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

Oncology. 2008;75(1-2):27-31. doi: 10.1159/000151616. Epub 2008 Aug 22.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Gastrin-Releasing Peptide / pharmacology*
  • Glioblastoma / metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Receptors, Bombesin / metabolism
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured


  • Intercellular Signaling Peptides and Proteins
  • Receptors, Bombesin
  • Gastrin-Releasing Peptide
  • Cyclic AMP-Dependent Protein Kinases