Activation of β-Catenin-Tcf Signaling in Colon Cancer by Mutations in β-Catenin or APC-Reference-Cited by-同舟云学术

Activation of β-Catenin-Tcf Signaling in Colon Cancer by Mutations in β-Catenin or APC

Published:1997-03-21 Issue:5307 Volume:275 Page:1787-1790
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Morin Patrice J.¹,Sparks Andrew B.²,Korinek Vladimir³,Barker Nick³,Clevers Hans³,Vogelstein Bert¹,Kinzler Kenneth W.²

Affiliation:

1. P. J. Morin and B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.

2. A. B. Sparks and K. W. Kinzler, Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.

3. V. Korinek, N. Barker, H. Clevers, Department of Immunology, University Hospital, 35008 GA, Utrecht, The Netherlands.

Abstract

Inactivation of the adenomatous polyposis coli ( APC ) tumor suppressor gene initiates colorectal neoplasia. One of the biochemical activities associated with the APC protein is down-regulation of transcriptional activation mediated by β-catenin and T cell transcription factor 4 (Tcf-4). The protein products of mutant APC genes present in colorectal tumors were found to be defective in this activity. Furthermore, colorectal tumors with intact APC genes were found to contain activating mutations of β-catenin that altered functionally significant phosphorylation sites. These results indicate that regulation of β-catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or β-catenin.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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5. Lessons from Hereditary Colorectal Cancer

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