Stimulation of proliferation of U138-MG glioblastoma cells by gastrin-releasing peptide in combination with agents that enhance cAMP signaling.
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.
Farias
Caroline Brunetto
CB
Cancer Research Laboratory, Academic Hospital Research Center, Porto Alegre, Brazil.
Lima
Rodrigo Cruz
RC
Lima
Luciana Otero
LO
Flores
Debora Gazzana
DG
Meurer
Luise
L
Brunetto
Algemir Lunardi
AL
Schwartsmann
Gilberto
G
Roesler
Rafael
R
D049109:Cell Proliferation / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology*; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D018004:Receptors, Bombesin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D036341:Intercellular Signaling Peptides and Proteins; D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide; D017868:Cyclic AMP-Dependent Protein Kinases