Human Gene Set: SAENZ_DETOX_PATHWAY_AND_CARCINOGENESIS_DN

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For the Mouse gene set with the same name, see SAENZ_DETOX_PATHWAY_AND_CARCINOGENESIS_DN

Standard name SAENZ_DETOX_PATHWAY_AND_CARCINOGENESIS_DN
Systematic name M1141
Brief description Detoxification pathway genes down-regulated in enterocytes of transgenic mice expressing SV40 T antigen.
Full description or abstract Toxic compounds such as carcinogens are removed from the body by the action of a series of detoxifying enzymes and transporters expressed in the liver and the small intestine. We have found that intestinal epithelial cells expressing the SV40 large T antigen (TAg) contain significantly lower levels of mRNAs, encoding several drug metabolizing/detoxifying enzymes and transporters compared to their non-transgenic littermates. In addition, TAg blocks the induction of these mRNAs by xenobiotics. The repression depends on an intact LXCXE motif in TAg, suggesting that inactivation of the retinoblastoma (Rb) family of tumor suppressors plays a role in the process. These results imply that a functional Rb pathway in the intestine is necessary for the expression of the detoxification system used to clear carcinogens, and suggest that loss of this tumor suppressor might alter susceptibility to chemical injury. In addition, the effect of TAg on the detoxification pathway appears to be tissue-specific, as its ectopic expression in the liver failed to suppress the P450 enzymes. The TAg-mediated suppression of drug metabolizing/detoxifying enzymes may have broad implications in the metabolism and mechanism of action of both carcinogens and prescription drugs.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17334401   Authors: Senz-Robles MT,Toma D,Cantalupo P,Zhou J,Gong H,Edwards C,Pipas JM,Xie W
Exact source Table 1
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Organism Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
Source platform MOUSE_GENE_SYMBOL
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Version history 3.1: First introduced

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