Abstract
PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a negative regulator of the oncogenic PI3-K/Akt signaling pathway. Loss-of-function mutations of PTEN are seen in several human solid cancers. A murine model of conditional Pten inactivation in the pancreas is described that leads to acquisition of a profound metaplastic ductal phenotype accompanied by loss of differentiated acinar units. Evidence is presented for a centroacinar cell origin of the metaplastic "neoductules." These mice also develop invasive pancreatic adenocarcinomas at a low frequency, and provide a unique in vivo platform for exploring the role of PI3-K/Akt signaling in pancreatic neoplasia.
MeSH terms
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Animals
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Cell Transformation, Neoplastic
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Disease Models, Animal
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Metaplasia / pathology
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Mice
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PTEN Phosphohydrolase
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Pancreatic Neoplasms / genetics*
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Pancreatic Neoplasms / pathology
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Protein Serine-Threonine Kinases / genetics*
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Protein Tyrosine Phosphatases / genetics*
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Protein Tyrosine Phosphatases / metabolism
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Protein-Tyrosine Kinases / genetics
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins c-akt
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Tumor Suppressor Proteins / genetics*
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Tumor Suppressor Proteins / metabolism
Substances
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Proto-Oncogene Proteins
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Tumor Suppressor Proteins
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Protein Tyrosine Phosphatases
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PTEN Phosphohydrolase
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Pten protein, mouse