Induction of a β-catenin-LEF-1 complex by wnt-1 and transforming mutants of β-catenin (original) (raw)

• Original Paper
• Published: 04 December 1997
• Bonnee Rubinfeld1,
• Iris Albert1,
• Karine Hovanes2,
• Marian Waterman2 &
• …
• Paul Polakis1

Oncogene volume 15, pages 2833–2839 (1997)Cite this article

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Abstract

Signal transduction by β-catenin involves its post-translational stabilization and import to the nucleus where it interacts with transcription factors. Recent implications for β-catenin signaling in cancer prompted us to examine colon cancer cell lines for the expression of LEF-1, a transcription factor that binds to β-catenin. The analysis of several cell lines revealed the expression of LEF1 mRNA and a constitutive association of the LEF-1 protein with β-catenin. In contrast to the colon cells, PC12 and 293 cells did not contain a β-catenin-LEF-1 complex, even though both proteins were detected in cell lysates. In these cells, the association of endogenous LEF1 and β-catenin was induced by stimulation with the wnt-1 proto-oncogene. The complex formed following transient stimulation with wnt-1 and also persisted in cells stably expressing wnt-1. Ectopic overexpression of β-catenin in 293 cells also induced the assembly of the β-catenin-LEF-1 complex and activated gene transcription from a LEF-1-dependent promotor. Expression of mutant oncogenic forms of β-catenin identified in cancer cells resulted in higher levels of transcriptional activity. The results suggest that a cancer pathway driven by wnt-1, or mutant forms of β-catenin, may involve the formation of a persistent transcriptionally active complex of β-catenin and LEF1.

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Authors and Affiliations

1. ONYX Pharmaceuticals, 3031 Research Drive, Richmond, 94806, California, USA
   Emilio Porfiri, Bonnee Rubinfeld, Iris Albert & Paul Polakis
2. Microbiology and Molecular Genetics Departments, University of California Irvine, Irvine, 92697, California, USA
   Karine Hovanes & Marian Waterman

Authors

1. Emilio Porfiri
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2. Bonnee Rubinfeld
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3. Iris Albert
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4. Karine Hovanes
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5. Marian Waterman
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6. Paul Polakis
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Porfiri, E., Rubinfeld, B., Albert, I. et al. Induction of a β-catenin-LEF-1 complex by wnt-1 and transforming mutants of β-catenin.Oncogene 15, 2833–2839 (1997). https://doi.org/10.1038/sj.onc.1201462

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• Received: 23 May 1997
• Revised: 28 July 1997
• Accepted: 28 July 1997
• Issue Date: 04 December 1997
• DOI: https://doi.org/10.1038/sj.onc.1201462

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