Chemosensitivity linked to p73 function

Cancer Cell. 2003 Apr;3(4):403-10. doi: 10.1016/s1535-6108(03)00078-3.


Most chemotherapeutic agents induce DNA damage, leading to p53 accumulation and apoptosis. The factors that determine chemosensitivity in p53-defective tumor cells are poorly understood. We found that the p53 family member p73 is induced by a wide variety of chemotherapeutic drugs. Blocking p73 function with a dominant-negative mutant, siRNA, or homologous recombination led to chemoresistance of human tumor cells and engineered transformed cells, irrespective of p53 status. Mutant p53 can inactivate p73 and downregulation of mutant p53 enhanced chemosensitivity. These findings indicate that p73 is a determinant of chemotherapeutic efficacy in humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / genetics
  • Blotting, Western
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / drug effects*
  • DNA-Binding Proteins / physiology*
  • Drug Resistance, Neoplasm / genetics*
  • Embryo, Mammalian
  • Fibroblasts / physiology
  • Genes, Tumor Suppressor
  • Genes, p53 / drug effects
  • Humans
  • In Situ Nick-End Labeling
  • Mice
  • Mutation
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / drug effects*
  • Nuclear Proteins / physiology*
  • RNA, Small Interfering / metabolism
  • Tumor Cells, Cultured
  • Tumor Protein p73
  • Tumor Suppressor Proteins


  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Small Interfering
  • TP73 protein, human
  • Trp73 protein, mouse
  • Tumor Protein p73
  • Tumor Suppressor Proteins