Expression of lymphoid enhancer factor/T-cell factor proteins in colon cancer.

Molecular genetic analysis of colon cancers has established that the Wnt signaling pathway is involved in early tumor development. Mutation of midstream components can activate the pathway, making it independent of Wnt ligands and maintaining constant pressure to change target gene expression. The transcription factors that connect the pathway to target genes are members of the lymphoid enhancer factor/T-cell factor (LEF/TCF) family. The genes for two members of this family, TCF 7 and LEF 1, produce full-length forms that mediate Wnt signals and truncated dominant negative forms that limit Wnt signals and may function as growth suppressors. Results from studies of their expression in colon cancer suggests that because Wnt-linked cancers progress to malignancy, there may be a strengthening of the Wnt signal by selective expression of the activating forms of LEF/TCFs and a bias against suppressing, truncated forms.