Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-09

AUTHORS

Elza C. de Bruin, Simone van de Pas, Cornelis J. H. van de Velde, J. Han J. M. van Krieken, Lucy T. C. Peltenburg, Corrie A. M. Marijnen, Jan Paul Medema

ABSTRACT

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. More... »

PAGES

1671-1680

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10495-007-0088-2

DOI

http://dx.doi.org/10.1007/s10495-007-0088-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000755626

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17610066


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