Department of Biochemistry, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.
Diagn Pathol. 2012 Aug 15;7:103. doi: 10.1186/1746-1596-7-103.
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.
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.
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.
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.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1267826959682402.
蛋白激酶 RNA（PKR 调节）是一种双链 RNA 激活的蛋白激酶，其表达受干扰素诱导。PKR 在细胞生长调节中的作用存在争议，一些研究支持其作为肿瘤抑制因子的功能，而另一些研究则表明其具有促进生长的作用。然而，PKR 的功能可能因所研究的癌症类型而异。
我们在此报告了一项详细的研究，以评估丙型肝炎病毒基因型 4（HCV-4）感染患者中 PKR 的功能。通过 RT-PCR 技术定量检测 HCV 相关恶性和非恶性肝组织中的 PKR 基因，并评估 HCV 核心蛋白与 PKR 的相关性。
如果 PKR 在该系统中作为肿瘤抑制因子发挥作用，其在慢性肝炎组织中的表达应该更高。然而，我们的研究表明，HCV-4 与在肝细胞癌（HCC）组织中表达的 PKR 特异性相关，导致激酶基因的表达增加，与慢性肝炎组织相比。这使人对其作为肿瘤抑制因子的作用产生质疑，并表明 PKR 在肝癌细胞生长控制中具有正向调节作用。大多数其他研究的一个局限性是它们测量的是 PKR 基因的水平而不是定量。
这些发现表明，PKR 在 HCV-4 相关 HCC 的细胞生长控制中发挥积极作用，在肝组织中获得 PKR 表达的截止值为 PKR 的存在提供了第一个病毒激活剂的证据。
本文的虚拟幻灯片可以在此处找到：http://www.diagnosticpathology.diagnomx.eu/vs/1267826959682402.
