Expression of serum and glucocorticoid-inducible kinase-1 transmits a survival signal in human mammary epithelial cells

Our laboratory has demonstrated that activation of the glucocorticoid receptor (GR) in human mammary epithelial cells(hMECs) results in the transmission of a potent survival signal. We have previously shown universal GR expression in a panel of breast cancer cell lines, all of which show some degree of protection from apoptosis following GR activation in serum-free conditions. We now demonstrate that GR activation also inhibits apoptosis induced by paclitaxel chemotherapy treatment, suggesting that GR activation initiates a central survival pathway. Interestingly, ectopic expression of one of the downstream transcriptional targets of the GR in hMECs, serum and glucocorticoid-inducible kinase-1 (SGK-1), also inhibits apoptosis under these conditions. In view of the anti-apoptotic function of SGK expression in immortalized MECs, we hypothesized that SGK expression may be elevated in breast cancer cells. In order to test this hypothesis, we developed a polyclonal rabbit antibody to human SGK (DB29) and evaluated SGK expression by Western analysis of a panel of MEC lines. We find that endogenous SGK expression in malignant and non-malignant MECs exhibits an inverse correlation with the individual cell line's susceptibility to apoptosis. Taken together, these results suggest that deregulated SGK expression inhibits apoptosis in MECs, thereby contributing to the development of breast cancer by allowing inappropriate cell survival. Experiments are ongoing to determine the mechanism(s) contributing to increased SGK protein expression in breast cancer cell lines.