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 States. Chemotherapy has limited success in advanced disease and the effect of tamoxifen appears to require a functional estrogen-receptor (ER). Our aim was to determine whether bombesin (BBS) regulates 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-linking methods and radioligand binding assays; intracellular calcium ([Ca2+]i) was measured after BBS treatment to confirm functional status of the receptor; and the effect of BBS on cell growth was measured directly.


RESULTS
All three cell lines had a high affinity BBS receptor (Kd = 1-7 nM; molecular 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 antagonists.


CONCLUSIONS
We conclude that BBS is trophic for human breast cancers independent of ER status, and that antagonism of the BBS receptor may be a useful target for hormonal therapy in ER-negative breast cancer.
Bold
R J
RJ
Department of Surgery, University of Texas Medical Branch, Galveston 77555, USA.
Ishizuka
J
J
Yao
C Z
CZ
Townsend
C M
CM
Thompson
J C
JC
D001839:Bombesin / Q000494:pharmacology* / Q000502:physiology; D001943:Breast Neoplasms; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D018004:Receptors, Bombesin / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology*; D014407:Tumor Cells, Cultured
D018004:Receptors, Bombesin; D011960:Receptors, Estrogen; D001839:Bombesin; D002118:Calcium