title: Stimulation of proliferation of U138-MG glioblastoma cells by gastrin-releasing peptide in combination with agents that enhance cAMP signaling.
abstract: 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.
authors: Cancer Research Laboratory, Academic Hospital Research Center, Porto Alegre, Brazil.
authors: Caroline Brunetto
authors: CB
authors: Farias
authors: Rodrigo Cruz
authors: RC
authors: Lima
authors: Luciana Otero
authors: LO
authors: Lima
authors: Debora Gazzana
authors: DG
authors: Flores
authors: Luise
authors: L
authors: Meurer
authors: Algemir Lunardi
authors: AL
authors: Brunetto
authors: Gilberto
authors: G
authors: Schwartsmann
authors: Rafael
authors: R
authors: Roesler
mesh_terms: 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
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide; D017868:Cyclic AMP-Dependent Protein Kinases