The proliferative response of HT-29 human colon adenocarcinoma cells to bombesin-like peptides

Bombesin-like peptides (BLP) and their receptors are widely distributed thr oughout the intestine and are potential mitogens for gastrointestinal cance rs. In this study we characterized the proliferation induced by BLP in the human adenocarcinoma cell line HT-29. The number of HT-29 cells, partially serum deprived (1% fetal bovine serum) for 48 h, was increased after 24 h o f stimulation with bombesin, GRP, neuromedin B (NMB) and neuromedin C (NMC) ranging from 0.1 nM up to 1 muM. Reverse transcription polymerase chain re action studies, revealed the presence of mRNA for NMB and for the GRP prefe rring receptor (GRP-R). mRNA for GRP, NMB preferring receptor (NMB-R) and b ombesin receptor subtype 3 (BRS-3) were not detected. [D-Phe(6)]bombesin-(6 -13)methyl ester (Al) and BIM-23127 (A2), are considered as inhibitors of b inding to GRP-R and NMB-R, respectively. Surprisingly, A I and A2 stimulate d the proliferation of HT-29 cells. Moreover, in the simultaneous presence of 1 muM Al and 0.1 muM GRP or 0.1 nM or 0.1 muM bombesin, inhibition of th e proliferation was observed. Our data demonstrate that the proliferation i nduced by BLP in HT-29 cells is due to interaction with the GR-P-R. (C) 200 1 Elsevier Science Ireland Ltd. All rights reserved.