Overexpressed LEF-1 proteins display different nuclear localization patterns of β-catenin in normal versus tumor cells

β-Catenin not only plays a role in cadherin-dependent cell adhesion, but also interacts with T-cell factor (TCF)/lymphoid enhancer factor-1 (LEF-1) to affect gene expression. In this report, we describe the effects of exogenous LEF-1 and of treatment with leptomycin B (LMB), a specific inhibitor of CRM1-medicated nuclear export, on the nuclear localization and export of β-catenin. Normal epithelial cells overexpressing LEF-1 accumulate nuclear β-catenin in a LEF-1 concentration-dependent manner. Nuclear β-catenin, once imported from the cytoplasm, is rapidly removed from the nucleus. Treatment with LMB results in dramatic retention of nuclear β-catenin in normal epithelial cells transfected with LEF-1, and this effect is intensified by treatment of N-Acetyl-leucyl-leucyl-norleucinal together with LMB. Colon carcinoma cells containing an adenomatous polyposis coli mutation retain significant amounts of LEF-1 induced nuclear β-catenin considerably after the time-point when β-catenin disappears from the nuclei of LEF-1 transfected normal epithelial cells. β-Catenin binds directly to CRM1, and overexpression of CRM1 reduces nuclear β-catenin-mediated transactivation function.