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Series GSE60518 Query DataSets for GSE60518
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
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)
GSM1481576 TERT-WT1
GSM1481577 TRS-WT1
GSM1481578 TERT-WT2
BioProject PRJNA258458

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Supplementary file Size Download File type/resource
GSE60518_RAW.tar 43.9 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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