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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

3018 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)1784-1787
Aantal pagina's4
TijdschriftScience
Volume275
Nummer van het tijdschrift5307
DOI's
StatusGepubliceerd - 21 mrt. 1997
Extern gepubliceerdJa

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