Tamoxifen inhibits nerve growth factor-induced proliferation of the human breast cancerous cell line MCF-7.
An array of polypeptide growth factors contribute to the development of breast cancer, the most common tumor-related cause of death in women of Western countries. Therefore, breast cancer therapy should be aimed at inhibition of growth factor-dependent breast cancerous cell proliferation. However, the relative contribution of each individual factor in the development and maintenance of the transformed phenotype is largely unknown. Here we report for the first time that the proliferative effects of nerve growth factor, (NGF) a typical neurotrophin, are similar to those of epidermal growth factor (EGF) and insulin-like growth factor II, and are enhanced by 17beta-estradiol in the human breast cancer cell line MCF-7. The effect of NGF appeared to be mediated by its trkA receptors (trkA(NGFR)), as suggested by the potent inhibition of both MCF-7 cell proliferation and trkA(NGFR) phosphorylation occurring upon treatment of cultures with the selective trkA(NGFR) inhibitor K252a. Surprisingly, the antiestrogen drug tamoxifen (TAM) inhibited NGF-induced MCF-7 cell proliferation and trkA(NGFR) phosphorylation in a concentration-related fashion. The effect of TAM seemed to be estrogen receptor-independent, because the pure estrogen receptor antagonist ICI 182.780 was unable to block NGF-induced trkA(NGFR) phosphorylation. Our data underline the new emerging role of trkA(NGFR) in breast tumor growth, and suggest a related novel therapeutic use of TAM in breast cancer.
Chiarenza
A
A
Department of Experimental and Clinical Pharmacology, University of Catania School of Medicine, Italy.
Lazarovici
P
P
Lempereur
L
L
Cantarella
G
G
Bianchi
A
A
Bernardini
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D000077267:Fulvestrant; D006801:Humans; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020917:Receptor, trkA / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D020847:Estrogen Receptor Modulators; D012333:RNA, Messenger; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; D020932:Nerve Growth Factor; D020917:Receptor, trkA