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CD44 Expression in Intestinal Epithelium and Colorectal Cancer Is Independent of p53 Status

CD44 marks stem cell-like cells in a number of tumour types, including colorectal cancer (CRC), while aberrant CD44 expression conveys increased tumourigenic, invasive, and metastatic potential. Previous data indicate that CD44 is a direct target of p53-mediated transcriptional repression in breast...

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Autores principales: Zeilstra, Jurrit, Joosten, Sander P. J., Vermeulen, Louis, Koster, Jan, Medema, Jan Paul, Versteeg, Rogier, Spaargaren, Marcel, Pals, Steven T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756983/
https://www.ncbi.nlm.nih.gov/pubmed/24009708
http://dx.doi.org/10.1371/journal.pone.0072849
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author Zeilstra, Jurrit
Joosten, Sander P. J.
Vermeulen, Louis
Koster, Jan
Medema, Jan Paul
Versteeg, Rogier
Spaargaren, Marcel
Pals, Steven T.
author_facet Zeilstra, Jurrit
Joosten, Sander P. J.
Vermeulen, Louis
Koster, Jan
Medema, Jan Paul
Versteeg, Rogier
Spaargaren, Marcel
Pals, Steven T.
author_sort Zeilstra, Jurrit
collection PubMed
description CD44 marks stem cell-like cells in a number of tumour types, including colorectal cancer (CRC), while aberrant CD44 expression conveys increased tumourigenic, invasive, and metastatic potential. Previous data indicate that CD44 is a direct target of p53-mediated transcriptional repression in breast cancer. Since inactivating p53 mutations are frequent genetic events in CRC these could unleash expression of CD44. In the present study, we therefore explored the relation between p53 mutational status and CD44 expression in a cohort of 90 localized primary CRCs and studied the effect of radiation-induced p53 activation on CD44 expression. Interestingly, we observed that, in contrast to breast cancer, loss of function p53 mutations were not associated with elevated CD44 expression in colon cancer. Moreover, DNA-damage induced p53 activation did not result in repression of CD44 expression, neither in colon cancer cells nor in normal intestinal epithelial cells. Our data demonstrate that CD44 expression in normal and malignant intestinal epithelial cells is not regulated by p53, implying that regulation of this potentially important therapeutic target is tissue and cancer-type specific.
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spelling pubmed-37569832013-09-05 CD44 Expression in Intestinal Epithelium and Colorectal Cancer Is Independent of p53 Status Zeilstra, Jurrit Joosten, Sander P. J. Vermeulen, Louis Koster, Jan Medema, Jan Paul Versteeg, Rogier Spaargaren, Marcel Pals, Steven T. PLoS One Research Article CD44 marks stem cell-like cells in a number of tumour types, including colorectal cancer (CRC), while aberrant CD44 expression conveys increased tumourigenic, invasive, and metastatic potential. Previous data indicate that CD44 is a direct target of p53-mediated transcriptional repression in breast cancer. Since inactivating p53 mutations are frequent genetic events in CRC these could unleash expression of CD44. In the present study, we therefore explored the relation between p53 mutational status and CD44 expression in a cohort of 90 localized primary CRCs and studied the effect of radiation-induced p53 activation on CD44 expression. Interestingly, we observed that, in contrast to breast cancer, loss of function p53 mutations were not associated with elevated CD44 expression in colon cancer. Moreover, DNA-damage induced p53 activation did not result in repression of CD44 expression, neither in colon cancer cells nor in normal intestinal epithelial cells. Our data demonstrate that CD44 expression in normal and malignant intestinal epithelial cells is not regulated by p53, implying that regulation of this potentially important therapeutic target is tissue and cancer-type specific. Public Library of Science 2013-08-29 /pmc/articles/PMC3756983/ /pubmed/24009708 http://dx.doi.org/10.1371/journal.pone.0072849 Text en © 2013 Zeilstra et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zeilstra, Jurrit
Joosten, Sander P. J.
Vermeulen, Louis
Koster, Jan
Medema, Jan Paul
Versteeg, Rogier
Spaargaren, Marcel
Pals, Steven T.
CD44 Expression in Intestinal Epithelium and Colorectal Cancer Is Independent of p53 Status
title CD44 Expression in Intestinal Epithelium and Colorectal Cancer Is Independent of p53 Status
title_full CD44 Expression in Intestinal Epithelium and Colorectal Cancer Is Independent of p53 Status
title_fullStr CD44 Expression in Intestinal Epithelium and Colorectal Cancer Is Independent of p53 Status
title_full_unstemmed CD44 Expression in Intestinal Epithelium and Colorectal Cancer Is Independent of p53 Status
title_short CD44 Expression in Intestinal Epithelium and Colorectal Cancer Is Independent of p53 Status
title_sort cd44 expression in intestinal epithelium and colorectal cancer is independent of p53 status
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756983/
https://www.ncbi.nlm.nih.gov/pubmed/24009708
http://dx.doi.org/10.1371/journal.pone.0072849
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