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| Status |
Public on Sep 18, 2015 |
| Title |
Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
Glucocorticoids (GC) have been widely used as coadjuvants in the treatment of solid tumors, but GC treatment may be associated with poor pharmacotherapeutic response and/or prognosis. The genomic action of GC in these tumors is largely unknown. Here we find that dexamethasone (Dex, a synthetic GC) regulated genes in triple-negative breast cancer (TNBC) cells are associated with drug resistance. Importantly, these GC-regulated genes are aberrantly expressed in TNBC patients and associated with unfavorable clinical outcomes. Interestingly, in TNBC cells, Compound A (CpdA, a selective GR modulator) only regulates a small number of genes not involved in carcinogenesis and therapy resistance. Mechanistic studies using a ChIP-exo approach reveal that Dex- but not CpdA-liganded glucocorticoid receptor (GR) binds to a single glucocorticoid response element (GRE), which drives the expression of pro-tumorigenic genes. Our data suggest that development of safe coadjuvant therapy should consider the distinct genomic function between Dex- and CpdA-liganded GR.
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| |
|
| Overall design |
To study GR-regulated genes and define GRE in human genome, RNA-seq and GR ChIP-exo are performed in MDA-MB-231 cells before/after dex and CpdA stimulation. Each experiment includes two replicates.
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| |
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| Contributor(s) |
Wang Q, Chen Z |
| Citation(s) |
26374485 |
| |
| Submission date |
Mar 19, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Xun Lan |
| E-mail(s) |
xlan@stanford.edu
|
| Phone |
7738345917
|
| Organization name |
Stanford University
|
| Department |
Genetics
|
| Lab |
Pritchard's Lab
|
| Street address |
318 Campus Dr. Room S240
|
| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (22)
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| Relations |
| BioProject |
PRJNA242236 |
| SRA |
SRP040300 |
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