The proliferative response of HT-29 human colon adenocarcinoma cells to bombesin-like peptides.
Bombesin-like peptides (BLP) and their receptors are widely distributed throughout the intestine and are potential mitogens for gastrointestinal cancers. 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 of stimulation with bombesin, GRP, neuromedin B (NMB) and neuromedin C (NMC) ranging from 0.1 nM up to 1 microM. Reverse transcription polymerase chain reaction studies, revealed the presence of mRNA for NMB and for the GRP preferring receptor (GRP-R). mRNA for GRP, NMB preferring receptor (NMB-R) and bombesin receptor subtype 3 (BRS-3) were not detected. [D-Phe(6)]bombesin-(6-13)methyl ester (A1) and BIM-23127 (A2), are considered as inhibitors of binding to GRP-R and NMB-R, respectively. Surprisingly, A1 and A2 stimulated the proliferation of HT-29 cells. Moreover, in the simultaneous presence of 1 microM A1 and 0.1 microM GRP or 0.1 nM or 0.1 microM bombesin, inhibition of the proliferation was observed. Our data demonstrate that the proliferation induced by BLP in HT-29 cells is due to interaction with the GRP-R.
Cassano
G
G
Dipartimento di Fisiologia Generale ed Ambientale, Università di Bari, Via Amendola 165/A, 70126, Bari, Italy.
Resta
N
N
Gasparre
G
G
Lippe
C
C
Guanti
G
G
D001839:Bombesin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D018004:Receptors, Bombesin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010446:Peptide Fragments; D012333:RNA, Messenger; D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide; C040794:neuromedin C; D015287:Neurokinin B; C038393:neuromedin B; D001839:Bombesin