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