Role of a novel oncogenic protein, gankyrin, in hepatocyte proliferation

Background. Gankyrin is a novel oncogenic protein ubiquitously overexpressed in hepatocellular carcinoma. However, little is known about the physiological role of gankyrin in the cell-cycle progression of normal noncancerous hepatocytes at present. We investigated the possible involvement of gankyrin in hepatocyte proliferation and examined the expression of gankyrin in the liver of patients with fulminant hepatic failure (FHF). Methods. We examined the potential cell-cycle dependence of gankyrin expression in primary hepatocytes after mitogenic stimulation. Gankyrin expression level was also measured in the liver tissue of patients with FHF, as a model of active proliferation of human hepatocytes associated with liver regeneration. Results. In primary hepatocytes, gankyrin was expressed in the G1/S phase of the cell cycle at 48h after mitogenic stimulation, which coincided with the phase of cyclin D1 RNA upregulation and RB1 protein downregulation. Using a quantitative reverse transcription polymerase chain reaction assay, we showed that gankyrin mRNA in the liver tissue of patients with FHF was expressed abundantly compared with that in healthy individuals (median, 109.7 [interquartile range; IQR, 49.0-186.4] vs median, 22.4 [IQR, 1.4-77.3] copies per sample, respectively). Conclusions. The upregulation of gankyrin correlates with cell-cycle progression in normal hepatocyte proliferation. Thus, gankyrin may play a role in cell-cycle progression in normal hepatocytes. Moreover, gankyrin may have a role in the pathophysiology of FHF.