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| 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
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| 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.
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| Overall design |
2 independent cell lines are included for each of the 4 groups (TERT-WT, TRS-WT, TERT-HGPS and TRS-HGPS)
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| Contributor(s) |
Fernandez P, Scaffidi P, Misteli T |
| Citation(s) |
25284786 |
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| Submission date |
Aug 19, 2014 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Patricia Fernandez Ferri |
| E-mail(s) |
[email protected]
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| Phone |
+1 301 435 3552
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| Organization name |
NCI/NIH
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| Street address |
41 Library Drive, B513
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA258458 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE60518_RAW.tar |
43.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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