Human Gene Set: MALONEY_RESPONSE_TO_17AAG_DN


Standard name MALONEY_RESPONSE_TO_17AAG_DN
Systematic name M1858
Brief description Down-regulated genes in A2780 cells (ovarian cancer) treated with 17AAG [PubChem=6440175], a chemical with anticancer properties.
Full description or abstract The promising antitumor activity of 17-allylamino-17-demethoxygeldanamycin (17AAG) results from inhibition of the molecular chaperone heat shock protein 90 (HSP90) and subsequent degradation of multiple oncogenic client proteins. Gene expression microarray and proteomic analysis were used to profile molecular changes in the A2780 human ovarian cancer cell line treated with 17AAG. Comparison of results with an inactive analogue and an alternative HSP90 inhibitor radicicol indicated that increased expression of HSP72, HSC70, HSP27, HSP47, and HSP90beta at the mRNA level were on-target effects of 17AAG. HSP27 protein levels were increased in tumor biopsies following treatment of patients with 17AAG. A group of MYC-regulated mRNAs was decreased by 17AAG. Of particular interest and novelty were changes in expression of chromatin-associated proteins. Expression of the heterochromatin protein 1 was increased, and expression of the histone acetyltransferase 1 and the histone arginine methyltransferase PRMT5 was decreased by 17AAG. PRMT5 was shown to be a novel HSP90-binding partner and potential client protein. Cellular protein acetylation was reduced by 17AAG, which was shown to have an antagonistic interaction on cell proliferation with the histone deacetylase inhibitor trichostatin A. This mRNA and protein expression analysis has provided new insights into the complex molecular pharmacology of 17AAG and suggested new genes and proteins that may be involved in response to the drug or be potential biomarkers of drug action.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17409432   Authors: Maloney A,Clarke PA,Naaby-Hansen S,Stein R,Koopman JO,Akpan A,Yang A,Zvelebil M,Cramer R,Stimson L,Aherne W,Banerji U,Judson I,Sharp S,Powers M,deBilly E,Salmons J,Walton M,Burlingame A,Waterfield M,Workman P
Exact source Table 1: Decreased
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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Version history 3.1: First introduced

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