Constitutive transcriptional activation by a β-catenin-Tcf complex in APC(-/-) colon carcinoma

Vladimir Korinek, Nick Barker, Patrice J. Morin, Dick Van Wichen, Roel De Weger, Kenneth W. Kinzler, Bert Vogelstein, Hans Clevers

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1784-1787
Number of pages4
JournalScience
Volume275
Issue number5307
DOIs
StatePublished - Mar 21 1997
Externally publishedYes

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ASJC Scopus subject areas

  • General

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