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Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo
The level of apoptosis in rectal carcinomas of patients treated by surgery only predicts local failure; patients with intrinsically high-apoptotic tumors develop less local recurrences than patients with low levels of apoptosis. To identify genes involved in this intrinsic apoptotic process in vivo,...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Kluwer Academic Publishers-Plenum Publishers
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668623/ https://www.ncbi.nlm.nih.gov/pubmed/17610066 http://dx.doi.org/10.1007/s10495-007-0088-2 |
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author | de Bruin, Elza C. van de Pas, Simone van de Velde, Cornelis J. H. van Krieken, J. Han J. M. Peltenburg, Lucy T. C. Marijnen, Corrie A. M. Medema, Jan Paul |
author_facet | de Bruin, Elza C. van de Pas, Simone van de Velde, Cornelis J. H. van Krieken, J. Han J. M. Peltenburg, Lucy T. C. Marijnen, Corrie A. M. Medema, Jan Paul |
author_sort | de Bruin, Elza C. |
collection | PubMed |
description | The level of apoptosis in rectal carcinomas of patients treated by surgery only predicts local failure; patients with intrinsically high-apoptotic tumors develop less local recurrences than patients with low levels of apoptosis. To identify genes involved in this intrinsic apoptotic process in vivo, 47 rectal tumors with known apoptotic phenotype (24 low- and 23 high-apoptotic) were analyzed by oligonucleotide microarray technology. We identified several genes differentially expressed between low- and high-apoptotic tumors. Unsupervised clustering of the tumors based on expression levels of these genes separated the low-apoptotic from the high-apoptotic tumors, indicating a gene expression-dependent regulation. In addition, this clustering revealed two subgroups of high-apoptotic tumors. One high-apoptotic subgroup showed subtle differences in mRNA and protein expression of the known apoptotic regulators BAX, cIAP2 and ARC compared to the low-apoptotic tumors. The other subgroup of high-apoptotic tumors showed high expression of immune-related genes; predominantly HLA class II and chemokines, but also HLA class I and interferon-inducible genes were highly expressed. Immunohistochemistry revealed HLA-DR expression in epithelial tumor cells in 70% of these high-apoptotic tumors. The expression data suggest that high levels of apoptosis in rectal carcinoma patients can be the result of either slightly altered expression of known pro- and anti-apoptotic genes or high expression of immune-related genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi: 10.1007/s10495-007-0088-2) contains supplementary material, which is available to authorized users. |
format | Text |
id | pubmed-2668623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Kluwer Academic Publishers-Plenum Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-26686232009-04-23 Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo de Bruin, Elza C. van de Pas, Simone van de Velde, Cornelis J. H. van Krieken, J. Han J. M. Peltenburg, Lucy T. C. Marijnen, Corrie A. M. Medema, Jan Paul Apoptosis Original Paper The level of apoptosis in rectal carcinomas of patients treated by surgery only predicts local failure; patients with intrinsically high-apoptotic tumors develop less local recurrences than patients with low levels of apoptosis. To identify genes involved in this intrinsic apoptotic process in vivo, 47 rectal tumors with known apoptotic phenotype (24 low- and 23 high-apoptotic) were analyzed by oligonucleotide microarray technology. We identified several genes differentially expressed between low- and high-apoptotic tumors. Unsupervised clustering of the tumors based on expression levels of these genes separated the low-apoptotic from the high-apoptotic tumors, indicating a gene expression-dependent regulation. In addition, this clustering revealed two subgroups of high-apoptotic tumors. One high-apoptotic subgroup showed subtle differences in mRNA and protein expression of the known apoptotic regulators BAX, cIAP2 and ARC compared to the low-apoptotic tumors. The other subgroup of high-apoptotic tumors showed high expression of immune-related genes; predominantly HLA class II and chemokines, but also HLA class I and interferon-inducible genes were highly expressed. Immunohistochemistry revealed HLA-DR expression in epithelial tumor cells in 70% of these high-apoptotic tumors. The expression data suggest that high levels of apoptosis in rectal carcinoma patients can be the result of either slightly altered expression of known pro- and anti-apoptotic genes or high expression of immune-related genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi: 10.1007/s10495-007-0088-2) contains supplementary material, which is available to authorized users. Kluwer Academic Publishers-Plenum Publishers 2007-07-03 2007-09 /pmc/articles/PMC2668623/ /pubmed/17610066 http://dx.doi.org/10.1007/s10495-007-0088-2 Text en © Springer Science+Business Media, LLC 2007 |
spellingShingle | Original Paper de Bruin, Elza C. van de Pas, Simone van de Velde, Cornelis J. H. van Krieken, J. Han J. M. Peltenburg, Lucy T. C. Marijnen, Corrie A. M. Medema, Jan Paul Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo |
title | Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo |
title_full | Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo |
title_fullStr | Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo |
title_full_unstemmed | Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo |
title_short | Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo |
title_sort | gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668623/ https://www.ncbi.nlm.nih.gov/pubmed/17610066 http://dx.doi.org/10.1007/s10495-007-0088-2 |
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