Alteration in gene expression profile by full-length hepatitis B virus genome.
Persistent expression of hepatitis B virus (HBV) proteins is thought to be involved in virus-related hepatocarcinogenesis. Here, we compared the gene expression profile of cells persistently expressing the full-length HBV with that of negative control cells to comprehensively investigate virus-mediated changes in the gene expression of the host cells. RNA samples from both virus-expressing and negative control cells were used for the DNA array assay. DNA array assay and subsequent corroboration assays revealed that expression of 14 of 1,176 genes (1.2%) was altered in response to virus expression. The upregulated genes included CD44, high mobility group protein-I, thymosin beta-10 and 27-kD heat shock protein, while the downregulated genes included NM23-H1, all of which are thought to be associated with the development or progression of carcinoma in the liver or other organs. Furthermore, virus expression resulted in the decrease of two apoptosis-inducing molecules, caspase-3 and BAX, which may also contribute to carcinogenesis through prolonged survival of the host cell. Thus, expression of the virus genome caused carcinogenesis-related changes in host cell gene expression. HBV expression may change the host cell to a malignant phenotype through alterations in the expression levels of a set of genes.
Nakanishi
Fumihiko
F
Department of Internal Medicine and Therapeutic, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Ohkawa
Kazuyoshi
K
Ishida
Hisashi
H
Hosui
Atsushi
A
Sato
Aki
A
Hiramatsu
Naoki
N
Ueda
Keiji
K
Takehara
Tetsuo
T
Kasahara
Akinori
A
Sasaki
Yutaka
Y
Hori
Masatsugu
M
Hayashi
Norio
N
D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000235:genetics; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016679:Genome, Viral; D025741:HMGA1a Protein / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013947:Thymosin / Q000235:genetics; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D004279:DNA, Viral; D006360:Heat-Shock Proteins; D018960:Hyaluronan Receptors; D054778:NM23 Nucleoside Diphosphate Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D025741:HMGA1a Protein; D013947:Thymosin; C039302:thymosin beta(10); C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases