RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway.
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.
James
Michael A
MA
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Lu
Yan
Y
Liu
Yan
Y
Vikis
Haris G
HG
You
Ming
M
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology*; D008297:Male; D051379:Mice; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000473:pathology*; D020710:RGS Proteins / Q000032:analysis / Q000502:physiology*; D015398:Signal Transduction
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D020710:RGS Proteins; C532880:RGS17 protein, mouse; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases