Histone acetyltransferase PCAF up-regulated cell apoptosis in hepatocellular carcinoma via acetylating histone H4 and inactivating AKT signaling

Mol Cancer. 2013 Aug 27;12(1):96. doi: 10.1186/1476-4598-12-96.

Abstract

Background: PCAF is an important intrinsic histone acetyltransferases. This study tried to establish the effect of PCAF on HCC cell apoptosis.

Method: Both in vitro and in vivo experiments including IHC, DAPI staining, caspase 3/7 activity assay, BrdU assay, MTT assay, western immunoblotting and co-immunoprecipitation were used here.

Results: PCAF was found to be expressed at the low level in most of HCC cell lines. PCAF overexpression induced cell apoptosis and growth arrest with increased Histone H4 acetylation and inactivation of AKT signaling in Huh7 and HepG2 cells. The opposite results were obtained by silencing PCAF in Hep3B cells. The co-immunoprecipitation assay confirmed that PCAF protein was bound with histone H4 protein in the nucleus of Hep3B cells. Finally, the in vivo experiment confirmed the findings mentioned-above.

Conclusion: These data identified PCAF promotes cell apoptosis and functions as a HCC repressor through acetylating histone H4 and inactivating AKT signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Apoptosis*
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / pathology
  • Cell Proliferation
  • Gene Knockdown Techniques
  • Hep G2 Cells
  • Histones / metabolism*
  • Humans
  • Liver Neoplasms, Experimental / metabolism*
  • Liver Neoplasms, Experimental / pathology
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • Tumor Burden
  • Up-Regulation
  • p300-CBP Transcription Factors / physiology*

Substances

  • Histones
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Proto-Oncogene Proteins c-akt