[PDF][PDF] Chemosensitivity linked to p73 function

MS Irwin, K Kondo, MC Marin, LS Cheng, WC Hahn… - Cancer cell, 2003 - cell.com
MS Irwin, K Kondo, MC Marin, LS Cheng, WC Hahn, WG Kaelin
Cancer cell, 2003cell.com
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 …
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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