Smad3 mutant mice develop metastatic colorectal cancer

Zhu Yuan; James A. Richardson; Luis F. Parada; Jonathan M. Graft

doi:10.1016/S0092-8674(00)81730-4

Smad3 mutant mice develop metastatic colorectal cancer

Zhu Yuan, James A. Richardson, Luis F. Parada, Jonathan M. Graft

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

525 Scopus citations

Abstract

TGFβ-related growth factors have been implicated in a variety of developmental and physiological processes in organisms ranging from nematodes to mammals. TGFβ transduces its signal to the interior of the cell via Smad2, Smad3, and Smad4. We report the cloning and targeted disruption of the mouse Smad3 gene. Smad3 mutant mice are viable and fertile. Between 4 and 6 months of age, the Smad3 mutant mice become moribund with colorectal adenocarcinomas. The neoplasms penetrate through the intestinal wall and metastasize to lymph nodes. These results directly implicate TGFβ signaling in the pathogenesis of colorectal cancer and provide a compelling animal model for the study of human colorectal cancer.

Original language	English (US)
Pages (from-to)	703-714
Number of pages	12
Journal	Cell
Volume	94
Issue number	6
DOIs	https://doi.org/10.1016/S0092-8674(00)81730-4
State	Published - Sep 18 1998

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/S0092-8674(00)81730-4

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@article{1b14683e4dca475abd9e22c47f2ccbd3,

title = "Smad3 mutant mice develop metastatic colorectal cancer",

abstract = "TGFβ-related growth factors have been implicated in a variety of developmental and physiological processes in organisms ranging from nematodes to mammals. TGFβ transduces its signal to the interior of the cell via Smad2, Smad3, and Smad4. We report the cloning and targeted disruption of the mouse Smad3 gene. Smad3 mutant mice are viable and fertile. Between 4 and 6 months of age, the Smad3 mutant mice become moribund with colorectal adenocarcinomas. The neoplasms penetrate through the intestinal wall and metastasize to lymph nodes. These results directly implicate TGFβ signaling in the pathogenesis of colorectal cancer and provide a compelling animal model for the study of human colorectal cancer.",

author = "Zhu Yuan and Richardson, {James A.} and Parada, {Luis F.} and Graft, {Jonathan M.}",

note = "Funding Information: We thank Mark Henkemeyer for comments and Tammy Oliver, Kim Meyers, John Shelton, and Rashmi Lalan for technical support. We thank Terry Yamaguchi, Richard Harland, Andreas Kispert, and Andy McMahon for providing reagents. J. G. acknowledges the support of Doug Melton in the cloning of mouse Smads. This work was supported by the Excellence in Education Foundation to L. F. P. ",

year = "1998",

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doi = "10.1016/S0092-8674(00)81730-4",

language = "English (US)",

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pages = "703--714",

journal = "Cell",

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publisher = "Cell Press",

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T1 - Smad3 mutant mice develop metastatic colorectal cancer

AU - Yuan, Zhu

AU - Richardson, James A.

AU - Parada, Luis F.

AU - Graft, Jonathan M.

N1 - Funding Information: We thank Mark Henkemeyer for comments and Tammy Oliver, Kim Meyers, John Shelton, and Rashmi Lalan for technical support. We thank Terry Yamaguchi, Richard Harland, Andreas Kispert, and Andy McMahon for providing reagents. J. G. acknowledges the support of Doug Melton in the cloning of mouse Smads. This work was supported by the Excellence in Education Foundation to L. F. P.

PY - 1998/9/18

Y1 - 1998/9/18

N2 - TGFβ-related growth factors have been implicated in a variety of developmental and physiological processes in organisms ranging from nematodes to mammals. TGFβ transduces its signal to the interior of the cell via Smad2, Smad3, and Smad4. We report the cloning and targeted disruption of the mouse Smad3 gene. Smad3 mutant mice are viable and fertile. Between 4 and 6 months of age, the Smad3 mutant mice become moribund with colorectal adenocarcinomas. The neoplasms penetrate through the intestinal wall and metastasize to lymph nodes. These results directly implicate TGFβ signaling in the pathogenesis of colorectal cancer and provide a compelling animal model for the study of human colorectal cancer.

AB - TGFβ-related growth factors have been implicated in a variety of developmental and physiological processes in organisms ranging from nematodes to mammals. TGFβ transduces its signal to the interior of the cell via Smad2, Smad3, and Smad4. We report the cloning and targeted disruption of the mouse Smad3 gene. Smad3 mutant mice are viable and fertile. Between 4 and 6 months of age, the Smad3 mutant mice become moribund with colorectal adenocarcinomas. The neoplasms penetrate through the intestinal wall and metastasize to lymph nodes. These results directly implicate TGFβ signaling in the pathogenesis of colorectal cancer and provide a compelling animal model for the study of human colorectal cancer.

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JO - Cell

JF - Cell

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ER -

Smad3 mutant mice develop metastatic colorectal cancer

Abstract

ASJC Scopus subject areas

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