Activation of inositol phospholipid signaling and Ca2+ efflux in human breast cancer cells by bombesin.
Members of the bombesin-related family of peptides (BRPs) are mitogenic for a variety of cell types; however, a role for these peptides has not been previously described in human breast cancer. Early membrane receptor signal transduction mechanisms associated with bombesin action include phospholipase C-mediated inositol phospholipid hydrolysis and the elevation of cytosolic Ca2+ levels. We have investigated a potential role for BRPs in breast cancer by studying their effect on phospholipid hydrolysis, 45Ca2+ efflux, and cell growth in the human breast cancer cell line MCF-7. Bombesin stimulated a dose-dependent increase in the hydrolysis product inositol monophosphate during 1 h with a half-maximal effect around 1 nM. A transient increase in inositol trisphosphate in response to bombesin was also apparent at 2 min. Two distinct bombesin receptor antagonists inhibited this bombesin-induced phospholipid hydrolysis. Both bombesin- and gastrin-releasing peptide also stimulated a dose-related increase in inositol phosphate production in T47D cells, a different human breast cancer cell line. The efflux of 45Ca2+ from prelabeled MCF-7 cells was also stimulated by bombesin. This apparent cellular Ca2+ mobilization was partly dependent on extracellular Ca2+ and was inhibited by Ni2+. Despite this activation of putative mitogenic signaling pathways, bombesin had no effect on either proliferation or DNA synthesis in MCF-7 cells. These data implicate a functional role for BRPs in human breast cancer.
Patel
K V
KV
Department of Chemical Pathology, St. Mary's Hospital Medical School, London, United Kingdom.
Schrey
M P
MP
D001839:Bombesin / Q000032:analysis / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007328:Insulin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D007328:Insulin; D010716:Phosphatidylinositols; D001839:Bombesin; D002118:Calcium