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Chemosensitivity linked to p73 function
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 func...
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| Published in: | Cancer cell 2003-04, Vol.3 (4), p.403-410 |
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| Main Authors: | , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c491t-f028172c327086ff1e8764350ff0a06e319cd229f1a805d9f3f768d2d4da89833 |
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| cites | cdi_FETCH-LOGICAL-c491t-f028172c327086ff1e8764350ff0a06e319cd229f1a805d9f3f768d2d4da89833 |
| container_end_page | 410 |
| container_issue | 4 |
| container_start_page | 403 |
| container_title | Cancer cell |
| container_volume | 3 |
| creator | Irwin, Meredith S Kondo, Keiichi Marin, Maria Carmen Cheng, Lynn S Hahn, William C Kaelin, William G |
| description | 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. |
| doi_str_mv | 10.1016/S1535-6108(03)00078-3 |
| format | article |
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| ispartof | Cancer cell, 2003-04, Vol.3 (4), p.403-410 |
| issn | 1535-6108 1878-3686 |
| language | eng |
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| source | BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS |
| subjects | 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, p53 - drug effects Genes, Tumor Suppressor 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 |
| title | Chemosensitivity linked to p73 function |
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