hcv tumor promoting effect is dependent on host genetic background丙肝病毒肿瘤促进作用依赖于宿主遗传背景.pdfVIP

HCV Tumor Promoting Effect Is Dependent on Host Genetic Background 1 2 3 4 1 Naama Klopstock , Mark Katzenellenbogen , Orit Pappo , Miriam Sklair-Levy , Devorah Olam , Lina 1 1 1 1 Mizrahi , Tamara Potikha , Eithan Galun , Daniel Goldenberg * 1 Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel, 2 Bioinformatics and Microarray Unit, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel, 3 Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel, 4 Breast Imaging Center, Sheba Medical Center, Tel Hashomer, Israel Abstract Background: The hepatitis C virus (HCV) is one of the major risk factors for the development of hepatocellular carcinoma (HCC). Nevertheless, transgenic mice which express the whole HCV polyprotein (HCV-Tg) do not develop HCC. Whereas chronic HCV infection causes inflammation in patients, in HCV-Tg mice, the host immune reaction against viral proteins is lacking. We aimed to test the role of HCV proteins in HCC development on the background of chronic inflammation in vivo. Methodology/Principal Findings: We crossed HCV-Tg mice that do not develop HCC with the Mdr2-knockout (Mdr2-KO) mice which develop inflammation-associated HCC, to generate Mdr2-KO/HCV-Tg mice. We studied the effect of the HCV transgene on tumor incidence, hepatocyte mitosis and apoptosis, and investigated the potential contributing factors for the generated phenotype by gene expression and protein analyses. The Mdr2-KO/HCV-Tg females from the N2 generation of this breeding (having 75% of the FVB/N genome and 25% of the C57BL/6 gen