 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Feb 09, 2009 |
| Title |
Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP-on-chip |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Genome binding/occupancy profiling by genome tiling array
|
| Summary |
Previous studies have revealed that UV-stimulation of a variety of cells leads to activation of the EGF receptor, induction of Egr1, growth inhibition and apoptosis. On the other hand both Egr1 and EGF receptor activation are implicated in promoting the progression of prostate cancer. We treated M12 tumorigenic prostate epithelial cells which express little Egr1 with UV irradiation which rapidly activated the EGF receptor and elevated Egr1. Treatment with specific EGFR and ERKI/II inhibitors (PD153035 and UO126, respectively) confirmed that the upregulation of Egr1 was downstream of EGFR and ERKI/II Map kinase pathway. ChIP on chip experiments using Egr1 antibody identified 288 significantly bound promoters upon UV stimulation. Of these target genes, 40% had consensus Egr1 site in their promoters, considerably greater than that expected by chance (p < 0.005). The array binding results were validated by PCR analysis of 25 genes using DNA from conventional IP experiment. Affymetrix gene expression analysis of UV treated and control cells confirmed that a significant number of these bound promoters showed gene expression changes. Addition of siRNA to Egr1 confirmed that the gene expression changes were dependent upon Egr1 expression. Addition of EGF led to similar expression changes for nine tested genes. Proliferation and apoptosis assays confirmed that M12 cells undergo growth arrest and apoptosis following UV irradiation. Moreover, addition of EGF also promoted significant growth inhibition. These results indicate the M12 cells undergo a EGF receptor dependent apoptosis response upon UV-stimulation and that Egr1 mediates the regulation of numerous genes downstream of the EGF receptor that are associated with this response.
Keywords: UV treatment analysis
|
| |
|
| Overall design |
duplicated experiment for Affymetrix gene expression analysis and Chip-on-Chip analysis.
|
| |
|
| Contributor(s) |
Arora S, Wang Y, McClelland M, Mercola D |
| Citation(s) |
19032775 |
| |
| Submission date |
Feb 20, 2008 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Yipeng Wang |
| E-mail(s) |
ywang@sdibr.org
|
| Phone |
8585813960
|
| Organization name |
Vaccine Research Institute of San Diego
|
| Street address |
|
| City |
San Diego |
| State/province |
CA |
| ZIP/Postal code |
92121 |
| Country |
USA |
| |
|
| Platforms (3) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
| GPL6441 |
Sidney Kimmel Cancer Center Human Promotor 19K Array, v13, set-A |
| GPL6442 |
Sidney Kimmel Cancer Center Human Promotor 19K Array, v13, set-B |
|
| Samples (8)
|
| GSM265400 |
Egr1 Chip-on-Chip, M12 untreated va. UV treated, duplicate 1, SetA Array |
| GSM265401 |
Egr1 Chip-on-Chip, M12 untreated va. UV treated, duplicate 1, SetB Array |
| GSM265402 |
Egr1 Chip-on-Chip, M12 untreated vs. UV treated, duplicate 2, SetA Array |
|
| Relations |
| BioProject |
PRJNA107853 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE10585_RAW.tar |
28.7 Mb |
(http)(custom) |
TAR (of CEL, TXT) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...