Abstract:
BACKGROUND:The hepatitis B virus x gene (HBx) is a promiscuous transactivator implicated in the development of hepatocellular carcinoma (HCC). The present study was designed to investigate the molecular events regulated by HBx. METHODS:Genomic and proteomic expression profiling was performed in Huh7 HCC cells transfected with HBx mutants with a C-terminal deletion. The gene and protein expression of wingless-type murine-mammary-tumour virus (MMTV) integration site family, member 5A (Wnt-5a) was validated by analyses of reverse transcription-polymerase chain reaction (RT-PCR), real-time RT-PCR, western blot and immunohistochemistry. RESULTS:Differentially expressed genes and proteins were found in the transfected Huh7 HCC cells; most of them were involved in transcriptional regulation, although others including oncogenes or tumor suppressor genes, and molecules involved in cell junctions, signal transduction pathways, metabolism or the immune response were also observed. The expression of the Wnt-5a gene was elevated >10-fold in Huh7 cells transfected with the HBx3'-30 amino acid deletion mutant. However, the expression was downregulated by the transfection with the HBx3'-40 amino acid deletion mutant. The changes in Wnt-5a expression were also observed in human HCC tissues, compared with corresponding non-cancerous liver tissues. A negative correlation was found between the expression of Wnt-5a and HBx COOH mutations in HCC tissues. CONCLUSIONS:HBx mutants may participate in the development and progression of HCC, at least in part through the Wnt-5a pathway.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Liu X,Wang L,Zhang S,Lin J,Zhang S,Feitelson MA,Gao H,Zhu Mdoi
10.1093/carcin/bgn111subject
Has Abstractpub_date
2008-06-01 00:00:00pages
1207-14issue
6eissn
0143-3334issn
1460-2180pii
bgn111journal_volume
29pub_type
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