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Differentially expressed genes associated with hepatitis B virus HBx and MHBs protein function in hepatocellular carcinoma.
Methods Mol Biol. 2006; 317:141-55.MM

Abstract

HBx and MHBst products from hepatitis B virus-DNA (HBV-DNA), which become transcriptional transactivators of cellular and viral genes, are known to play causative roles in the development of hepatocellular carcinoma (HCC). However, the biomolecular mechanism(s) for their roles in hepatocarcinogenesis in vivo remain poorly understood. To identify authentic cellular genes involved in HBx and MHBst-transactivated carcinogenesis,we used mRNA differential display polymerase chain reaction (DD-PCR). We examined HBx and MHBs-positive or -negative HCC, which had chromosomally integrated HBV DNA, vs nontumor tissues, respectively, and differentially expressed genes in either type of HCC were identified and compared with each other. Using 240 different combinations of three one-base anchored oligo-dT primers and 80 arbitrary 13mers, 16 genes were differentially expressed in the HBx and MHBs-positive HCC including RoRNA hY1, glutamine synthetase, factor H homologue 3' end, voltage-dependent anionc hannel 3 (VDAC3), three ribosomal proteins, four mitochondrial genes, and four novel genes. Unexpectedly, upregulated genes in association with functional HBV proteins were different from those reportedly transactivated by HBV viral proteins in vitro. Ten genes were downregulated, including three novel genes. In contrast, 15 genes in HCC tissue negative for HBx and MHBs-expression were preferentially expressed including pancreatic secretory trypsin inhibitor (PSTI), H19, guanidine nucleotide-binding protein alpha-1 subunit (GNAZ), carbamyl phosphate synthetase I (CPS I), insulin-like growth factor (IGF)-II, and 10 ribosomal proteins genes. Eighteen genes were downregulated including acute phase genes, a novel gene, and particularly the retinoblastoma susceptibility gene. Only two genes (ribosomal protein P0 and L37a) were commonly upregulated in both types of HCC tissues. These results suggest that cellular genes involved in the viral protein-transactivation may generally differ from those not associated with transactivation in established HCC, and that the specific oncogenic coordination through the transactivation by viral proteins which works in experiments in vitro, may play only a potential role in hepatocarcinogenesis in vivo. In addition, the functional analyses of the eight novel genes identified in this study might be valuable to further understand the mechanism(s) of hepatocarcinogenesis.

Authors+Show Affiliations

Division of GI and Hepatology, Department of Internal Medicine, Chonbuk National University Medical School and Hospital, Jeonbuk, Republic of Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16264227

Citation

Kim, Dae-Ghon. "Differentially Expressed Genes Associated With Hepatitis B Virus HBx and MHBs Protein Function in Hepatocellular Carcinoma." Methods in Molecular Biology (Clifton, N.J.), vol. 317, 2006, pp. 141-55.
Kim DG. Differentially expressed genes associated with hepatitis B virus HBx and MHBs protein function in hepatocellular carcinoma. Methods Mol Biol. 2006;317:141-55.
Kim, D. G. (2006). Differentially expressed genes associated with hepatitis B virus HBx and MHBs protein function in hepatocellular carcinoma. Methods in Molecular Biology (Clifton, N.J.), 317, 141-55.
Kim DG. Differentially Expressed Genes Associated With Hepatitis B Virus HBx and MHBs Protein Function in Hepatocellular Carcinoma. Methods Mol Biol. 2006;317:141-55. PubMed PMID: 16264227.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differentially expressed genes associated with hepatitis B virus HBx and MHBs protein function in hepatocellular carcinoma. A1 - Kim,Dae-Ghon, PY - 2005/11/3/pubmed PY - 2006/4/6/medline PY - 2005/11/3/entrez SP - 141 EP - 55 JF - Methods in molecular biology (Clifton, N.J.) JO - Methods Mol. Biol. VL - 317 N2 - HBx and MHBst products from hepatitis B virus-DNA (HBV-DNA), which become transcriptional transactivators of cellular and viral genes, are known to play causative roles in the development of hepatocellular carcinoma (HCC). However, the biomolecular mechanism(s) for their roles in hepatocarcinogenesis in vivo remain poorly understood. To identify authentic cellular genes involved in HBx and MHBst-transactivated carcinogenesis,we used mRNA differential display polymerase chain reaction (DD-PCR). We examined HBx and MHBs-positive or -negative HCC, which had chromosomally integrated HBV DNA, vs nontumor tissues, respectively, and differentially expressed genes in either type of HCC were identified and compared with each other. Using 240 different combinations of three one-base anchored oligo-dT primers and 80 arbitrary 13mers, 16 genes were differentially expressed in the HBx and MHBs-positive HCC including RoRNA hY1, glutamine synthetase, factor H homologue 3' end, voltage-dependent anionc hannel 3 (VDAC3), three ribosomal proteins, four mitochondrial genes, and four novel genes. Unexpectedly, upregulated genes in association with functional HBV proteins were different from those reportedly transactivated by HBV viral proteins in vitro. Ten genes were downregulated, including three novel genes. In contrast, 15 genes in HCC tissue negative for HBx and MHBs-expression were preferentially expressed including pancreatic secretory trypsin inhibitor (PSTI), H19, guanidine nucleotide-binding protein alpha-1 subunit (GNAZ), carbamyl phosphate synthetase I (CPS I), insulin-like growth factor (IGF)-II, and 10 ribosomal proteins genes. Eighteen genes were downregulated including acute phase genes, a novel gene, and particularly the retinoblastoma susceptibility gene. Only two genes (ribosomal protein P0 and L37a) were commonly upregulated in both types of HCC tissues. These results suggest that cellular genes involved in the viral protein-transactivation may generally differ from those not associated with transactivation in established HCC, and that the specific oncogenic coordination through the transactivation by viral proteins which works in experiments in vitro, may play only a potential role in hepatocarcinogenesis in vivo. In addition, the functional analyses of the eight novel genes identified in this study might be valuable to further understand the mechanism(s) of hepatocarcinogenesis. SN - 1064-3745 UR - https://www.unboundmedicine.com/medline/citation/16264227/Differentially_expressed_genes_associated_with_hepatitis_B_virus_HBx_and_MHBs_protein_function_in_hepatocellular_carcinoma_ L2 - https://dx.doi.org/10.1385/1-59259-968-0:141 DB - PRIME DP - Unbound Medicine ER -