61/CTGF/ nephroblastoma-overexpressed family and affect extracellular matrix signaling [29].…”

Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis

“…Indeed, in mice, depletion of p21 leads to a continuous proliferation of severely injured hepatocytes and rapid tumor development [91]. In lines with this, p21/Waf1 expression levels in the cancerous tissues appear to be significantly reduced compared to those in the noncancerous tissues [224, 225]. Furthermore, the histological negativity for p21/Waf1 serves as a negative prognostic factor for the survival of patients with HCC after resection [226], although a contrary finding has also been reported [227].…”

Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model

“…Kobayashi et al . [43] reported that p21 mRNA expression in normal tissues is significantly higher in HCV-positive cases compared to HBV-positive cases. These data supports our findings that p21 protein expression was affected not only by fibrosis but also hepatitis virus type.…”