Analysis of the genomic response of human prostate cancer cells to histone deacetylase inhibitors

Madeleine S.Q. Kortenhorst, Michel D. Wissing, Ronald Rodriguez, Sushant K. Kachhap, Judith J.M. Jans, Petra van der Groep, Henk M.W. Verheul, Anuj Gupta, Paul O. Aiyetan, Elsken van der Wall, Michael A. Carducci, Paul J. Van Diest, Luigi Marchionni

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Histone deacetylases (HDACs) have emerged as important targets for cancer treatment. HDAC-inhibitors (HDACis) are well tolerated in patients and have been approved for the treatment of patients with cutaneous T-cell lymphoma (CTCL). To improve the clinical benefit of HDAC is in solid tumors, combination strategies with HDACis could be employed. In this study, we applied Analysis of Functional Annotation (AFA) to provide a comprehensive list of genes and pathways affected upon HDACi-treatment in prostate cancer cells. This approach provides an unbiased and objective approach to high throughput data mining. By performing AFA on gene expression data from prostate cancer cell lines DU-145 (an HDACi-sensitive cell line) and PC 3 (a relatively HDACi-resistant cell line) treated with HDACis valproic acid or vorinostat, we identified biological processes that are affected by HDACis and are therefore potential treatment targets for combination therapy. Our analysis revealed that HDAC-inhibition resulted among others in upregulation of major histocompatibility complex (MHC) genes and deregulation of the mitotic spindle checkpoint by downregulation of genes involved in mitosis. These findings were confirmed by AFA on publicly available data sets from HDACi-treated prostate cancer cells. In total, we analyzed 375 microarrays with HDACi treated and non-treated (control) prostate cancer cells. All results from this extensive analysis are provided as an online research source (available at the journal's website and at http://luigimarchionni.org/HDACIs.html). By publishing this data, we aim to enhance our understanding of the cellular changes after HDAC-inhibition, and to identify novel potential combination strategies with HDACis for the treatment of prostate cancer patients.

Original languageEnglish (US)
Pages (from-to)907-920
Number of pages14
JournalEpigenetics
Volume8
Issue number9
DOIs
StatePublished - Sep 2013
Externally publishedYes

Keywords

  • Analysis of functional annotation
  • Gene expression analysis
  • HDACis
  • Major histocompatibility complex
  • Mitotic spindle checkpoint
  • Prostate cancer
  • Valproic acid
  • Vorinostat

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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    Kortenhorst, M. S. Q., Wissing, M. D., Rodriguez, R., Kachhap, S. K., Jans, J. J. M., van der Groep, P., Verheul, H. M. W., Gupta, A., Aiyetan, P. O., van der Wall, E., Carducci, M. A., Van Diest, P. J., & Marchionni, L. (2013). Analysis of the genomic response of human prostate cancer cells to histone deacetylase inhibitors. Epigenetics, 8(9), 907-920. https://doi.org/10.4161/epi.25574