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

S. D. Conzen, D. R. Brickley, C. A. Mikosz, W. Wu, A. Bogusz

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Number of pages1
JournalBreast Cancer Research and Treatment
Volume69
Issue number3
StatePublished - Dec 1 2001
Externally publishedYes

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Glucocorticoid Receptors
Glucocorticoids
Breast
Epithelial Cells
Survival
Apoptosis
Breast Neoplasms
Cell Line
Paclitaxel
serum-inducible kinase
Cell Survival
Rabbits
Drug Therapy
Antibodies
Serum
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Expression of serum and glucocorticoid-inducible kinase-1 transmits a survival signal in human mammary epithelial cells. / Conzen, S. D.; Brickley, D. R.; Mikosz, C. A.; Wu, W.; Bogusz, A.

In: Breast Cancer Research and Treatment, Vol. 69, No. 3, 01.12.2001.

Research output: Contribution to journalArticle

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