Stimulation by bombesin and inhibition by bombesin/gastrin-releasing peptide antagonist RC-3095 of growth of human breast cancer cell lines.
Recently, it was reported that bombesin/gastrin-releasing peptide (GRP) have mitogenic effects on some human breast cancer cell lines. In this study, we investigated the effects of bombesin/GRP and its receptor antagonist (RC-3095) on the proliferation of three breast cancer cell lines, MDA-MB-231, MCF-7 MIII, and MCF-7. Stimulation by bombesin and inhibition by RC-3095 of cell growth were found in MDA-MB-231 and MCF-7 MIII cells cultured in phenol red-free medium with 5% heat-inactivated and dextran-coated charcoal-treated fetal bovine serum (DCC-FBS). A stimulatory effect by bombesin was not observed in the presence of untreated FBS. [3H]Thymidine incorporation into DNA in these cells was suppressed by RC-3095. MCF-7 cells failed to respond to bombesin and RC-3095 in the presence of either FBS or DCC-FBS. GRP-like immunoreactivity was found in the cell extracts and FBS, but it was undetectable in DCC-FBS. It appears that the stimulatory effect of bombesin on cell proliferation of MCF-7 MIII and MDA-MB-231 cell lines could be obtained because of reduction in the levels of some serum factors in DCC-FBS. These results suggest that bombesin/GRP can act as growth factors through bombesin/GRP receptors in some human breast cancers.
Yano
T
T
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana 70146.
Pinski
J
J
Groot
K
K
Schally
A V
AV
D001839:Bombesin / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000032:analysis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004967:Estrogens; D010446:Peptide Fragments; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D001839:Bombesin