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Originally published In Press as doi:10.1074/jbc.M010842200 on February 13, 2001

J. Biol. Chem., Vol. 276, Issue 20, 16649-16654, May 18, 2001
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Glucocorticoid Receptor-mediated Protection from Apoptosis Is Associated with Induction of the Serine/Threonine Survival Kinase Gene, sgk-1*

Christina A. Mikosz, Deanna R. Brickley, Melinda S. Sharkey, Timothy W. Moran, and Suzanne D. ConzenDagger

From the Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, Illinois 60637

We previously demonstrated that activation of the glucocorticoid receptor (GR) initiates an antiapoptotic signal in the immortalized human mammary epithelial cell line MCF10A that is dependent on the GR's transcriptional activity. In this study, we show that the survival role of GR activation extends to protecting human breast cancer cells undergoing apoptosis after growth factor deprivation. Serum and glucocorticoid-regulated kinase-1 (sgk), a gene previously identified as a direct transcriptional target of the activated GR in a rat mammary tumor cell line, was rapidly induced after GR activation in human mammary epithelial cells. Furthermore, in the absence of all growth factors, ectopic sgk expression inhibited apoptosis, suggesting that SGK is a survival kinase. Finally, kinase-dead SGK expression inhibited the protection from apoptosis usually seen after GR activation. These findings suggest that SGK is an important downstream target of GR-mediated survival signaling and that it is distinct from other survival kinases because it can be primarily regulated at the level of transcription.


* This work was supported in part by National Institutes of Health Grant R21 CA66132 (NCI), The National Women's Cancer Research Alliance, a Cancer Research Foundation Young Investigator's Award (to S. D. C.), and The Susan G. Komen Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Medicine, University of Chicago, 5841 South Maryland Ave., MC 2115, Chicago IL 60637. Tel.: 773-834-2604; Fax: 773-834-0188; E-mail: sconzen@medicine.bsd.uchicago.edu.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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