Cargando…

Partial Hepatectomy in Acetylation-Deficient BubR1 Mice Corroborates that Chromosome Missegregation Initiates Tumorigenesis

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 tha...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Yoo-Kyung, Park, Inai, Lee, Hyunsook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Endocrine Society 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4285024/
https://www.ncbi.nlm.nih.gov/pubmed/25559578
http://dx.doi.org/10.3803/EnM.2014.29.4.561
_version_ 1782351512109842432
author Lee, Yoo-Kyung
Park, Inai
Lee, Hyunsook
author_facet Lee, Yoo-Kyung
Park, Inai
Lee, Hyunsook
author_sort Lee, Yoo-Kyung
collection PubMed
description 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. CONCLUSION: Our results corroborate that PH provides a reliable tool for assessing mitotic infidelity and cancer in mice.
format Online
Article
Text
id pubmed-4285024
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Korean Endocrine Society
record_format MEDLINE/PubMed
spelling pubmed-42850242015-01-06 Partial Hepatectomy in Acetylation-Deficient BubR1 Mice Corroborates that Chromosome Missegregation Initiates Tumorigenesis Lee, Yoo-Kyung Park, Inai Lee, Hyunsook Endocrinol Metab (Seoul) Original Article 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. CONCLUSION: Our results corroborate that PH provides a reliable tool for assessing mitotic infidelity and cancer in mice. Korean Endocrine Society 2014-12 2014-12-29 /pmc/articles/PMC4285024/ /pubmed/25559578 http://dx.doi.org/10.3803/EnM.2014.29.4.561 Text en Copyright © 2014 Korean Endocrine Society http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Lee, Yoo-Kyung
Park, Inai
Lee, Hyunsook
Partial Hepatectomy in Acetylation-Deficient BubR1 Mice Corroborates that Chromosome Missegregation Initiates Tumorigenesis
title Partial Hepatectomy in Acetylation-Deficient BubR1 Mice Corroborates that Chromosome Missegregation Initiates Tumorigenesis
title_full Partial Hepatectomy in Acetylation-Deficient BubR1 Mice Corroborates that Chromosome Missegregation Initiates Tumorigenesis
title_fullStr Partial Hepatectomy in Acetylation-Deficient BubR1 Mice Corroborates that Chromosome Missegregation Initiates Tumorigenesis
title_full_unstemmed Partial Hepatectomy in Acetylation-Deficient BubR1 Mice Corroborates that Chromosome Missegregation Initiates Tumorigenesis
title_short Partial Hepatectomy in Acetylation-Deficient BubR1 Mice Corroborates that Chromosome Missegregation Initiates Tumorigenesis
title_sort partial hepatectomy in acetylation-deficient bubr1 mice corroborates that chromosome missegregation initiates tumorigenesis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4285024/
https://www.ncbi.nlm.nih.gov/pubmed/25559578
http://dx.doi.org/10.3803/EnM.2014.29.4.561
work_keys_str_mv AT leeyookyung partialhepatectomyinacetylationdeficientbubr1micecorroboratesthatchromosomemissegregationinitiatestumorigenesis
AT parkinai partialhepatectomyinacetylationdeficientbubr1micecorroboratesthatchromosomemissegregationinitiatestumorigenesis
AT leehyunsook partialhepatectomyinacetylationdeficientbubr1micecorroboratesthatchromosomemissegregationinitiatestumorigenesis