Breast cancer cell-associated endopeptidase EC 24.11 modulates proliferative response to bombesin.
We have investigated the production, growth and inactivation of gastrin-releasing peptide (GRP)-like peptides in human breast cancer cell lines. Radioimmunoassay detected GRP-like immunoreactivity (GRP-LI) in T47D breast cancer cells but not in the conditioned medium, indicating rapid clearance. No GRP-LI was found in the ZR-75-1 or MDA-MB-436 cells or their conditioned medium. High-performance liquid chromatography (HPLC) analysis of the GRP-LI in the T47D cells revealed a major peak, which co-eluted with GRP(18-27), and a minor more hydrophilic peak. In vitro stimulation of T47D cell growth by bombesin (BN) was enhanced to 138% of control levels (bombesin alone) by the addition of the selective endopeptidase EC 3.4.24.11 inhibitor phosphoramidon (0.1 ng ml(-1)). Fluorogenic analysis using whole cells confirmed low levels of this phosphoramidon-sensitive enzyme on the T47D cells. This enzyme, previously unreported in human breast cancer cells, significantly modulates both T47D growth and its response to BN-induced growth.
Burns
D M
DM
School of Biomedical Sciences, University of Ulster at Jordanstown, Newtownabbey, Co. Antrim, Northern Ireland.
Walker
B
B
Gray
J
J
Nelson
J
J
D001839:Bombesin / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000031:analogs & derivatives*; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis*; D015260:Neprilysin / Q000032:analysis* / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003470:Culture Media; D006020:Glycopeptides; D009363:Neoplasm Proteins; D011480:Protease Inhibitors; D019886:Gastrin-Releasing Peptide; D015260:Neprilysin; D001839:Bombesin; C008890:phosphoramidon