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Trichostatin A preferentially reverses the upregulation of gene-expression levels induced by gain of chromosome 7 in colorectal cancer cell lines

Authors :
Buishand, Floryne O
Cardin, Eric
Hu, Yue
Ried, Thomas
dCSCA RMSC-2
Opleiding chirurgie
Source :
Genes Chromosomes Cancer, Buishand, F O, Cardin, E, Hu, Y & Ried, T 2017, ' Trichostatin A preferentially reverses the upregulation of gene-expression levels induced by gain of chromosome 7 in colorectal cancer cell lines ', Genes, Chromosomes and Cancer, vol. 57, no. 1, pp. 35-41 . https://doi.org/10.1002/gcc.22505, Genes Chromosomes and Cancer, 57(1), 35. Wiley-Liss Inc.
Publication Year :
2017
Publisher :
Wiley, 2017.

Abstract

Epithelial cancers are defined by a tumor-specific distribution of chromosomal aneuploidies that are maintained when cells metastasize and are conserved in cell lines derived from primary tumors. Correlations between genomic copy number and gene expression have been observed for different tumors including, colorectal (CRC), breast and pancreatic cancer. These ploidy-driven transcriptional deregulations are characterized by low-level expression changes of most genes on the affected chromosomes. The emergence of these aberrations at an early stage of tumorigenesis and the strong selection for the maintenance of these aneuploidies suggests that aneuploidy-dependent transcriptional deregulations might contribute to cellular transformation and maintenance of the malignant phenotype. The histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) has anticancer effects and is well known to lead to large scale gene expression changes. Here we assessed if TSA could disrupt the aneuploidy-driven gene expression in the aneuploid colon cancer cell line SW480 and the artificially generated aneuploid cell line DLD-1 + 7. We found that TSA increases transcriptional activity throughout the genome, yet inhibits aneuploidy-induced gene expression changes on chromosome 7. Among the TSA affected genes on chromosome 7 we identified potential CRC oncogenes. These experiments represent the first attempt to explain how histone acetylation affects aneuploidy-driven gene expression changes. This article is protected by copyright. All rights reserved.

Details

ISSN :
10452257
Volume :
57
Database :
OpenAIRE
Journal :
Genes, Chromosomes and Cancer
Accession number :
edsair.doi.dedup.....31f9cdeb7dfc6c4589b59d5b9e0b314e
Full Text :
https://doi.org/10.1002/gcc.22505