BDNF and PDE4, but not the GRPR, regulate viability of human medulloblastoma cells.
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.
Schmidt
Anna Laura
AL
Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, Rua Sarmento Leite, 2350, 90035-003, Porto Alegre, RS, Brazil.
de Farias
Caroline Brunetto
CB
Abujamra
Ana Lucia
AL
Kapczinski
Flávio
F
Schwartsmann
Gilberto
G
Brunetto
Algemir Lunardi
AL
Roesler
Rafael
R
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D001839:Bombesin / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology*; D002648:Child; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics / Q000378:metabolism*; D019886:Gastrin-Releasing Peptide / Q000235:genetics / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000378:metabolism; D006801:Humans; D008527:Medulloblastoma / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D018004:Receptors, Bombesin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020889:Rolipram / Q000378:metabolism
D000970:Antineoplastic Agents; D019208:Brain-Derived Neurotrophic Factor; D005765:Gastrointestinal Agents; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D010726:Phosphodiesterase Inhibitors; D018004:Receptors, Bombesin; D011994:Recombinant Proteins; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D019886:Gastrin-Releasing Peptide; D020813:Receptor, trkB; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram; D001839:Bombesin