title: Partial Hepatectomy in Acetylation-Deficient BubR1 Mice Corroborates that Chromosome Missegregation Initiates Tumorigenesis.
abstract: BACKGROUND
  Aneuploidy has been suggested as one of the major causes of cancer from the time of Boveri. In support of this notion, many studies have shown that cancer cells exhibit aneuploidy. However, there are evidences that do not support the aneuploidy hypothesis. We have previously reported that the spindle assembly checkpoint protein BubR1 is acetylated in mitosis and that the acetylation of BubR1 is crucial for checkpoint maintenance and chromosome-spindle attachment. Mice heterozygous for acetylation-deficient BubR1 (K243R/+) spontaneously develop cancer with chromosome instability. As K243R/+ mice develop hepatocellular carcinoma, we set out to test if chromosome mis-segregation was the cause of their liver cancer.
  
  
  METHODS
  Primary hepatocytes in the regenerating liver after partial hepatectomy (PH) were analyzed and compared for various mitotic parameters.
  
  
  RESULTS
  Primary hepatocytes isolated from K243R/+ mice after PH displayed a marked increase of chromosome misalignment, accompanied by an increase of micronuclei. In comparison, the number of nuclei per cell and the centrosome numbers were not different between wild-type and K243R/+ mice. Taken together, chromosome mis-segregation provokes tumorigenesis in mouse liver.
  
  
  CONCLUSIONS
  Our results corroborate that PH provides a reliable tool for assessing mitotic infidelity and cancer in mice.
authors.affiliation: Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.; Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yoo Kyung
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
authors.forename: Inai
authors.initials: I
authors.lastname: Park
authors.affiliation: Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea. HL212@snu.ac.kr.
authors.forename: Hyunsook
authors.initials: H
authors.lastname: Lee
keywords: Aneuploidy; Hepatocytes; Liver neoplasms; Mitosis; Neoplasms; Partial hepatectomy