A gastrin-releasing peptide receptor antagonist stimulates Neuro2a neuroblastoma cell growth: prevention by a histone deacetylase inhibitor.
Gastrin-releasing peptide (GRP) acts as an autocrine growth factor for neuroblastoma and other types of cancer, and its cell-surface receptor, GRPR, is overexpressed in advanced-stage human neuroblastoma. GRPR knockdown and GRPR antagonism inhibit the growth of experimental neuroblastoma. Here we show that a GRPR antagonist promotes rather than inhibits the growth of neuroblastoma cells. The GRPR antagonist, RC-3095, at 0.1 nM inhibited, whereas at 100 nM stimulated proliferation of Neuro2a murine neuroblastoma cells in vitro. The stimulatory effects were prevented by the histone deacetylase inhibitor (HDACi), sodium butyrate (NaB). Expression of GRPR mRNA in Neuro2a cells was analyzed by RT-PCR. These findings provide evidence that a GRPR antagonist can stimulate the growth of cancer cells, and suggest that GRPR might interact with epigenetic mechanisms in regulating neuroblastoma cell growth.
Cancer Research Laboratory, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, 90035-003 Porto Alegre, RS, Brazil.
Ana Lucia
AL
Abujamra
Viviane R
VR
Almeida
Algemir L
AL
Brunetto
Gilberto
G
Schwartsmann
Rafael
R
Roesler
D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology*; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D010446:Peptide Fragments; D018004:Receptors, Bombesin; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D006655:Histone Deacetylases; D001839:Bombesin