RTC gene deletion leads to increased susceptibility to hepatocellular carcinogenesis

Objective: to study the relationship between retuculon C (RTC) gene deletion and susceptibility to hepatocellular carcinoma (HCC) in vivo. Methods and Results: Western blot analysis for cell cycle-associated proteins showed that the levels of expression of cyclin D, Cdk 2 and 4, and cdcA were not altered in the hepatocytes of RTC heterozygous (HG) mice when compared with those of mild-genotype (WG) littermates. On the other hand, p27 and c-myc expression levels were significantly decreased in liver tissue of 20 days-old HG mice and unaffected - in 10 months-old animals; cyclin A expression was unaffected in liver tissue of 20 days-old HG mice but increased - in 10 months-old ones. The level of RTC protein expression was significantly lower in HG tumors in comparison with surrounding normal hepatocytes. HG mice had significantly increased incidence of spontaneous and chemically induced HCC compared to WG littermates. Conclusions: our data suggest that the decreased level of RTC expression results in higher susceptibility to hepatocellular carcinoma.