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Chemosensitivity linked to p73 function.

机译:化学敏感性与p73功能有关。

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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.
机译:大多数化学治疗剂诱导DNA损伤,导致p53积累和凋亡。对p53缺陷肿瘤细胞化学敏感性的决定因素了解甚少。我们发现p53家族成员p73由多种化疗药物诱导。用显性阴性突变体,siRNA或同源重组阻断p73功能,无论p53处于何种状态,都可导致人肿瘤细胞和工程改造细胞的化学耐药性。突变体p53可以使p73失活,而突变体p53的下调可增强化学敏感性。这些发现表明p73是人类化学疗法疗效的决定因素。

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