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

Floryne O Buishand, Eric Cardin, Yue Hu, Thomas Ried

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 suggest 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.

Original languageEnglish
Pages (from-to)35-41
Number of pages7
JournalGenes, Chromosomes and Cancer
Volume57
Issue number1
Early online date23 Sept 2017
DOIs
Publication statusPublished - 15 Nov 2017

Keywords / Materials (for Non-textual outputs)

  • Aneuploidy
  • Cell Line, Tumor
  • Chromosomes, Human, Pair 7
  • Colorectal Neoplasms
  • Gene Expression Regulation, Neoplastic
  • Histone Deacetylase Inhibitors
  • Humans
  • Hydroxamic Acids
  • Up-Regulation
  • Journal Article
  • Research Support, Non-U.S. Gov't

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