HCV core protein modulates Rb pathway through pRb down-regulation and E2F-1 up-regulation

It has been recognized that the HCV (hepatitis C virus) core protein plays an important role in hepatocarcinogenesis. The functional inactivation of the Rb pathway appears to be a major event for multi-step cancer carcinogenesis. To elucidate the role of the HCV core protein in hepatocarcinogenesis,...

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Bibliographic Details
Published in:Biochimica et biophysica acta 2001-02, Vol.1538 (1), p.59-66
Main Authors: Cho, Jae-We, Baek, Won-Ki, Yang, Se-Hwan, Chang, Jun, Sung, Young Chul, Suh, Min-Ho
Format: Article
Language:English
Subjects:
Animals
Carcinoma, Hepatocellular - etiology
Carrier Proteins
Cell Cycle Proteins
Cell Line
Cell Survival
Core protein
DNA-Binding Proteins
Down-Regulation
Doxycycline - pharmacology
E2F Transcription Factors
E2F1 Transcription Factor
Genes, Retinoblastoma
Hepatitis C virus
Hepatocarcinogenesis
Liver Neoplasms - etiology
Microscopy, Phase-Contrast
Plasmids
Rats
Rb pathway
Retinoblastoma Protein - analysis
Retinoblastoma Protein - genetics
Retinoblastoma Protein - metabolism
Retinoblastoma-Binding Protein 1
RNA, Messenger - analysis
RNA, Messenger - metabolism
Transcription Factor DP1
Transcription Factors - analysis
Transcription Factors - genetics
Transcription Factors - metabolism
Transfection
Viral Core Proteins - biosynthesis
Viral Core Proteins - genetics
Viral Core Proteins - metabolism
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Summary:It has been recognized that the HCV (hepatitis C virus) core protein plays an important role in hepatocarcinogenesis. The functional inactivation of the Rb pathway appears to be a major event for multi-step cancer carcinogenesis. To elucidate the role of the HCV core protein in hepatocarcinogenesis, we investigated the effect of the HCV core protein on the Rb pathway in both Rat-1 cell lines, stably expressing the HCV core protein and the doxycycline-regulated cell lines. The HCV core stable transfectants showed a dramatic decrease in the pRb levels and E2F-1 up-regulation. In the doxycycline-regulated cell lines, the pRb levels were significantly decreased which are followed by E2F-1 up-regulation. HCV core stable transfectants showed higher cell growth rates and were sensitize to apoptosis. Thus, our results first indicate that the HCV core protein decreases the expression of pRb, thereby allowing E2F-1 to be constitutively active, which is thought to result in rapid cell proliferation or sensitizing to apoptosis.
ISSN:0167-4889
0006-3002
1879-2596
DOI:10.1016/S0167-4889(00)00137-3