|
| Status |
Public on Oct 02, 2014 |
| Title |
Expression data from immortalized and transformed WT and HGPS cell lines |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Primary skin fibroblasts from HGPS patients and an age-matched control wild-type individuals were challenged in a standard transformation assay by retroviral introduction of TERT (T), V12-HRAS (R) and SV40 large and small T antigens (S). TERT-Immortalized cell lines from the same sources were also generated.
Abstract: Advanced age and DNA damage accumulation are strong risk factors for cancer. The premature-aging disorder Hutchinson Gilford Progeria Syndrome (HGPS) provides a unique opportunity to study the interplay between DNA damage and aging-associated tumor mechanisms, since HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neo-plastic transformation. This resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells leading to inhibition of oncogenic de-differentiation. BRD4 also in-hibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals and BRD4-mediated tumor protection is clinically relevant, since a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific functions for BRD4 in tumorigenesis.
|
| |
|
| Overall design |
2 independent cell lines are included for each of the 4 groups (TERT-WT, TRS-WT, TERT-HGPS and TRS-HGPS)
|
| |
|
| Contributor(s) |
Fernandez P, Scaffidi P, Misteli T |
| Citation(s) |
25284786 |
| |
| Submission date |
Aug 19, 2014 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Patricia Fernandez Ferri |
| E-mail(s) |
patricia.fernandezferri@nih.gov
|
| Phone |
+1 301 435 3552
|
| Organization name |
NCI/NIH
|
| Street address |
41 Library Drive, B513
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
|
| Samples (8)
|
|
| Relations |
| BioProject |
PRJNA258458 |
Less...
More...