A gastrin-releasing peptide receptor antagonist stimulates Neuro2a neuroblastoma cell growth: prevention by a histone deacetylase inhibitor.
Cell Biol Int. 2009 May 5;
Authors: Abujamra AL, Almeida VR, Brunetto AL, Schwartsmann G, Roesler R
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 0.1nM inhibited, whereas 100nM 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.
PMID: 19426821 [PubMed - as supplied by publisher]