Signaling crosstalk of Galectin-3, β-catenin, and estrogen receptor in androgen-independent prostate cancer DU-145 cells.

Abstract

The aims of this study were to investigate the localization of non-phosphorylated β‑catenin and Galectin-3 (GAL-3), the regulation of the expression of both proteins by activation of estrogen receptors (ERs) and their role in tumorigenic characteristics of androgen-independent prostate cancer DU-145 cells. DU-145 cells were cultured in the absence (control), and presence of 17β-estradiol (E2). Cells were also untreated or pre-treated with the inhibitor of GAL‑3, VA03, or with a compound that disrupts the complex β-catenin-TCF/LEF transcription factor, PKF 118-310. Immunofluorescence assay for non-phosphorylated β-catenin and GAL-3, cell proliferation, wound healing and cell invasion assays were performed. 17β-estradiol (E2, 4 h) increased the expression of non-phosphorylated β-catenin and GAL-3. E2 also increased (2-fold) the co-localization of the fluorescence of non-phosphorylated β-catenin and GAL‑3 in the whole cells compared to the control. The up-regulation of non-phosphorylated β-catenin expression was blocked by VA03, suggesting that GAL-3 is upstream protein involved in this process. E2 (24 h) increased the cell number, migration, and invasion of the DU‑145 cells compared to control. Furthermore, PKF 118-310 completely blocked the proliferation, migration, and invasion of the DU-145 cells induced by activation of ERs. The activation of ERs increases the expression, co-localization and signaling of the GAL-3 and non-phosphorylated β-catenin in DU-145 cells. Non-phosphorylated β-catenin is downstream protein involved in proliferation, migration, and invasion of the DU‑145 cells.