[Reversed effect of valproic acid on transcription inhibition of AML1-ETO fusion protein of kasumi-1 leukemic cell line]

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Apr;17(2):363-7.
[Article in Chinese]

Abstract

This study was aimed to investigate the mechanism of histone deacetylase (HDAC) inhibitor, valproic acid (VPA), reversing transcription inhibition of AML1-ETO fusion protein in Kasumi-1 cell line. The mRNA expressions of AML1-ETO, AML1 and cyclin D2 were detected by semi-quantitation RT-PCR after treating kasumi-1 cells with VPA at different doses/and different time points. The results indicated that the mRNA expression of AML1-ETO showed no obvious change, when kasumi-1 cells were treated with VPA. Compared with control group, the expression level of AML1 mRNA significantly increased in a dose-dependent manner. Compared with control group, the expression level of cyclin D2 mRNA significantly decreased when kasumi-1 cells had been treated with 3 mmol/L VPA as well as kasumi-1 cells were treated with different concentrations of VPA for 3 days. In conclusion, VPA could remove transcription inhibition of AML1-ETO fusion protein, increase transcription of AML1 and down-regulate mRNA expression of AML1 target gene cyclin D2 through HDAC inhibiting activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Cell Line, Tumor
  • Core Binding Factor Alpha 2 Subunit / drug effects*
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Cyclin D2 / genetics
  • Gene Expression Regulation, Leukemic
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histones / drug effects
  • Humans
  • Oncogene Proteins, Fusion / drug effects*
  • Oncogene Proteins, Fusion / genetics*
  • RUNX1 Translocation Partner 1 Protein
  • Valproic Acid / pharmacology*

Substances

  • AML1-ETO fusion protein, human
  • CCND2 protein, human
  • Core Binding Factor Alpha 2 Subunit
  • Cyclin D2
  • Histone Deacetylase Inhibitors
  • Histones
  • Oncogene Proteins, Fusion
  • RUNX1 Translocation Partner 1 Protein
  • Valproic Acid