Serum/glucocorticoid-induced protein kinase-1 facilitates androgen receptor-dependent cell survival

I Shanmugam; G Cheng; P F Terranova; J B Thrasher; C P Thomas; B Li

doi:10.1038/sj.cdd.4402227

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Serum/glucocorticoid-induced protein kinase-1 facilitates androgen receptor-dependent cell survival

Journal article

Open access

Peer reviewed

Serum/glucocorticoid-induced protein kinase-1 facilitates androgen receptor-dependent cell survival

I Shanmugam, G Cheng, P F Terranova, J B Thrasher, C P Thomas and B Li

Cell death and differentiation, Vol.14(12), pp.2085-2094

12/2007

DOI: 10.1038/sj.cdd.4402227

PMID: 17932503

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https://doi.org/10.1038/sj.cdd.4402227View

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Abstract

Androgen receptor (AR) is a critical factor in the development and progression of prostate cancer. We and others recently demonstrated that eliminating AR expression leads to apoptotic cell death in AR-positive prostate cancer cells. To understand the mechanisms of AR-dependent survival, we performed a genome-wide search for AR-regulated survival genes. We found that serum/glucocorticoid-induced protein kinase-1 (SGK-1) mRNA levels were significantly upregulated after androgen stimulation, which was confirmed to be AR dependent. Promoter analysis revealed that the AR interacted with the proximal and distal regions of the sgk1 promoter, leading to sgk-1 promoter activation after androgen stimulation. Functional assays demonstrated that SGK-1 was indispensable for the protective effect of androgens on cell death induced by serum starvation. SGK-1 overexpression not only rescued cells from AR small-interfering RNA (siRNA)-induced apoptosis, but also enhanced AR transactivation, even in the absence of androgen. Additionally, SGK-1 siRNA reduced AR transactivation, indicating a positive feedback effect of SGK-1 expression on AR-mediated gene expression and cellular survival. Taken together, our data suggest that SGK-1 is an androgen-regulated gene that plays a pivotal role in AR-dependent survival and gene expression.

Promoter Regions, Genetic

Oligonucleotide Array Sequence Analysis

Cell Survival

Humans

Receptors, Androgen - metabolism

Transcriptional Activation - drug effects

Protein-Serine-Threonine Kinases - genetics

Enzyme Activation - drug effects

Immediate-Early Proteins - metabolism

Immediate-Early Proteins - genetics

Androgens - pharmacology

Models, Biological

Cell Line, Tumor

Gene Expression Regulation, Neoplastic - drug effects

Protein-Serine-Threonine Kinases - metabolism

RNA, Small Interfering - metabolism

Details

Title: Subtitle: Serum/glucocorticoid-induced protein kinase-1 facilitates androgen receptor-dependent cell survival
Creators: I Shanmugam - Department of Urology, The University of Kansas Medical Center, Kansas City, KS 66160, USA
G Cheng
P F Terranova
J B Thrasher
C P Thomas
B Li
Resource Type: Journal article
Publication Details: Cell death and differentiation, Vol.14(12), pp.2085-2094
Publisher: England
DOI: 10.1038/sj.cdd.4402227
PMID: 17932503
ISSN: 1350-9047
eISSN: 1476-5403
Grant note: P20RR016475 / NCRR NIH HHS
Language: English
Date published: 12/2007
Academic Unit: Stead Family Department of Pediatrics; Obstetrics and Gynecology; Internal Medicine
Record Identifier: 9983986082502771

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