E-GEOD-50010 - Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXR-gamma activation

Status
Released on 22 October 2013, last updated on 3 June 2014
Organism
Homo sapiens
Samples (8)
Array (1)
Protocols (7)
Description
Tumor metastasis and lack of NKG2D ligand (NKG2DL) expression are associated with poor prognosis in patients with colon cancer. Here we found that spironolactone (SPIR), an FDA-approved diuretic drug with a long-term safety profile, can upregulate NKG2DL expression in multiple colon cancer cell lines by activating the ATM-Chk2-mediated checkpoint pathway, which in turn enhances tumor elimination by natural killer cells. SPIR can also upregulate the expression of metastasis-suppressor genes TIMP2 and TIMP3, thereby reducing tumor cell invasiveness. Although SPIR is an aldosterone antagonist, its anti-tumor effects are independent of the mineralocorticoid receptor pathway. Instead, by screening the human nuclear hormone receptor siRNA library, we identify retinoid X receptor gamma (RXR gamma) as being indispensable for the anti-tumor functions of SPIR. Collectively, our results strongly support the use of SPIR or other RXR gamma-agonists with minimal side effects for colon cancer prevention and therapy. Two replicates of two cell types with and without drug
Experiment type
transcription profiling by array 
Contacts
David Finkelstein <david.finkelstein@stjude.org>, Laura Janke, Queenie P Vong, Taosheng Chen, Wai-Hang Leung, Wenwei Lin, Wing Leung
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-50010.idf.txt
Sample and data relationshipE-GEOD-50010.sdrf.txt
Raw data (1)E-GEOD-50010.raw.1.zip
Processed data (1)E-GEOD-50010.processed.1.zip
Array designA-GEOD-13158.adf.txt
Links