Carcinogen-induced pancreatic lesions in the mouse: effect of Smad4 and Apc genotypes

Jan Cullingworth; Martin L Hooper; David J Harrison; John O Mason; Christian Sirard; Charles E Patek; Alan R Clarke

doi:10.1038/sj.onc.1205673

Carcinogen-induced pancreatic lesions in the mouse: effect of Smad4 and Apc genotypes

Jan Cullingworth, Martin L Hooper, David J Harrison, John O Mason, Christian Sirard, Charles E Patek, Alan R Clarke

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Mutations in the tumour suppressor genes SMAD4 (DPC4, deleted in pancreatic cancer locus 4) and adenomatous polyposis coli (APC) have been implicated in the development of pancreatic cancer in humans. Treatment of wild-type, Smad4(+/-), Apc(Min/+) or Apc(Min/+)Smad4(+/-) mice with N-Nitroso-N-Methyl Urea (NMU) results in abnormal foci in pancreatic acinar cells characterized by increased levels of beta-catenin. Previously such foci have been shown to be the precursors of pancreatic neoplasia. Interestingly, only NMU-treated Apc(Min/+)Smad4(+/-) mice exhibit a significant increase in abnormal pancreas, which was found to be due to increased number of abnormal foci rather than increased focus size. A range of foci sizes were analysed, but only smaller abnormal foci were characterized by morphological nuclear atypia. These studies suggest functional co-operation between TGF-beta and Wnt signalling pathways in the suppression of pancreatic tumorigenesis in the mouse.

Original language	English
Pages (from-to)	4696-4701
Number of pages	6
Journal	Oncogene
Volume	21
Issue number	30
DOIs	https://doi.org/10.1038/sj.onc.1205673
Publication status	Published - 2002

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title = "Carcinogen-induced pancreatic lesions in the mouse: effect of Smad4 and Apc genotypes",

abstract = "Mutations in the tumour suppressor genes SMAD4 (DPC4, deleted in pancreatic cancer locus 4) and adenomatous polyposis coli (APC) have been implicated in the development of pancreatic cancer in humans. Treatment of wild-type, Smad4(+/-), Apc(Min/+) or Apc(Min/+)Smad4(+/-) mice with N-Nitroso-N-Methyl Urea (NMU) results in abnormal foci in pancreatic acinar cells characterized by increased levels of beta-catenin. Previously such foci have been shown to be the precursors of pancreatic neoplasia. Interestingly, only NMU-treated Apc(Min/+)Smad4(+/-) mice exhibit a significant increase in abnormal pancreas, which was found to be due to increased number of abnormal foci rather than increased focus size. A range of foci sizes were analysed, but only smaller abnormal foci were characterized by morphological nuclear atypia. These studies suggest functional co-operation between TGF-beta and Wnt signalling pathways in the suppression of pancreatic tumorigenesis in the mouse.",

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AU - Cullingworth, Jan

AU - Hooper, Martin L

AU - Harrison, David J

AU - Mason, John O

AU - Sirard, Christian

AU - Patek, Charles E

AU - Clarke, Alan R

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N2 - Mutations in the tumour suppressor genes SMAD4 (DPC4, deleted in pancreatic cancer locus 4) and adenomatous polyposis coli (APC) have been implicated in the development of pancreatic cancer in humans. Treatment of wild-type, Smad4(+/-), Apc(Min/+) or Apc(Min/+)Smad4(+/-) mice with N-Nitroso-N-Methyl Urea (NMU) results in abnormal foci in pancreatic acinar cells characterized by increased levels of beta-catenin. Previously such foci have been shown to be the precursors of pancreatic neoplasia. Interestingly, only NMU-treated Apc(Min/+)Smad4(+/-) mice exhibit a significant increase in abnormal pancreas, which was found to be due to increased number of abnormal foci rather than increased focus size. A range of foci sizes were analysed, but only smaller abnormal foci were characterized by morphological nuclear atypia. These studies suggest functional co-operation between TGF-beta and Wnt signalling pathways in the suppression of pancreatic tumorigenesis in the mouse.

AB - Mutations in the tumour suppressor genes SMAD4 (DPC4, deleted in pancreatic cancer locus 4) and adenomatous polyposis coli (APC) have been implicated in the development of pancreatic cancer in humans. Treatment of wild-type, Smad4(+/-), Apc(Min/+) or Apc(Min/+)Smad4(+/-) mice with N-Nitroso-N-Methyl Urea (NMU) results in abnormal foci in pancreatic acinar cells characterized by increased levels of beta-catenin. Previously such foci have been shown to be the precursors of pancreatic neoplasia. Interestingly, only NMU-treated Apc(Min/+)Smad4(+/-) mice exhibit a significant increase in abnormal pancreas, which was found to be due to increased number of abnormal foci rather than increased focus size. A range of foci sizes were analysed, but only smaller abnormal foci were characterized by morphological nuclear atypia. These studies suggest functional co-operation between TGF-beta and Wnt signalling pathways in the suppression of pancreatic tumorigenesis in the mouse.

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JO - Oncogene

JF - Oncogene

IS - 30

ER -

Carcinogen-induced pancreatic lesions in the mouse: effect of Smad4 and Apc genotypes

Abstract

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