[Reversed effect of valproic acid on transcription inhibition of AML1-ETO fusion protein of kasumi-1 leukemic cell line].
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.
Zhao
Lei
L
Department of Hematology, Affiliated Hospital of Chengde Medical Collge, Chengde 067000, Hebei Province, China.
Zhu
Cui-Min
CM
Zhang
Zhi-Hua
ZH
Tian
Wen-Liang
WL
Hao
Chang-Lai
CL
D000107:Acetylation / Q000187:drug effects; D045744:Cell Line, Tumor; D050676:Core Binding Factor Alpha 2 Subunit / Q000187:drug effects* / Q000235:genetics*; D056742:Cyclin D2 / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000187:drug effects; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000187:drug effects* / Q000235:genetics*; D000075142:RUNX1 Translocation Partner 1 Protein; D014635:Valproic Acid / Q000494:pharmacology*
C107844:AML1-ETO fusion protein, human; C080336:CCND2 protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D056742:Cyclin D2; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D014635:Valproic Acid