SAGE transcript profiles of normal primary human hepatocytes expressing oncogenic hepatitis B virus X protein.
Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). HBV encodes an oncogenic HBx gene that functions as a transcriptional coactivator of multiple cellular genes. To understand the role(s) of HBx in the early genesis of HCC, we systematically analyzed gene expression profiles by serial analysis of gene expression (SAGE) in freshly isolated human primary hepatocytes infected with a replication-defective adenovirus containing HBx. A total of 19,501 sequence tags (representing 1443 unique transcripts) were analyzed, which provide a distribution of a transcriptome characteristic of normal hepatocytes and a profile associated with HBx expression. Examples of the targeted genes were confirmed by the Megarray analysis with a significant correlation between quantitative SAGE and Megarray (r = 0.8, P < 0.005). In HBx-expressing hepatocytes, a total of 57 transcripts (3.9%) were induced, and 46 transcripts (3.3%) were repressed by more than fivefold. Interestingly, most of the HBx-up-regulated transcripts can be clustered into three major classes, including genes that encode ribosomal proteins, transcription factors with zinc-finger motifs, and proteins associated with protein degradation pathways. These results suggest that HBx may function as a major regulator in common cellular pathways that, in turn, regulate protein synthesis, gene transcription, and protein degradation.
Wu
Chuan-Ging
CG
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA.
Forgues
Marshonna
M
Siddique
Shabina
S
Farnsworth
Julie
J
Valerie
Kristoffer
K
Wang
Xin Wei
XW
D000256:Adenoviridae / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D009693:Nucleic Acid Hybridization / Q000379:methods; D014176:Protein Biosynthesis / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
D011506:Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein