Human Gene Set: YAGUE_PRETUMOR_DRUG_RESISTANCE_DN


Standard name YAGUE_PRETUMOR_DRUG_RESISTANCE_DN
Systematic name M2070
Brief description Down-regulated genes common to all pretumorigenic cells with acquired drug resistance.
Full description or abstract Resistance to chemotherapy is one of the principal causes of cancer mortality and is generally considered a late event in tumor progression. Although cellular models of drug resistance have been useful in identifying the molecules responsible for conferring drug resistance, most of these cellular models are derived from cell lines isolated from patients at a late stage in cancer progression. To ask at which stage in the tumorigenic progression does the cell gain the ability to acquire drug resistance, we generated a series of pre-tumorigenic and tumorigenic cells from human embryonic skin fibroblasts by introducing, sequentially, the catalytic subunit of telomerase, SV40 large T and small T oncoproteins, and an oncogenic form of ras. We show that the ability to acquire multidrug resistance (MDR) can arise before the malignant transformation stage. The minimal set of changes necessary to obtain pre-tumorigenic drug-resistant cells is expression of telomerase and inactivation of p53 and pRb. Thus, the pathways inactivated during tumorigenesis also confer the ability to acquire drug resistance. Microarray and functional studies of drug-resistant pre-tumorigenic cells indicate that the drug efflux pump P-glycoprotein is responsible for the MDR phenotype in this pre-tumorigenic cell model.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17283147   Authors: YagŁe E,Arance A,Kubitza L,O'Hare M,Jat P,Ogilvie CM,Hart IR,Higgins CF,Raguz S
Exact source Table 2: Down-regulated in resistant cells
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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