INDUCTION OF A BETA-CATENIN-LEF-1 COMPLEX BY WNT-1 AND TRANSFORMING MUTANTS OF BETA-CATENIN

Signal transduction by beta-catenin involves its posttranslational sta bilization and import to the nucleus where it interacts with transcrip tion factors, Recent implications for beta-catenin signaling in cancer prompted us to examine colon cancer cell lines for the expression of LEF-1, a transcription factor that binds to beta-catenin, The analysis of several cell lines revealed the expression of LEF1 mRNA and a cons titutive association of the LEF-1 protein with beta-catenin, In contra st to the colon cells, PC12 and 293 cells did not contain a beta-caten in-LEF-1 complex, even though both proteins were detected in cell lysa tes, In these cells, the association of endogenous LEF1 and beta-caten in was induced by stimulation with the wnt-1 proto-oncogene. The compl ex formed following transient stimulation with wnt-1 and also persiste d in cells stably expressing wnt-1. Ectopic overexpression of beta-cat enin in 293 cells also induced the assembly of the beta-catenin-LEF-1 complex and activated gene transcription from a LEF-1-dependent promot or, Expression of mutant oncogenic forms of beta-catenin identified in cancer cells resulted in higher levels of transcriptional activity, T he results suggest that a cancer pathway driven by wnt-1, or mutant fo rms of beta-catenin, may involve the formation of a persistent transcr iptionally active complex of beta-catenin and LEF1.