Serum- and glucocorticoid-regulated protein kinase 3 overexpression promotes tumor development and aggression in breast cancer cells.

Abstract

Serum- and glucocorticoid-regulated protein kinase 3 (SGK3) is critical for tumor survival, proliferation and invasion. In the present study we evaluated SGK3 expression in breast tissues and investigated alterations in SGK3 levels in tumor multiplication, progression and apoptosis. Tissue microarray analyses were performed to examine SGK3 expression in breast cancer samples, as well as in adjacent noncancerous and normal tissues. The pEGFP-N1-SGK3 plasmid was transfected into MDA-MB-231 cells to generate SGK3-overexpressing cells. Cell growth assays, colony formation assays, cell cycle analyses, horizontal and vertical migration tests, reverse transcription-polymerase chain reaction and western blot assays were employed to investigate the biological behavior of SGK3-overexpressing cells. SGK3 levels were significantly higher in breast cancer samples compared with adjacent noncancerous and normal tissues. Cell growth curves revealed increased proliferation and decreased apoptosis in SGK3-overexpressing cells. SGK3-overexpressing cells also demonstrated enhanced invasion and migration abilities. SGK3-overexpressing cells had high levels of an apoptosis-related gene (bcl-xl) and invasion-related genes (mmp2 and mmp9), and decreased levels of an anti-apoptosis gene (bad). Phosphorylation of GSK-3β, which is downstream in the phosphoinositide 3-kinase signaling pathway, was activated by SGK3 overexpression. β-catenin phosphorylation did not differ between the SGK3-overexpressing and non-SGK3-overexpressing cells. SGK3 overexpression induces GSK-3β phosphorylation, enhancing apoptosis- and invasion-related genes and proteins and thereby leading to tumor development and aggression in breast cancer cells.