|
| Status |
Public on Sep 24, 2015 |
| Title |
CDK7-dependent Transcriptional Addiction in Triple-Negative Breast Cancer (Microarray) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that exhibits extremely high levels of genetic complexity and yet a relatively uniform transcriptional program. We postulate that TNBC might be highly dependent on uninterrupted transcription of a key set of genes within this gene expression program and might therefore be exceptionally sensitive to inhibitors of transcription. Utilizing a novel kinase inhibitor and CRISPR/Cas9-mediated gene editing, we show here that triple-negative but not ER/PR+ breast cancer cells are exceptionally dependent on CDK7, a transcriptional cyclin-dependent kinase. TNBC cells are unique in their dependence on this transcriptional CDK and suffer apoptotic cell death upon CDK7 inhibition. An “Achilles cluster” of TNBC-specific genes are extremely sensitive to CDK7 inhibition and frequently associated with super-enhancers. We conclude that CDK7 mediates transcriptional addiction to a vital cluster of genes in TNBC and CDK7 inhibition may be useful therapy for this challenging cancer.
|
| |
|
| Overall design |
Expression microarrays in H3K27ac in triple-negative breast cancer +/- treatment with covalent CDK7 inhibitor THZ1 treatment
|
| |
|
| Contributor(s) |
Wang Y, Kwiatkowski N, Abraham BJ, Lee TI, Zhao J, Young RA, Gray NS |
| Citation(s) |
26406377 |
| Submission date |
May 21, 2015 |
| Last update date |
Aug 23, 2018 |
| Contact name |
Richard A Young |
| E-mail(s) |
young_computation@wi.mit.edu
|
| Phone |
617-258-5219
|
| Organization name |
Whitehead Institute for Biomedical Research
|
| Lab |
Young Lab
|
| Street address |
9 Cambridge Center
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL15207 |
[PrimeView] Affymetrix Human Gene Expression Array |
|
| Samples (21)
|
|
| This SubSeries is part of SuperSeries: |
| GSE69107 |
CDK7-dependent Transcriptional Addiction in Basal-like Breast Cancer |
|
| Relations |
| BioProject |
PRJNA284577 |
Less...
More...