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Sister chromatid cohesion defects are associated with chromosome instability in Hodgkin lymphoma cells
BACKGROUND: Chromosome instability manifests as an abnormal chromosome complement and is a pathogenic event in cancer. Although a correlation between abnormal chromosome numbers and cancer exist, the underlying mechanisms that cause chromosome instability are poorly understood. Recent data suggests...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751861/ https://www.ncbi.nlm.nih.gov/pubmed/23962039 http://dx.doi.org/10.1186/1471-2407-13-391 |
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author | Sajesh, Babu V Lichtensztejn, Zelda McManus, Kirk J |
author_facet | Sajesh, Babu V Lichtensztejn, Zelda McManus, Kirk J |
author_sort | Sajesh, Babu V |
collection | PubMed |
description | BACKGROUND: Chromosome instability manifests as an abnormal chromosome complement and is a pathogenic event in cancer. Although a correlation between abnormal chromosome numbers and cancer exist, the underlying mechanisms that cause chromosome instability are poorly understood. Recent data suggests that aberrant sister chromatid cohesion causes chromosome instability and thus contributes to the development of cancer. Cohesion normally functions by tethering nascently synthesized chromatids together to prevent premature segregation and thus chromosome instability. Although the prevalence of aberrant cohesion has been reported for some solid tumors, its prevalence within liquid tumors is unknown. Consequently, the current study was undertaken to evaluate aberrant cohesion within Hodgkin lymphoma, a lymphoid malignancy that frequently exhibits chromosome instability. METHODS: Using established cytogenetic techniques, the prevalence of chromosome instability and aberrant cohesion was examined within mitotic spreads generated from five commonly employed Hodgkin lymphoma cell lines (L-1236, KM-H2, L-428, L-540 and HDLM-2) and a lymphocyte control. Indirect immunofluorescence and Western blot analyses were performed to evaluate the localization and expression of six critical proteins involved in the regulation of sister chromatid cohesion. RESULTS: We first confirmed that all five Hodgkin lymphoma cell lines exhibited chromosome instability relative to the lymphocyte control. We then determined that each Hodgkin lymphoma cell line exhibited cohesion defects that were subsequently classified into mild, moderate or severe categories. Surprisingly, ~50% of the mitotic spreads generated from L-540 and HDLM-2 harbored cohesion defects. To gain mechanistic insight into the underlying cause of the aberrant cohesion we examined the localization and expression of six critical proteins involved in cohesion. Although all proteins produced the expected nuclear localization pattern, striking differences in RAD21 expression was observed: RAD21 expression was lowest in L-540 and highest within HDLM-2. CONCLUSION: We conclude that aberrant cohesion is a common feature of all five Hodgkin lymphoma cell lines evaluated. We further conclude that aberrant RAD21 expression is a strong candidate to underlie aberrant cohesion, chromosome instability and contribute to the development of the disease. Our findings support a growing body of evidence suggesting that cohesion defects and aberrant RAD21 expression are pathogenic events that contribute to tumor development. |
format | Online Article Text |
id | pubmed-3751861 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-37518612013-08-24 Sister chromatid cohesion defects are associated with chromosome instability in Hodgkin lymphoma cells Sajesh, Babu V Lichtensztejn, Zelda McManus, Kirk J BMC Cancer Research Article BACKGROUND: Chromosome instability manifests as an abnormal chromosome complement and is a pathogenic event in cancer. Although a correlation between abnormal chromosome numbers and cancer exist, the underlying mechanisms that cause chromosome instability are poorly understood. Recent data suggests that aberrant sister chromatid cohesion causes chromosome instability and thus contributes to the development of cancer. Cohesion normally functions by tethering nascently synthesized chromatids together to prevent premature segregation and thus chromosome instability. Although the prevalence of aberrant cohesion has been reported for some solid tumors, its prevalence within liquid tumors is unknown. Consequently, the current study was undertaken to evaluate aberrant cohesion within Hodgkin lymphoma, a lymphoid malignancy that frequently exhibits chromosome instability. METHODS: Using established cytogenetic techniques, the prevalence of chromosome instability and aberrant cohesion was examined within mitotic spreads generated from five commonly employed Hodgkin lymphoma cell lines (L-1236, KM-H2, L-428, L-540 and HDLM-2) and a lymphocyte control. Indirect immunofluorescence and Western blot analyses were performed to evaluate the localization and expression of six critical proteins involved in the regulation of sister chromatid cohesion. RESULTS: We first confirmed that all five Hodgkin lymphoma cell lines exhibited chromosome instability relative to the lymphocyte control. We then determined that each Hodgkin lymphoma cell line exhibited cohesion defects that were subsequently classified into mild, moderate or severe categories. Surprisingly, ~50% of the mitotic spreads generated from L-540 and HDLM-2 harbored cohesion defects. To gain mechanistic insight into the underlying cause of the aberrant cohesion we examined the localization and expression of six critical proteins involved in cohesion. Although all proteins produced the expected nuclear localization pattern, striking differences in RAD21 expression was observed: RAD21 expression was lowest in L-540 and highest within HDLM-2. CONCLUSION: We conclude that aberrant cohesion is a common feature of all five Hodgkin lymphoma cell lines evaluated. We further conclude that aberrant RAD21 expression is a strong candidate to underlie aberrant cohesion, chromosome instability and contribute to the development of the disease. Our findings support a growing body of evidence suggesting that cohesion defects and aberrant RAD21 expression are pathogenic events that contribute to tumor development. BioMed Central 2013-08-20 /pmc/articles/PMC3751861/ /pubmed/23962039 http://dx.doi.org/10.1186/1471-2407-13-391 Text en Copyright © 2013 Sajesh et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Sajesh, Babu V Lichtensztejn, Zelda McManus, Kirk J Sister chromatid cohesion defects are associated with chromosome instability in Hodgkin lymphoma cells |
title | Sister chromatid cohesion defects are associated with chromosome instability in Hodgkin lymphoma cells |
title_full | Sister chromatid cohesion defects are associated with chromosome instability in Hodgkin lymphoma cells |
title_fullStr | Sister chromatid cohesion defects are associated with chromosome instability in Hodgkin lymphoma cells |
title_full_unstemmed | Sister chromatid cohesion defects are associated with chromosome instability in Hodgkin lymphoma cells |
title_short | Sister chromatid cohesion defects are associated with chromosome instability in Hodgkin lymphoma cells |
title_sort | sister chromatid cohesion defects are associated with chromosome instability in hodgkin lymphoma cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751861/ https://www.ncbi.nlm.nih.gov/pubmed/23962039 http://dx.doi.org/10.1186/1471-2407-13-391 |
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