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Ferredoxin reductase affects p53-dependent, 5-fluorouracil-induced apoptosis in colorectal cancer cells.

Nature medicine | Oct 8, 2001

http://www.ncbi.nlm.nih.gov/pubmed/11590433

Loss of p53 gene function, which occurs in most colon cancer cells, has been shown to abolish the apoptotic response to 5-fluorouracil (5-FU). To identify genes downstream of p53 that might mediate these effects, we assessed global patterns of gene expression following 5-FU treatment of isogenic cells differing only in their p53 status. The gene encoding mitochondrial ferredoxin reductase (protein, FR; gene, FDXR) was one of the few genes significantly induced by p53 after 5-FU treatment. The FR protein was localized to mitochondria and suppressed the growth of colon cancer cells when over-expressed. Targeted disruption of the FDXR gene in human colon cancer cells showed that it was essential for viability, and partial disruption of the gene resulted in decreased sensitivity to 5-FU-induced apoptosis. These data, coupled with the effects of pharmacologic inhibitors of reactive oxygen species, indicate that FR contributes to p53-mediated apoptosis through the generation of oxidative stress in mitochondria.

Pubmed ID: 11590433 RIS Download

Mesh terms: Antimetabolites, Antineoplastic | Apoptosis | Cell Division | Colorectal Neoplasms | Ferredoxin-NADP Reductase | Flow Cytometry | Fluorouracil | Gene Expression | Gene Targeting | Humans | Oxidative Stress | Recombination, Genetic | Tumor Cells, Cultured | Tumor Suppressor Protein p53

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Associated grants

  • Agency: NCI NIH HHS, Id: CA 43460
  • Agency: NIGMS NIH HHS, Id: GM 07184
  • Agency: NCI NIH HHS, Id: R37 CA043460

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