HEPATITIS C VIRUS AND HEPATOCELLULAR CARCINOMA | ||
| The Egyptian Science Magazine | ||
| Volume 1, Issue 1, December 2004, Pages 1-12 PDF (3.93 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/esm.2004.467137 | ||
| Authors | ||
| ABDEL-RAHMAN N. ZEKRI* 1; ABEER A. BAHNASSY* 2; HUSSEIN M. KHALED* 3; MAHMOUD M. EL-MERZABANI* 4 | ||
| 1Virology and Immunology Unit Cancer Biology Department *Corresponding author: Cancer Biology Department. National Cancer Institute. Fam El-Khalig, Cairo 11796, Egypt E-mail: neizabri@starnet.com.eg Abbreviations: MMR – mismatch repair; FHIT – fragile histidine triad; p53– oncosuppressor gene; C-erb B2– protein receptor with tyrosine kinase activity similar to epidermal growth factor receptor; MDM-2 – one of the apoptosis regulating proteins; p21-Waf – cyclin dependent kinase inhibitor (involved in cell cycle regulation; p21 Ras – oncogene; NS3 – nonstructural 3 protein coded by HCV | ||
| 2Tissue culture Unit, Pathology Department | ||
| 3Medical Oncology Department National Cancer Institute | ||
| 4Pharmacology Unit, Cancer Biology Department | ||
| Abstract | ||
| Different etiological factors such as hepatitis viral infection, alcohol, aflatoxin and chemical carcinogens were mentioned in relation to HCC. However, the global distribution of HCC is strongly linked to the prevalence of hepatitis virus infection. The exact pathogenic mechanisms involved in viral-associated HCC are unclear although direct and indirect mechanisms are possible. Direct carcinogenicity is less certain in HCV-Induced HCC since it is a typical RNA virus and therefore the integration of viral genome into host cell chromosomes has not been shown to occur. However, the presence of two conserved potential nuclear localization signals and a DNA binding motif in the HCV core protein suggest a possible functional role as a regulatory element. Moreover, some studies demonstrated that this protein interacts with certain cellular proto-oncogenes at the transcriptional level, resulting in the promotion of cell proliferation and thus affecting normal hepatocyte growth. Therefore the pathogenesis of HCC may be attributed at least in part to the upregulation of hepatocyte growth induced by HCV core protein and other viral proteins like NS3 and NS5. However, the process of malignant transformation represents a dynamic interplay between classes of genes; oncogenes, tumor suppressor genes, mismatch repair genes, genes controlling apoptosis and cell cycle regulatory genes. In conclusion, since the exact mechanism of action of HCV in the context of HCC is still poorly understood, clarification of the molecular basis of viral replication in hepatocytes, the possible genetic and cytogenetic abnormalities that may be induced by the virus were emphasized in this review. Moreover, early detection of hepatocellular changes by molecular biomarkers may help to detect individuals at high risk of development HCC, thus allowing more effective intervention for cure or prevention. | ||
| Keywords | ||
| HCC; HCV; MMR; FHIT; p53; C-erb-B2; MDM-2; p21waf; p21Ras; NS3; apoptosis | ||
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