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Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells

BACKGROUND: ID proteins are dominant negative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. Ectopic (over-)expression of ID1 extends the lifespan of primary human epithelial cells. High expression levels of ID...

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Autores principales: Manthey, Carolin, Mern, Demissew S, Gutmann, Anja, Zielinski, Anne J, Herz, Corinna, Lassmann, Silke, Hasskarl, Jens
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818612/
https://www.ncbi.nlm.nih.gov/pubmed/20070914
http://dx.doi.org/10.1186/1471-2121-11-2
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author Manthey, Carolin
Mern, Demissew S
Gutmann, Anja
Zielinski, Anne J
Herz, Corinna
Lassmann, Silke
Hasskarl, Jens
author_facet Manthey, Carolin
Mern, Demissew S
Gutmann, Anja
Zielinski, Anne J
Herz, Corinna
Lassmann, Silke
Hasskarl, Jens
author_sort Manthey, Carolin
collection PubMed
description BACKGROUND: ID proteins are dominant negative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. Ectopic (over-)expression of ID1 extends the lifespan of primary human epithelial cells. High expression levels of ID1 have been detected in multiple human malignancies, and in some have been correlated with unfavorable clinical prognosis. ID1 protein is localized at the centrosomes and forced (over-)expression of ID1 results in errors during centrosome duplication. RESULTS: Here we analyzed the steady state expression levels of the four ID-proteins in 18 tumor cell lines and assessed the number of centrosome abnormalities. While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4. Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed. CONCLUSIONS: This is the first report that shows that not only ectopic expression in tissue culture but endogenous levels of ID1 modulate centrosome numbers. Thus, our findings support the hypothesis that ID1 interferes with centrosome homeostasis, most likely contributing to genomic instability and associated tumor aggressiveness.
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spelling pubmed-28186122010-02-10 Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells Manthey, Carolin Mern, Demissew S Gutmann, Anja Zielinski, Anne J Herz, Corinna Lassmann, Silke Hasskarl, Jens BMC Cell Biol Research article BACKGROUND: ID proteins are dominant negative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. Ectopic (over-)expression of ID1 extends the lifespan of primary human epithelial cells. High expression levels of ID1 have been detected in multiple human malignancies, and in some have been correlated with unfavorable clinical prognosis. ID1 protein is localized at the centrosomes and forced (over-)expression of ID1 results in errors during centrosome duplication. RESULTS: Here we analyzed the steady state expression levels of the four ID-proteins in 18 tumor cell lines and assessed the number of centrosome abnormalities. While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4. Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed. CONCLUSIONS: This is the first report that shows that not only ectopic expression in tissue culture but endogenous levels of ID1 modulate centrosome numbers. Thus, our findings support the hypothesis that ID1 interferes with centrosome homeostasis, most likely contributing to genomic instability and associated tumor aggressiveness. BioMed Central 2010-01-14 /pmc/articles/PMC2818612/ /pubmed/20070914 http://dx.doi.org/10.1186/1471-2121-11-2 Text en Copyright ©2010 Manthey 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
Manthey, Carolin
Mern, Demissew S
Gutmann, Anja
Zielinski, Anne J
Herz, Corinna
Lassmann, Silke
Hasskarl, Jens
Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells
title Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells
title_full Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells
title_fullStr Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells
title_full_unstemmed Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells
title_short Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells
title_sort elevated endogenous expression of the dominant negative basic helix-loop-helix protein id1 correlates with significant centrosome abnormalities in human tumor cells
topic Research article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818612/
https://www.ncbi.nlm.nih.gov/pubmed/20070914
http://dx.doi.org/10.1186/1471-2121-11-2
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