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Kinetochore genes are coordinately up-regulated in human tumors as part of a FoxM1-related cell division program

The key player in directing proper chromosome segregation is the macromolecular kinetochore complex, which mediates DNA–microtubule interactions. Previous studies testing individual kinetochore genes documented examples of their overexpression in tumors relative to normal tissue, leading to proposal...

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Autores principales: Thiru, Prathapan, Kern, David M., McKinley, Kara L., Monda, Julie K., Rago, Florencia, Su, Kuan-Chung, Tsinman, Tonia, Yarar, Defne, Bell, George W., Cheeseman, Iain M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072572/
https://www.ncbi.nlm.nih.gov/pubmed/24829384
http://dx.doi.org/10.1091/mbc.E14-03-0837
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author Thiru, Prathapan
Kern, David M.
McKinley, Kara L.
Monda, Julie K.
Rago, Florencia
Su, Kuan-Chung
Tsinman, Tonia
Yarar, Defne
Bell, George W.
Cheeseman, Iain M.
author_facet Thiru, Prathapan
Kern, David M.
McKinley, Kara L.
Monda, Julie K.
Rago, Florencia
Su, Kuan-Chung
Tsinman, Tonia
Yarar, Defne
Bell, George W.
Cheeseman, Iain M.
author_sort Thiru, Prathapan
collection PubMed
description The key player in directing proper chromosome segregation is the macromolecular kinetochore complex, which mediates DNA–microtubule interactions. Previous studies testing individual kinetochore genes documented examples of their overexpression in tumors relative to normal tissue, leading to proposals that up-regulation of specific kinetochore genes may promote tumor progression. However, kinetochore components do not function in isolation, and previous studies did not comprehensively compare the expression behavior of kinetochore components. Here we analyze the expression behavior of the full range of human kinetochore components in diverse published expression compendia, including normal tissues and tumor samples. Our results demonstrate that kinetochore genes are rarely overexpressed individually. Instead, we find that core kinetochore genes are coordinately regulated with other cell division genes under virtually all conditions. This expression pattern is strongly correlated with the expression of the forkhead transcription factor FoxM1, which binds to the majority of cell division promoters. These observations suggest that kinetochore gene up-regulation in cancer reflects a general activation of the cell division program and that altered expression of individual kinetochore genes is unlikely to play a causal role in tumorigenesis.
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spelling pubmed-40725722014-09-16 Kinetochore genes are coordinately up-regulated in human tumors as part of a FoxM1-related cell division program Thiru, Prathapan Kern, David M. McKinley, Kara L. Monda, Julie K. Rago, Florencia Su, Kuan-Chung Tsinman, Tonia Yarar, Defne Bell, George W. Cheeseman, Iain M. Mol Biol Cell Articles The key player in directing proper chromosome segregation is the macromolecular kinetochore complex, which mediates DNA–microtubule interactions. Previous studies testing individual kinetochore genes documented examples of their overexpression in tumors relative to normal tissue, leading to proposals that up-regulation of specific kinetochore genes may promote tumor progression. However, kinetochore components do not function in isolation, and previous studies did not comprehensively compare the expression behavior of kinetochore components. Here we analyze the expression behavior of the full range of human kinetochore components in diverse published expression compendia, including normal tissues and tumor samples. Our results demonstrate that kinetochore genes are rarely overexpressed individually. Instead, we find that core kinetochore genes are coordinately regulated with other cell division genes under virtually all conditions. This expression pattern is strongly correlated with the expression of the forkhead transcription factor FoxM1, which binds to the majority of cell division promoters. These observations suggest that kinetochore gene up-regulation in cancer reflects a general activation of the cell division program and that altered expression of individual kinetochore genes is unlikely to play a causal role in tumorigenesis. The American Society for Cell Biology 2014-07-01 /pmc/articles/PMC4072572/ /pubmed/24829384 http://dx.doi.org/10.1091/mbc.E14-03-0837 Text en © 2014 Thiru et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Thiru, Prathapan
Kern, David M.
McKinley, Kara L.
Monda, Julie K.
Rago, Florencia
Su, Kuan-Chung
Tsinman, Tonia
Yarar, Defne
Bell, George W.
Cheeseman, Iain M.
Kinetochore genes are coordinately up-regulated in human tumors as part of a FoxM1-related cell division program
title Kinetochore genes are coordinately up-regulated in human tumors as part of a FoxM1-related cell division program
title_full Kinetochore genes are coordinately up-regulated in human tumors as part of a FoxM1-related cell division program
title_fullStr Kinetochore genes are coordinately up-regulated in human tumors as part of a FoxM1-related cell division program
title_full_unstemmed Kinetochore genes are coordinately up-regulated in human tumors as part of a FoxM1-related cell division program
title_short Kinetochore genes are coordinately up-regulated in human tumors as part of a FoxM1-related cell division program
title_sort kinetochore genes are coordinately up-regulated in human tumors as part of a foxm1-related cell division program
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072572/
https://www.ncbi.nlm.nih.gov/pubmed/24829384
http://dx.doi.org/10.1091/mbc.E14-03-0837
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