Histone deacetylase inhibitors, valproic acid and trichostatin-A induce apoptosis and affect acetylation status of p53 in ERG-positive prostate cancer cells

  • Authors:
    • Wendell S. Fortson
    • Shubhalaxmi Kayarthodi
    • Yasuo  Fujimura
    • Huali Xu
    • Roland  Matthews
    • William E. Grizzle
    • Veena   N. Rao
    • Ganapathy K. Bhat
    • E. Shyam P. Reddy
  • View Affiliations

  • Published online on: April 21, 2011     https://doi.org/10.3892/ijo.2011.1014
  • Pages:111-119
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Abstract

An ETS family member, ETS Related Gene (ERG) is involved in the Ewing family of tumors as well as leukemias. Rearrangement of the ERG gene with the TMPRSS2 gene has been identified in the majority of prostate cancer patients. Additionally, overexpression of ERG is associated with unfavorable prognosis in prostate cancer patients similar to leukemia patients. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate transcription as well as epigenetic status of genes through acetylation of both histones and transcription factors. Deregulation of HATs and HDACs is frequently seen in various cancers, including prostate cancer. Many cellular oncogenes as well as tumor viral proteins are known to target either or both HATs and HDACs. Several studies have demonstrated that there are alterations of HDAC activity in prostate cancer cells. Recently, we found that ERG binds and inhibits HATs, which suggests that ERG is involved in deregulation of protein acetylation. Additionally, it has been shown that ERG is associated with a higher expression of HDACs. In this study, we tested the effect of the HDAC inhibitors valproic acid (VPA) and trichostatin-A (TSA) on ERG-positive prostate cancer cells (VCaP). We found that VPA and TSA induce apoptosis, upregulate p21/Waf1/CIP1, repress TMPRSS2-ERG expression and affect acetylation status of p53 in VCaP cells. These results suggest that HDAC inhibitors might restore HAT activity through two different ways: by inhibiting HDAC activity and by repressing HAT targeting oncoproteins such as ERG.

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July 2011
Volume 39 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Fortson, W.S., Kayarthodi, S., Fujimura, Y., Xu, H., Matthews, R., Grizzle, W.E. ... Reddy, E.S. (2011). Histone deacetylase inhibitors, valproic acid and trichostatin-A induce apoptosis and affect acetylation status of p53 in ERG-positive prostate cancer cells. International Journal of Oncology, 39, 111-119. https://doi.org/10.3892/ijo.2011.1014
MLA
Fortson, W. S., Kayarthodi, S., Fujimura, Y., Xu, H., Matthews, R., Grizzle, W. E., Rao, V. N., Bhat, G. K., Reddy, E. S."Histone deacetylase inhibitors, valproic acid and trichostatin-A induce apoptosis and affect acetylation status of p53 in ERG-positive prostate cancer cells". International Journal of Oncology 39.1 (2011): 111-119.
Chicago
Fortson, W. S., Kayarthodi, S., Fujimura, Y., Xu, H., Matthews, R., Grizzle, W. E., Rao, V. N., Bhat, G. K., Reddy, E. S."Histone deacetylase inhibitors, valproic acid and trichostatin-A induce apoptosis and affect acetylation status of p53 in ERG-positive prostate cancer cells". International Journal of Oncology 39, no. 1 (2011): 111-119. https://doi.org/10.3892/ijo.2011.1014