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.