β-catenin knockdown inhibits pituitary adenoma cell proliferation and invasion via interfering with AKT and gelatinases expression

Pituitary adenomas are among the most prevalent forms of intrinsic brain tumors. Although most pituitary adenomas are benign, some of them may become invasive and cause significant mass effect and hormonal dysfunction. We have previously shown that beta-catenin is overexpressed in human pituitary adenomas and its level correlates to tumor grades. In the present study, we further investigated the role of beta-catenin in pituitary adenoma cell proliferation and invasion in vitro. Stable beta-catenin knockdown pituitary adenoma cell line was created by transfecting mouse growth hormone pituitary adenoma GT1.1 cells with beta-catenin shRNA plasmid. Cell proliferation and invasion were assessed using CCK-8 kit and Transwell assay, respectively. Our data demonstrated that knockdown of beta-catenin with shRNA significantly inhibited the proliferation and invasion of GT1.1 cells. In beta-catenin shRNA transfected cells, the expression of AKT, STAT3, cyclin D1 and CDK4 were significantly suppressed, which accounted for the observed growth retardation following beta-catenin shRNA transfection. Moreover, beta-catenin shRNA transfection led to a drastic reduction in MMP-2/9 secretion into the conditioned media, which might be responsible for the reduced invasiveness of beta-catenin shRNA-transfected pituitary adenoma cells. These results indicate that beta-catenin may regulate the expression of AKT, STAT3, cyclin D1, CDK4 and MMP-2/9 to promote pituitary adenoma cell proliferation and invasion.