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Effects of Hepatitis B Virus X Protein (HBx) on Cell-Growth Inhibition in a CCL13-HBx Stable Cell Line

Chan-Yen Kuo, Jing-Chyi Wang, Cheng-Chung Wu, Shih-Lan Hsu, Guang-Yuh Hwang
2008 Intervirology  
Introduction The hepatitis B virus (HBV) is a member of the Hepadnaviridae family and a well-known risk factor in the development of human hepatocellular carcinoma (HCC) [22] . The HBV-encoded X protein (HBx) has been demonstrated to play a critical role in mediating the pathological effects of this virus [11, 21, 22] . HBx mediates cell growth, which includes cell death and cell survival, via proliferation and apoptosis [3] , and it is associated with signal transduction cascades [4] .
more » ... cades [4] . Currently, the signal pathways involving HBx include the ras/raf/MAPK [8] , PKB/Akt [16] , and JAK/STAT pathways [33] . Furthermore, the transcriptional factors involving HBx include NF-B, AP-1, CREB/ATF [34] , RNA polymerase subunit RBP5 [7] , and TBP [ 1, 11, 24] . Although the contribution of HBx to the development of HCC via transcriptional activation and signal alteration has been demonstrated, the critical role played by HBx in hepatocarcinogenesis remains unclear. Recently, ␤ -catenin mutation and accu-Abstract Objective: The known function of hepatitis B virus X protein (HBx) is to determine the fate of cells by modulating various signaling pathways. In our previous study, we demonstrated that HBx inhibits tumor formation in nude mice injected with CCL13-HBx stable cell lines; however, the mechanism underlying this inhibition is unclear. Methods: To investigate the possible mechanisms underlying HBx involvement in CCL13-HBx cells, gene profiles were initially analyzed by DNA microarray technology and subsequently confirmed by performing semiquantitative RT-PCR and Western blotting. Furthermore, the phenomenon of cell death via apoptosis was detected via DNA fragmentation, TUNEL staining, caspase-3 activity assay, and propidium iodide (PI) staining. Results: The results indicated that HBx induction downregulated Wnt-3 and ␤ -catenin that are involved in cell proliferation. Moreover, HBx induction repressed cell growth and downregulated the expressions of cyclin D1, CDK4, cyclin E, CDK2, and cyclin B1. Furthermore, HBx induction triggered cell death via apoptosis, as determined by DNA fragmentation, TUNEL staining, caspase-3 activity assay, and PI staining.
doi:10.1159/000118793 pmid:18309246 fatcat:t42wbfvzevdnpmv6eraymhwsji