Figure 3.

Hypoxia- and ER stress-responsive destabilization of β-catenin results from impaired production of LRP6. A, RKO or HEK293 cells were treated with 10 μg/ml TM or 1 μm TG for 8 h, and LRP6 protein level was analyzed by immunoblotting. B, HEK293 cells were transfected with vector or plasmid expressing LRP6ΔN and then subjected to TM or TG treatment as indicated. Immunoblot analysis of LRP6, LRP6ΔN, and β-catenin protein levels is shown. C, RKO or HEK293 cells were cultured under 1% O₂ for the indicated time intervals, and LRP6 protein was analyzed by immunoblotting. D, HEK293 cells transfected with vector, LRP6ΔN, or LRP6 plasmid were subjected to 1% O₂ hypoxia or normoxia for 12 h. Shown are immunoblot analyses of LRP6 and β-catenin proteins. All quantitation data represent the mean ± S.D. from three independent experiments after normalization to the values of nontreated or vector control cells. ns, not significant; *, p < 0.05; **, p < 0.01; and ***, p < 0.001 by Student's t test.