Stimulation of proliferation of U138-MG glioblastoma cells by gastrin-releasing peptide in combination with agents that enhance cAMP signaling

被引：33

作者：

de Farias, Caroline Brunetto ^{[2
,3
,4
]}

Lima, Rodrigo Cruz ^{[1
,2
]}

Lima, Luciana Otero ^{[2
]}

Flores, Debora Gazzana ^{[1
,2
]}

Meurer, Luise ^{[5
]}

Brunetto, Algemir Lunardi ^{[2
,3
,4
]}

Schwartsmann, Gilberto ^{[2
,6
]}

Roesler, Rafael ^{[1
,2
]}

机构：

[1] Univ Fed Rio Grande do Sul, Inst Basic Hlth Sci, Dept Pharmacol, Cellular & Mol Neuropharmacol Res Grp, BR-90046900 Porto Alegre, RS, Brazil

[2] Univ Fed Rio Grande do Sul, Acad Hosp, Res Ctr, Canc Res Lab, BR-90046900 Porto Alegre, RS, Brazil

[3] Univ Fed Rio Grande do Sul, Childrens Canc Inst, BR-90046900 Porto Alegre, RS, Brazil

[4] Univ Fed Rio Grande do Sul, Pediat Oncol Unit, BR-90046900 Porto Alegre, RS, Brazil

[5] Univ Fed Rio Grande do Sul, Acad Hosp, Dept Pathol, BR-90046900 Porto Alegre, RS, Brazil

[6] Univ Fed Rio Grande do Sul, Fac Med, Dept Internal Med, BR-90046900 Porto Alegre, RS, Brazil

来源：

ONCOLOGY | 2008年 / 75卷 / 1-2期

关键词：

bombesin-like peptides; gastrin-releasing peptide receptor; cAMP signaling; glioblastoma; brain tumor;

D O I：

10.1159/000151616

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Increasing evidence indicates that gastrin-releasing peptide (GRP) acts as an autocrine growth factor for brain tumors. However, it remains unclear whether the cAMP/protein kinase A (PKA) signaling pathway plays a role in mediating the mitogenic effects of GRP. We show here that GRP combined with agents that stimulate the cAMP/PKA pathway promotes proliferation of human gliobastoma cells. Treatment with GRP combined with the adenylyl cyclase activator forskolin, the cAMP analog 8-Br-cAMP or the phosphodiesterase type IV inhibitor rolipram increased proliferation of U138-MG cells in vitro measured by MTT assay. None of the compounds had an effect when given alone. GRP receptor (GRPR) mRNA and protein expression in U138-MG cells was detected by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. The results suggest that GRP and the GRPR interact with the cAMP/PKA signaling pathway in stimulating cancer cell proliferation. Copyright (C) 2008 S. Karger AG, Basel.

引用

页码：27 / 31

页数：5

共 29 条

[1] Gq-mediated activation of c-Jun N-terminal kinase by the gastrin-releasing peptide-preferring bombesin receptor is inhibited upon costimulation of the Gs-coupled dopamine D1 receptor in COS-7 cells [J].