Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC −/− Colon Carcinoma-Reference-Cited by-同舟云学术

Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC −/− Colon Carcinoma

Published:1997-03-21 Issue:5307 Volume:275 Page:1784-1787
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Korinek Vladimir¹,Barker Nick¹,Morin Patrice J.²,van Wichen Dick³,de Weger Roel³,Kinzler Kenneth W.⁴,Vogelstein Bert²,Clevers Hans¹

Affiliation:

1. V. Korinek, N. Barker, H. Clevers, Department of Immunology, University Hospital, Post Office Box B85500, 3508 GA Utrecht, Netherlands.

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

3. D. van Wichen and R. de Weger, Department of Pathology, University Hospital, 3508 GA Utrecht, Netherlands.

4. K. W. Kinzler, Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.

Abstract

The adenomatous polyposis coli (APC) tumor suppressor protein binds to β-catenin, a protein recently shown to interact with Tcf and Lef transcription factors. The gene encoding hTcf-4, a Tcf family member that is expressed in colonic epithelium, was cloned and characterized. hTcf-4 transactivates transcription only when associated with β-catenin. Nuclei of APC −/− colon carcinoma cells were found to contain a stable β-catenin-hTcf-4 complex that was constitutively active, as measured by transcription of a Tcf reporter gene. Reintroduction of APC removed β-catenin from hTcf-4 and abrogated the transcriptional transactivation. Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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