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Series GSE20945 Query DataSets for GSE20945
Status Public on Mar 21, 2012
Title Effects of DAC treatment
Organism Homo sapiens
Experiment type Expression profiling by array
Methylation profiling by array
Summary Reversal of gene promoter DNA hypermethylation and associated abnormal gene silencing is an attractive approach to cancer therapy. The DNA methylation inhibitor, decitabine (5-aza-2'-deoxycitidine), is proving efficacious for hematological neoplasms especially at lower, less toxic, doses. Experimentally, high doses induce rapid DNA damage and cytotoxicity, but these may not explain the prolonged time to response seen in patients. Transient exposure of leukemic and solid tumor cells to clinically-relevant nanomolar doses, without causing immediate cytotoxicity or apoptosis, produces sustained reduced tumorigenicity, and for leukemia cells, diminished long-term self-renewal. These effects appear triggered by cellular reprogramming and include sustained decreases in promoter DNA methylation with associated gene re-expression, and anti-tumor changes in multiple key cellular regulatory pathways, most of which are high priority targets for pharmacologic anti-cancer strategies. Thus, low dose decitabine regimens appear to have broad applicability for cancer management.
 
Overall design [Gene expression profiling] Leukemia cell lines Kasumi-1 and KG1A are treated with 10nM DAC during 72 hours and gene expression was assayed at day 3, 7 and 14 after the start of the treatment. Appropriate mock treated samples were used as control in each case. In addition, Kasumi-1 cells were also treated with a higher dose of DAC (500nM), 100nM ARA-C and 300 nM TSA, again controlled against mock treated Kasumi-1 cells, to separate dose and agent dependent effects.
MCF7 was studied as an example of a solid tumor cell line. Therefore MCF7 cells were treated with 100nM DAC and results were assayed at day 1, day 3 and day 10.

[Methylation profiling] The effects of the demethylating agent DAC were studied in the leukemia cell line Kasumi-1 over a 28 day time course. Intermediate time points were studied at days 3, 7, 14 and 21. These results were verfied in KG1A and KG1 leukemia cell lines, at one selected time point. The effects on one primary sample were also studied. Four normal leukemia samples (PL1, 2, 4 and 5) were used as general controls. The effect of DAC was compared to ARA-C, TSA. Both mock treated and day 3 DAC treated Kasumi-1 cells were repeated. These results were verified at one selected time point for the DAC treated MCF7 breast cancer cell line.
 
Contributor(s) Van Neste L, Tsai H, Li H, Chiu Yen R, Zahnow CA, Baylin SB
Citation(s) 22439938
Submission date Mar 18, 2010
Last update date Mar 22, 2019
Contact name Leander Van Neste
Organization name Ghent University
Department Molecular Biotechnology
Lab Bioinformatics and Computational Genomics
Street address Coupure Links 653
City Ghent
ZIP/Postal code 9000
Country Belgium
 
Platforms (4)
GPL4133 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
GPL6480 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version)
GPL8490 Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2)
Samples (55)
GSM523700 Kasumi-1 10nM DAC day3 [mRNA profiling]
GSM523701 Kasumi-1 10nM DAC day7 [mRNA profiling]
GSM523720 Kasumi-1 10nM DAC day14 [mRNA profiling]
Relations
BioProject PRJNA124427

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
GSE20945_GSM843835_GSM843843_signals.txt.gz 23.2 Mb (ftp)(http) TXT
GSE20945_RAW.tar 547.1 Mb (http)(custom) TAR (of TXT)
GSE20945_signals.txt.gz 3.4 Mb (ftp)(http) TXT
Processed data included within Sample table
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