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Open Access Research

Implication of protein kinase R Gene quantification in hepatitis C Virus Genotype 4 induced Hepatocarcinogenesis

Amal A Mohamed1, Ola H Nada24* and Mohamed A El Desouky3

Author Affiliations

1 Department of Biochemistry, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt

2 Department of Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

3 Department of Biochemistry, Faculty of Science, Cairo University, Cairo, Egypt

4 Ain Shams University-Faculty of medicine-Pathology department-Abbassia, Cairo, Egypt

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Diagnostic Pathology 2012, 7:103  doi:10.1186/1746-1596-7-103

Published: 15 August 2012

Abstract

Background

Protein kinase RNA (PKR-regulated) is a double-stranded RNA activated protein kinase whose expression is induced by interferon. The role of PKR in cell growth regulation is controversial, with some studies supporting a tumour suppressor function and others suggesting a growth-promoting role. However, it is possible that the function of PKR varies with the type of cancer in question.

Methods

We report here a detailed study to evaluate the function of PKR in hepatitis C virus genotype 4 (HCV-4) infected patients. PKR gene was quantitated in HCV related malignant and non-malignant liver tissue by RT-PCR technique and the association of HCV core and PKR was assessed.

Results

If PKR functions as a tumour suppressor in this system, its expression would be higher in chronic hepatitis tissues. On the contrary our study demonstrated the specific association of HCV-4 with PKR expressed in hepatocellular carcinoma (HCC) tissues, leading to an increased gene expression of the kinase in comparison to chronic hepatitis tissues. This calls into question its role as a tumour suppressor and suggests a positive regulatory role of PKR in growth control of liver cancer cells. One limitation of most of other studies is that they measure the levels rather than the quantitation of PKR gene.

Conclusion

The findings suggest that PKR exerts a positive role in cell growth control of HCV-4 related HCC, obtaining a cut-off value for PKR expression in liver tissue provides the first evidence for existence of a viral activator of PKR.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1267826959682402.

Keywords:
Genotype 4 HCV; Hepatocellular carcinoma; Liver; PKR