Bombesin stimulates in vitro growth of human breast cancer independent of estrogen receptors status

Background: Approximately 180,000 women will be found to have breast cancer this year in the United Stares. Chemotherapy has limited success in advanc ed disease and the effect of tamoxifen appears to require a functional estr ogen-receptor (ER). Our aim was to determine whether bombesin (BBS) regulat es growth of human breast cancer cells. Methods: Estrogen-dependent (MCF-7) , estrogen-responsive (ZR-75-1) and estrogen-independent (MDA-MB-231) human breast cancer cells were studied. Receptors were identified by cross-linki ng methods and radioligand binding assays; intracellular calcium ([Ca2+](i) ) was measured after BBS treatment to confirm functional status of the rece ptor; and the effect of BBS on cell growth was measured directly Results: A ll three cell lines had a high affinity BBS receptor (K-d = 1-7 nM; molecul ar weight 75 kDa). BBS stimulated [Ca2+ ](i) levels as well as cell growth in all three cell lines; the trophic effect was blocked by BBS receptor ant agonists. Conclusions: We conclude that BBS is trophic for human breast can cers independent of ER status, and that antagonism of the BBS receptor may be a useful target for hormonal therapy in ER-negative breast cancer.