Abstract
Abstract Aberrant expression of hepatoma up-regulated protein, HURP, was found in hepatocellular carcinoma (HCC). Recent studies revealed that HURP is an essential factor during mitosis. However, the function of HURP in an in vivo context has not been well studied. In this study, we have concentrated our efforts on the pathological effects of Hurp deficiency during liver regeneration. We generated Hurp knockout (KO) mice to investigate the function of Hurp involved in hepatocyte cell cycle progression; we used the in vivo model of two-third partial-hepatectomy (PH) to induce synchronous cell cycle entry in liver. Our results revealed striking phenotypes of mitotic errors and chromosome instability in the Hurp KO livers. These phenotypes include impaired cell cycle progression as revealed by delayed entry of S-phase and M-phase of hepatocytes post-PH; mitotic infidelity as revealed by lagging chromosomes, multi-polar segregation and unequal segregation; aberrant nuclei of micro-nucleus, multi-nucleus and atypical nuclear morphology were frequently observed in the Hurp KO livers. Mechanistically, these abnormalities caused by Hurp deficiency did not turn on the spindle checkpoint machinery, such as BubR1 and Mad2, but up-regulated p21 expression to delay the cell cycle progression in liver. As an evidence of chronic liver damage, we observed continuously elevated serum ALT levels in Hurp KO mice post-PH. Together, these phenotypes in liver indicated that Hurp deficiency interferes spindle checkpoint (directly or indirectly), leading to mitotic infidelities, and possibly causes DNA breakage during chromatin segregation; this DNA breakage can further induce p21 to delay cell cycle during liver regeneration which is accompanying by chronic liver damages. All of these abnormalities may further lead to enhanced carcinogenesis in liver, which is currently under investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2411. doi:10.1158/1538-7445.AM2011-2411
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call