p73 is effective in p53-null pancreatic cancer cells resistant to wild-type TP53 gene replacement.
Novel therapies such as gene therapy are needed for the treatment of pancreatic carcinomas. Here we show that adenovirus-mediated p73 overexpression results in a strong induction of apoptosis, whereas the effect of p53 varies between different cell lines. In particular, p53-negative AsPC-1 cells are resistant to p53-mediated apoptosis. In these cells, only ectopically expressed p73 activates the proapoptotic p53 target P53AIP1, whereas phosphorylation of p53 at Ser-46, shown to regulate transcriptional activation of P53AIP1, is missing. Our findings support the use of p73 as an anticancer drug in p53-null pancreatic cancer cells that are resistant to wild-type TP53 gene replacement.
Rödicker
Florian
F
Centre for Cancer Research and Cancer Therapy, Institute of Molecular Biology, University of Essen, Medical School, D-45122 Essen, Germany.
Pützer
Brigitte M
BM
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011506:Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C414742:P53AIP1 protein, human; D011506:Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins