Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway. Cancer Res 2009 Mar 01;69(5):2108-16 PMID: 19244110 PMCID: PMC2746047

Pubmed ID

19244110

DOI

10.1158/0008-5472.CAN-08-3495

Abstract

We have identified RGS17 as a commonly induced gene in lung and prostate tumors. Through microarray and gene expression analysis, we show that expression of RGS17 is up-regulated in 80% of lung tumors, and also up-regulated in prostate tumors. Through knockdown and overexpression of RGS17 in tumor cells, we show that RGS17 confers a proliferative phenotype and is required for the maintenance of the proliferative potential of tumor cells. We show through exon microarray, transcript analysis, and functional assays that RGS17 promotes cyclic AMP (cAMP)-responsive element binding protein (CREB)-responsive gene expression, increases cAMP levels, and enhances forskolin-mediated cAMP production. Furthermore, inhibition of cAMP-dependent kinase prevents tumor cell proliferation, and proliferation is partially rescued by RGS17 overexpression. In the present study, we show a role for RGS17 in the maintenance of tumor cell proliferation through induction of cAMP signaling and CREB phosphorylation. The prevalence of the induction of RGS17 in tumor tissues of various types further implicates its importance in the maintenance of tumor growth.

Author List

James MA, Lu Y, Liu Y, Vikis HG, You M

Authors

Michael James PhD Assistant Professor in the Surgery department at Medical College of Wisconsin
Ming You MD, PhD Associate Provost, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




Scopus

2-s2.0-62449130006   54 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Cell Line, Tumor
Cell Proliferation
Cyclic AMP
Cyclic AMP Response Element-Binding Protein
Cyclic AMP-Dependent Protein Kinases
Humans
Lung Neoplasms
Male
Mice
Phosphorylation
Prostatic Neoplasms
RGS Proteins
Signal Transduction
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e