Serum- and glucocorticoid-regulated kinase 3 promotes proliferation and inhibits apoptosis of ER+ breast cancer cells

Abstract

Objective To investigate the effects of serum- and glucocorticoid-regulated kinase 3 (SGK3) on the proliferation and apoptosis of ER positive breast cancer cell lines MCF-7 and T47D. Methods Gene expression profile interactive analysis (GEPIA) was used to analyze SGK3 expression levels in BRCA (breast cancer tissue) and normal tissue in the cancer public database, the Cancer Genome Atlas (TCGA) database, and survival analysis was performed based on SGK3 levels in the BRCA patients in the TCGA database. After inducement of SGK3 overexpression in SGK3-inducible breast cancer cell lines MCF-7-Tet-On-SGK3 and T47D-Tet-On-SGK3, MTT assay was used to detect the effect of SGK3 overexpression on cell proliferation. Flow cytometry and Annexin V-FITC apoptosis detection kit were employed to detect the effect of SGK3 overexpression on cell apoptosis. Western blotting was applied to measure the changes of apoptosis-related protein molecules. After SGK3 was knocked down with SGK3 specific small interference RNA, MTT assay was adopted to detect the effect of SGK3 knockdown on the proliferation of MCF-7 cells, flow cytometry for cell apoptosis, and Western blotting for the molecular changes of apoptosis-related proteins. Results The TCGA database had a total of 1 084 BRCA samples and 492 breast control samples. Compared with the control breast tissue, the expression of SGK3 was significantly higher in BRCA. The GEPIA survival curve analysis showed that the expression level of SGK3 was negatively correlated with the overall survival (OS) and disease-free survival (DFS) of BRCA patients. In MCF-7-Tet-On-SGK3 and T47D-Tet-On-SGK3 cells, inducing SGK3 expression promoted cell proliferation and reduced the apoptosis. At molecular level, SGK3 overexpression down-regulated the expression of apoptotic proteins Bax and cleaved-PARP, and up-regulated the level of anti-apoptotic protein Bcl-2. SGK3 knockdown in MCF-7 and T47D cells inhibited cell proliferation and increased cell apoptosis. At the molecular level, knocking SGK3 down increased Bax protein level, reduced Bcl-2 level and up-regulated cleaved-PARP. Conclusion In ER+ breast cancer cells, SGK3 promotes cell proliferation and reduces apoptosis. Its high expression may be associated with poor prognosis in breast cancer patients.

Keywords

• serum- and glucocorticoid-regulated kinase 3
• breast cancer
• proliferation
• apoptosis