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.