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

doi:10.1126/science.275.5307.1784

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

2829 Scopus citations

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 language	English (US)
Pages (from-to)	1784-1787
Number of pages	4
Journal	Science
Volume	275
Issue number	5307
DOIs	https://doi.org/10.1126/science.275.5307.1784
State	Published - Mar 21 1997

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

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.",

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T1 - Constitutive transcriptional activation by a β-catenin-Tcf complex in APC(-/-) colon carcinoma

AU - Korinek, Vladimir

AU - Barker, Nick

AU - Morin, Patrice J.

AU - Van Wichen, Dick

AU - De Weger, Roel

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Clevers, Hans

PY - 1997/3/21

Y1 - 1997/3/21

N2 - 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.

AB - 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.

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

Abstract

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