[Effects of AML1-ETO on transcription activity of p21WAF1/CIP1 gene promoter].
OBJECTIVE
To observe the effects of AML1-ETO fusion gene on the transcription activity of p21WAF1/CIP1 gene. And to explore the enhancement of leukemia pathogenesis of AML1-ETO.


METHODS
The luciferase reporter plasmids of p21WAF1/CIP1 gene promoter were constructed, and co-transfected into CV-1 cells with AML1-ETO, AML1b and AML1a expression plasmids. The trans-activity of p21WAF1/CIP1 gene promoter was assayed by luminometer.


RESULTS
AML1-ETO exhibited a distinct inhibition activity of p21WAF1/CIP1 gene promoter with a sequence-specificity and dosage-dependent manner. The trans-activity of p21WAF1/CIP1 gene promoter decreased to (19 +/- 4)% compared to control group, when 1000 ng pCMV5-AML1-ETO plasmid was used. AML1b and AMLla showed less inhibition activity. The trans-activity of p21WAF1/CIP1 gene promoter decreased to (61 +/- 16)% and (59 +/- 16)% compared to control group, respectively, when 1000 ng plasmid was used.


CONCLUSIONS
AML1-ETO exhibits more inhibition activity of p21WAF1/CIP1 gene promoter than AML1b and AMLla, results from recruiting transcription co-repression complex efficiently by ETO. Based on previous researches, the effects of exogenous AML1-ETO on p21WAF1/CIP1 gene promote may be dependent on the type of cell lines.
Wei
Hui
H
State Key Laboratory of Experimental Hematology, and Blood Diseases Hospital, Institute of Hematology, CAMS & PUMC, Tianjin, China.
Liu
Xiang-rong
XR
Liu
Hang
H
Rao
Qing
Q
Wang
Min
M
Wang
Jian-xiang
JX
D000818:Animals; D002460:Cell Line; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D000882:Haplorhini; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000075142:RUNX1 Translocation Partner 1 Protein; D014158:Transcription, Genetic; D014162:Transfection
C107844:AML1-ETO fusion protein, human; C493956:CDKN1A protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein