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| Status |
Public on Apr 01, 2018 |
| Title |
Role of histone demethylase Kdm6a in pancreatic cancer (PrimeView) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Transcriptional profile of human pancreatic cancer cell lines trerated with JQ1 inhibitor.
Loss-of-function mutations of KDM6A, an X chromosome encoded histone H3K27 demethylase, are frequent in a broad spectrum of epithelial and hematopoietic malignancies and contribute to oncogenesis with so far poorly characterized mechanisms. Pancreas specific ablation of Kdm6a in mice accelerated Kras-driven cell transformation and compromised survival in a gender specific manner. Female knockout animals were particularly vulnerable and developed aggressive squamous and quasi-mesenchymal tumors with metastatic potential, as opposed to males which developed adenocarcinomas and exhibited a better prognosis. Integration of gene expression studies coupled to ChIP-seq profiling of chromatin modifications demonstrated that loss of Kdm6a caused genome-wide remodeling of bivalent promoters and rewiring of enhancer chromatin to repress endodermal fate by activating c-MYC and TP63 dependent transcriptional programs favoring squamous and quasi-mesenchymal differentiation.
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| Overall design |
Human pancreatic cancer cell lines were treated with 500nM of JQ1 for 24 hours. Gene expression was analyzed with the Affymetrix platform to identify differentially regualted genes.
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| Contributor(s) |
Kai Y, Tzatsos A |
| Citation(s) |
29533787 |
| Submission date |
Apr 21, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Alexandros Tzatsos |
| E-mail(s) |
atzatsos@gwu.edu
|
| Phone |
2029949104
|
| Organization name |
George Washington University
|
| Department |
GW Cancer Center
|
| Lab |
Cancer Epigenetics Laboratory
|
| Street address |
800 22nd St NW SEH 8850
|
| City |
Washington |
| State/province |
DC |
| ZIP/Postal code |
20052 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL15207 |
[PrimeView] Affymetrix Human Gene Expression Array |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE98067 |
Role of histone demethylase Kdm6a in pancreatic cancer |
|
| Relations |
| BioProject |
PRJNA383873 |
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