BDNF and PDE4, but not the GRPR, Regulate Viability of Human Medulloblastoma Cells

• Published in: Journal of molecular neuroscience 2010-03, Vol.40 (3), p.303-310
• Main Authors: Schmidt, Anna Laura, de Farias, Caroline Brunetto, Abujamra, Ana Lucia, Kapczinski, Flávio, Schwartsmann, Gilberto, Brunetto, Algemir Lunardi, Roesler, Rafael
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - metabolism; Biomedical and Life Sciences; Biomedicine; Bombesin; Bombesin - analogs & derivatives; Bombesin - genetics; Bombesin - metabolism; Brain cancer; Brain research; Brain tumors; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Cancer therapies; Cell Biology; Cell Survival - physiology; Cells; Child; Children; Cyclic AMP; Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics; Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism; Gastrin-releasing peptide; Gastrin-Releasing Peptide - genetics; Gastrin-Releasing Peptide - metabolism; Gastrointestinal Agents - metabolism; Glioma cells; Growth factors; Humans; Immunohistochemistry; Influence; Medical research; Medulloblastoma; Medulloblastoma - metabolism; Nervous system; Neurochemistry; Neurology; Neuropeptide receptors; Neuropeptides; Neurosciences; Neurotransmitter Agents - metabolism; Neurotrophins; Peptide Fragments - metabolism; Peptides; phosphodiesterase; Phosphodiesterase Inhibitors - metabolism; Polymerase chain reaction; Proteomics; Receptor, trkB - metabolism; Receptors, Bombesin - genetics; Receptors, Bombesin - metabolism; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; RNA-directed DNA polymerase; rolipram; Rolipram - metabolism; TrkB receptors; Tumors
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-009-9221-8

Medulloblastoma is the most common brain tumor of childhood. Emerging molecular targets in medulloblastoma include neurotrophin and neuropeptide receptors. In the present study, we have examined the influence of brain-derived neurotrophic factor (BDNF)/TrkB receptor- and gastrin-releasing peptide receptor (GRPR)-mediated signaling on the viability of human medulloblastoma cells. The expression of TrkB and GRPR was confirmed by immunohistochemistry and mRNA for both BDNF and GRPR was detected by reverse transcriptase polymerase chain reaction in Daoy, D283, and ONS76 cells. Treatment with BDNF significantly inhibited the viability of Daoy and D283, but not ONS76 cells, measured with the MTT assay. Neither the GRPR agonists GRP and bombesin nor the GRPR antagonist RC-3095 affected cell viability. Because previous findings have indicated that the viability of glioma cells might be enhanced by GRP when combined with the cAMP phosphodiesterase-4 (PDE4) inhibitor rolipram, we also examined the effects of rolipram alone or combined with GRP on cell viability. Rolipram significantly reduced the viability of all three cell lines, and the inhibitory effect of rolipram in Daoy cells was not modified by cotreatment with GRP. The results suggest that BDNF/TrkB and PDE4, but not the GRPR, regulate the viability of medulloblastoma cells.