Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1/WAF1 expression, independent of histone deacetylase 1
- 21 January 2005
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Differentiation
- Vol. 12 (4), 395-404
- https://doi.org/10.1038/sj.cdd.4401567
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 p21Cip1/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.Keywords
This publication has 55 references indexed in Scilit:
- P21WAF1/CIP1 is dispensable for G1 arrest, but indispensable for apoptosis induced by sodium butyrate in MCF-7 breast cancer cellsOncogene, 2004
- Paclitaxel increases p21 synthesis and accumulation of its AKT-phosphorylated form in the cytoplasm of cancer cellsOncogene, 2003
- Downregulation of p21waf/cip-1 mediates apoptosis of human hepatocellular carcinoma cells in response to interferon-γExperimental Cell Research, 2003
- Histone-deacetylase inhibitors: novel drugs for the treatment of cancerNature Reviews Drug Discovery, 2002
- Apicidin, a Histone Deacetylase Inhibitor, Induces Apoptosis and Fas/Fas Ligand Expression in Human Acute Promyelocytic Leukemia CellsJournal of Biological Chemistry, 2002
- Histone deacetylases and cancer: causes and therapiesNature Reviews Cancer, 2001
- Inhibitors of histone deacetylase arrest cell cycle and induce apoptosis in cervical carcinoma cells circumventing human papillomavirus oncogene expressionOncogene, 2001
- Suppression of mammary carcinoma growth in vitro and in vivo by inducible expression of the Cdk inhibitor p21Cancer Gene Therapy, 2001
- Procaspase 3/p21 complex formation to resist Fas-mediated cell death is initiated as a result of the phosphorylation of p21 by protein kinase ACell Death & Differentiation, 2000
- The language of covalent histone modificationsNature, 2000