Hepatitis C virus core protein induces apoptosis and impairs cell-cycle regulation in stably transformed Chinese hamster ovary cells

Hepatitis C virus (HCV) infection is associated with the development of hep atocellular carcinoma. Several lines of evidence suggest that the core prot ein of HCV may play a role in the development of this cancer. The authors e xamined regulation of the cell cycle in stable cell lines derived from Chin ese hamster ovary (CHO-K1) cells that constitutively expressed one or more of the structural proteins of HCV. In media containing low concentrations o f serum (serum starvation), cell lines expressing the core protein showed a significantly lower population of viable cells than noncore-expressing cel ls. The low viability of the core-expressing cells was a result of the incr eased population of cells undergoing apoptosis. Interestingly, the cell cyc le analysis revealed that the arresting function at G(0) was impaired, and the cell cycle was accelerated in core-expressing cell lines even under ser um starvation. Thus, the HCV core protein sensitizes the apoptosis to serum starvation, although it promotes the cell cycle in CHO-K1 cells. To explai n these findings, the authors examined the expression of revival apoptosis and cell-cycle-related genes. Expression of the c-myc genes was significant ly induced in core-expressing cells in response to serum starvation. Other apoptosis-inducing genes downstream of c-myc, p53, p21WAF1/CIP1 and Bax wer e significantly highly induced, although there was no induction of Bcl-2, w hich prevents apoptosis in core-expressing cells. Thus, the HCV core protei n induced apoptosis and impaired the regulation of the cell cycle by activa ting c-myc expression, whereas the p53 and Bax pathways play a role in the induction of apoptosis.