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, 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.
Cho
J
J
Department of Microbiology, College of Medicine, Seonam University, Namwon, South Korea.
Baek
W
W
Yang
S
S
Chang
J
J
Sung
Y C
YC
Suh
M
M
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D002470:Cell Survival; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D004318:Doxycycline / Q000494:pharmacology; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016161:Genes, Retinoblastoma; D008113:Liver Neoplasms / Q000209:etiology; D008858:Microscopy, Phase-Contrast; D010957:Plasmids; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D016160:Retinoblastoma Protein / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493755:E2f1 protein, rat; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D004318:Doxycycline