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| Status |
Public on Jan 01, 2014 |
| Title |
Time-course gene expression profiles of gefitinib-sensitive or -resistant lung adenocarcinoma cells stimulated with EGF, in the presence or absence of gefitinib, EGF receptor tyrosine kinase-specific inhibitor |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), induces substantial clinical responses for non-small cell lung cancer (NSCLC) cells harboring EGFR activating mutations, but most of them invariably develop resistance. By generating a gefitinib resistance (PC9GR) from a human NSCLC-derived drug sensitive cell line (PC9), we studied differences of transcription dynamics between them by the aid of a computational decoupling of hidden regulatory signals from time course gene expression profiles. Given a collection of transcription factors (TFs) and their regulatory targets, the method captured temporally-synchronized shifts in evolving expression of target genes sharing each TF regulatory unit, and drew underlying regulatory signals. The analysis identified sterol regulatory element binding protein 1 (SREBP-1) as a key regulatory agent that facilitates the maintenance of drug tolerance, involving transcription controls of a G1-specific cyclin dependent kinase inhibitor whose expression was specifically elevated in PC9, but in turn, reduced in PC9GR
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| Overall design |
Gefitinib-resistance cell line (PC9GR) was established derived from lung adenocarcinoma cell line PC9. PC9 cells and PC9GR cells were treated with the four different conditions, control (No treatment), EGF-treatment, gefitinib-treatment, and both gefitinib and EGF-treatment. In each condition, the gene expression was measured at 26 time points during 24 hrs.
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| Contributor(s) |
Gotoh N |
| Citation(s) |
26268703 |
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| Submission date |
Dec 07, 2011 |
| Last update date |
Jun 01, 2018 |
| Contact name |
Noriko Gotoh |
| E-mail(s) |
[email protected]
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| Organization name |
The University of Tokyo
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| Department |
Institute of Medical Science
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| Lab |
Division of Systems Biomedical Technology
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| Street address |
4-6-1,Shirokanedai
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| City |
Minato-ku |
| State/province |
Tokyo |
| ZIP/Postal code |
108-8639 |
| Country |
Japan |
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| Platforms (1) |
| GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
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| Samples (208)
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| Relations |
| BioProject |
PRJNA149785 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE34228_RAW.tar |
459.8 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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