Chemosensitivity linked to p73 function - PubMed (original) (raw)

Chemosensitivity linked to p73 function

Meredith S Irwin et al. Cancer Cell. 2003 Apr.

Free article

Abstract

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.

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Comment in

• p53 mutations and resistance to chemotherapy: A stab in the back for p73.
  Soussi T. Soussi T. Cancer Cell. 2003 Apr;3(4):303-5. doi: 10.1016/s1535-6108(03)00081-3. Cancer Cell. 2003. PMID: 12726854 Review.

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