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| Status |
Public on Oct 02, 2014 |
| Title |
Expression data from transformed WT and HGPS cell lines, including HGPS cells after knock-down of BRD4 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Primary skin fibroblasts from a HGPS patient and an age-matched control wild-type individual were challenged in a standard transformation assay by retroviral introduction of TERT (T), V12-HRAS (R) and SV40 large and small T antigens (S). Knock-down of BRD4 in this TRS-HGPS cell line (TRS-HGPS-shBRD4) was achieved by retroviral introduction of independent shRNAs (shBRD4-1 to -3)
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.
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| Overall design |
2 biological replicates are included for TRS-WT and TRS-HGPS cell lines. 3 biological replicates are included for TRS-HGPS-shBRD4 (derived from 3 independent shRNAs against BRD4)
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| Contributor(s) |
Fernandez P, Scaffidi P, Misteli T |
| Citation(s) |
25284786 |
| |
| Submission date |
Aug 19, 2014 |
| Last update date |
Aug 23, 2018 |
| 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 |
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| Platforms (1) |
| GPL15207 |
[PrimeView] Affymetrix Human Gene Expression Array |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA258457 |
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