Genomic Activation of PPARG Reveals a Candidate Therapeutic Axis in Bladder Cancer
| Autor: | Ashton C. Berger, Matthew Meyerson, David J. Kwiatkowski, Craig A. Strathdee, Andrew D. Cherniack, Fujiko Duke, Laura Furst, Jonathan T. Goldstein, Juliann Shih |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Peroxisome proliferator-activated receptor gamma endocrine system diseases Peroxisome proliferator-activated receptor Biology medicine.disease_cause Article 03 medical and health sciences Cell Line Tumor Gene duplication medicine Animals Humans Molecular Targeted Therapy chemistry.chemical_classification Mutation Bladder cancer Microarray analysis techniques Gene Expression Profiling Gene Amplification nutritional and metabolic diseases Cancer Microarray Analysis medicine.disease Gene Expression Regulation Neoplastic PPAR gamma Gene expression profiling 030104 developmental biology Urinary Bladder Neoplasms Oncology chemistry Cancer research CRISPR-Cas Systems Transcriptome |
| Zdroj: | Cancer Research. 77:6987-6998 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-17-1701 |
| Popis: | The PPARG gene encoding the nuclear receptor PPARγ is activated in bladder cancer, either directly by gene amplification or mutation, or indirectly by mutation of the RXRA gene, which encodes the heterodimeric partner of PPARγ. Here, we show that activating alterations of PPARG or RXRA lead to a specific gene expression signature in bladder cancers. Reducing PPARG activity, whether by pharmacologic inhibition or genetic ablation, inhibited proliferation of PPARG-activated bladder cancer cells. Our results offer a preclinical proof of concept for PPARG as a candidate therapeutic target in bladder cancer. Cancer Res; 77(24); 6987–98. ©2017 AACR. |
| Databáze: | OpenAIRE |
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