Sodium butyrate-induced differentiation of human LIM2537 colon cancer cells decreases GSK-3 beta activity and increases levels of both membrane-boundand APC/Axin/GSK-3 beta complex-associated pools of beta-catenin

Analysis of the glycogen synthase kinase-3 beta (GSK-3 beta) activity in se veral colon cancer cell lines suggested a correlation between comparatively low enzyme activity and moderate to high differentiation status. Treatment of LIM2537 cells, a poorly differentiated colon cancer cell line, with the potent differentiating agent sodium butyrate resulted in 34% reduction in GSK-3 beta activity in the treated cells (P < 0.028, n = 3). Decreases in G SK-3<beta> activity were paralleled by stabilization of cytoplasmic beta -c atenin, a hallmark of Wnt signaling. However, in contrast to Wnt signaling, expression of the beta -catenin/ TCF target genes c-myc and cyclin D1 did not appear to be increased in the sodium butyrate-treated cells. Interestin gly, expression of membrane-bound beta -catenin was increased in the sodium butyrate-treated cells. This suggests that, in the context of cellular dif ferentiation, increases in beta -catenin expression may be sequestered at t he cell membrane and suggests that a possible role of sodium butyrate in pr omoting differentiation may be via increasing the levels of beta -catenin a vailable for cell adhesion.