Modulation of cell death sensitivity by mutant p53 in HCV core-expressing cells.
The hepatitis C virus (HCV) core protein plays important roles in hepatocarcinogenesis through modulation of cellular proliferation, apoptosis, and immunological responses. The roles of core protein in apoptosis have been conflicting; both proapoptotic and anti-apoptotic roles have been reported from different experimental conditions. Nonetheless, the overcoming apoptosis is a key molecular event to development of hepatocellular carcinoma. We investigated whether the HCV core-expressing cells are susceptible to apoptosis after cellular stress. Furthermore, we focused on the possibility that the presence of mutant p53 can render cells resistant to apoptosis. Our data clearly indicated that core-expressing cells showed increased apoptotic cell death through caspase-3 activation pathways after genotoxic stress without modulation of Bcl-2 family proteins. However, core-expressing cells, when transiently transfected with mutant p53, showed markedly increased resistance upon apoptosis after genotoxic stress. Thus, our data suggest that even though HCV core-expressing cells are susceptible to apoptosis after genotoxic stress, cells are resistant to apoptosis under mutant p53, implying a functional abnormality of p53 giving a chance to overcome apoptosis and ultimately cells develop into hepatocellular cell carcinoma.
Cho
Jae-We
JW
Department of Microbiology, College of Medicine, Seonam University, Namwon, Chunpook 590-711, South Korea.
Park
Kun
K
Kweon
Gi Ryang
GR
Park
Jong-Chun
JC
Lee
Je-Chul
JC
Baek
Won-Ki
WK
Jang
Byeong-Churl
BC
Suh
Seong-Il
SI
Suh
Min-Ho
MH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D005047:Etoposide / Q000494:pharmacology; D016174:Hepacivirus / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D014758:Viral Core Proteins / Q000235:genetics* / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D014758:Viral Core Proteins; D005047:Etoposide; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases