Human Gene Set: MANN_RESPONSE_TO_AMIFOSTINE_UP


Standard name MANN_RESPONSE_TO_AMIFOSTINE_UP
Systematic name M18954
Brief description Genes up-regulated in HCT116 cells (colon cancer) after treatment with amifostine [PubChem=2141] depending on the presence of TP53 [GeneID=7157]: TP53-positive vs TP53-null cells.
Full description or abstract The aminothiol WR1065 exerts selective cytoprotective effects in normal cells compared to cancer cells and has clinical applications for the protection of normal cells in cancer patients undergoing radio- or chemotherapy. There is evidence that p53 is activated in response to WR1065. To examine the effects of WR1065 on the signalling pathways controlled by p53, isogeneic human colon carcinoma cell lines (HCT116) differing only in the presence or absence of wild-type p53 were used. Treatment with WR1065 resulted in G1 cell cycle arrest in the p53-positive cell line but not in the p53-negative cell line. Long-term exposure resulted in minimal apoptosis of either cell line. Changes in gene expression in p53-positive or -negative cells treated with WR1065 were examined using commercial human stress and cancer gene arrays (Clontech Atlas arrays). Genes found to be specifically upregulated in a p53-dependent manner included coproporphyrinogen oxidase, ICErel-II cysteine protease, macrophage inhibitory cytokine-1 (also known as placental transforming growth factor beta), S100A4, and Waf1/p21. However, most proapoptotic genes typically upregulated by p53 in response to DNA damage were not activated. These studies show that WR1065 specifically modulates a subset of p53 target genes in a colon carcinoma cell line, consistent with the observation that this agent elicits essentially p53-dependent, cell cycle arrest responses.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15750621   Authors: Mann K,Hainaut P
Exact source Table 1, 2
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Source species Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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Version history 3.0: First introduced

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