Inhibition of histone deacetylase 2 increases apoptosis and p21(Cip1/WAF1) expression, independent of histone deacetylase 1

B.H. Huang, M. Laban, C.H.W. Leung, L. Lee, C.K. Lee, Manuel Salto-Tellez, G.C. Raju, S.C. Hooi

Research output: Contribution to journalArticle

239 Citations (Scopus)

Abstract

Histone deacetylases ( HDACs) 1 and 2 share a high degree of homology and coexist within the same protein complexes. Despite their close association, each possesses unique functions. We show that the upregulation of HDAC2 in colorectal cancer occurred early at the polyp stage, was more robust and occurred more frequently than HDAC1. Similarly, while the expression of HDACs1 and 2 were increased in cervical dysplasia and invasive carcinoma, HDAC2 expression showed a clear demarcation of high-intensity staining at the transition region of dysplasia compared to HDAC1. Upon HDAC2 knockdown, cells displayed an increased number of cellular extensions reminiscent of cell differentiation. There was also an increase in apoptosis, associated with increased p21(Cip1/WAF1) expression that was independent of p53. These results suggest that HDACs, especially HDAC2, are important enzymes involved in the early events of carcinogenesis, making them candidate markers for tumor progression and targets for cancer therapy.
Original languageEnglish
Pages (from-to)395-404
Number of pages10
JournalCell Death and Differentiation
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 2005

ASJC Scopus subject areas

  • Cell Biology

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