Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 21 March 1997:
Vol. 275. no. 5307, pp. 1787 - 1790
DOI: 10.1126/science.275.5307.1787
Prev | Table of Contents | Next

Reports

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

Patrice J. Morin, * Andrew B. Sparks, * Vladimir Korinek, Nick Barker, Hans Clevers, Bert Vogelstein, Kenneth W. Kinzler †

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 beta -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 beta -catenin that altered functionally significant phosphorylation sites. These results indicate that regulation of beta -catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or beta -catenin.

P. J. Morin and B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.
A. B. Sparks and K. W. Kinzler, Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.
V. Korinek, N. Barker, H. Clevers, Department of Immunology, University Hospital, 35008 GA, Utrecht, The Netherlands.
*   These authors contributed equally to this work.

†   To whom correspondence should be addressed.

Read the Full Text

ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)