Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / genetics*
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adenoviridae / genetics
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Apoptosis / genetics
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Apoptosis Regulatory Proteins
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Genes, Tumor Suppressor
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Genetic Vectors / genetics
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Humans
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Pancreatic Neoplasms / genetics*
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology
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Phosphorylation
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Proteins / antagonists & inhibitors
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Proteins / physiology
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Transcriptional Activation / physiology
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Tumor Cells, Cultured
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Tumor Protein p73
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
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Tumor Suppressor Protein p53 / physiology*
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Tumor Suppressor Proteins
Substances
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Apoptosis Regulatory Proteins
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DNA-Binding Proteins
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Nuclear Proteins
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P53AIP1 protein, human
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Proteins
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TP73 protein, human
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Tumor Protein p73
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins