Fig. 4. Effect of -secretase inhibition on basal and BFT-induced cell proliferation. Cell proliferation in parental HT29/C1 cells and TCF dominant negative HT29/C1 cells (HT29/C1::TcfN31). Cell lines were treated with BFT (5 nM) alone or in the presence of the -secretase inhibitor, L685,458 (1.5 µM). Results are depicted as changes in the percentage uptake of [³H]thymidine compared with control cells for each cell line. BFT induces a significant increase in HT29/C1 cell proliferation in both parental and TCF dominant negative HT29/C1 cell lines (lanes 1 or 4, P<0.001 for both cell lines vs. control) that is unaltered by L685,458 (comparisons lanes 1 vs 3 and lanes 4 vs 6, P=NS). By contrast, L685,458 inhibits parental HT29/C1 cell proliferation (lane 2, P<0.001) that is ablated in TCF dominant negative HT29/C1 cells (lane 5, P<0.01 compared with lane 2) indicating -secretase regulation of parental HT29/C1 cell proliferation is dependent on -catenin/TCF nuclear signaling. Data are means ± s.d. of 3-4 experiments conducted with 3-5 replicates per experiment.