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Series GSE11766 Query DataSets for GSE11766
Status Public on Jun 13, 2008
Title Transcriptional repression of c-Myb and GATA-2 is involved in the effects of C/EBPα in p210 BCR/ABL-expressing cells
Organism Mus musculus
Experiment type Expression profiling by array
Summary Levels of C/EBPα are low in myeloid blast crisis (BC) of chronic myelogenous leukemia (CML) and its expression in p210BCR/ABL-expressing hematopoietic cells induces granulocytic differentiation, inhibits proliferation and suppresses leukemogenesis. To assess the mechanisms involved in these effects, C/EBPα targets were identified by microarray analyses. Upon C/EBPα activation, expression of c-Myb and GATA-2 was repressed in 32D-BCR/ABL, K562 and CML-BC primary cells but only c-Myb levels decreased slightly in CD34+ normal progenitors. The role of these two genes for the biological effects of C/EBPα was assessed by perturbing their expression in K562 cells. Expression of c-Myb blocked the proliferation inhibition and differentiation-inducing effects of C/EBPα while c-Myb siRNA treatment enhanced C/EBPα-mediated proliferation inhibition and induced changes in gene expression indicative of monocytic differentiation. GATA-2 expression suppressed the proliferation inhibitory effect of C/EBPα but blocked in part the effect on differentiation; GATA-2 siRNA treatment had no effects on C/EBPα induction of differentiation but inhibited proliferation of K562 cells, alone or upon C/EBPα activation. In summary, the effects of C/EBPα in p210BCR/ABL -expressing cells depend, in part, on transcriptional repression of c-Myb and GATA-2. Since perturbation of c-Myb and GATA-2 expression has non identical consequences for proliferation and differentiation of K562 cells, the effects of C/EBPα appear to involve different transcription-regulated targets.
 
Overall design 48 samples total. 4-HT-treated 32D-BCR/ABL cells transduced with the MigRI empty vector, MigRI WT C/EBPα-ER , MigRI K298E C/EBPα-ER (a DNA binding-deficient mutant) or MigRI-delta(177-191) C/EBPα-ER (a mutant deficient in CDK2/CDK4 interaction). Total RNA was extracted at 0, 6, 9 and 12h post-4-HT treatment in triplicate and hybridized onto the Affymetrix MOE430 _2 array.
 
Citation(s) 18550858
Submission date Jun 12, 2008
Last update date Feb 11, 2019
Contact name Robert Vincent Martinez
E-mail rxmartinez@wyeth.com
Phone 617-665-7008
Fax 617-665-8350
Organization name Wyeth Research
Department Biological Technologies
Street address 35 Cambridgepark Drive
City Cambridge
State/province MA
ZIP/Postal code 02140
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (48)
GSM297960 MigRI_empty_vector_0hr_1
GSM297961 MigRI_empty_vector_0hr_2
GSM297962 MigRI_empty_vector_0hr_3
Relations
BioProject PRJNA105947

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE11766_RAW.tar 280.6 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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