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 bre ast cancer, the most common tumor-related cause of death in women of Wester n countries. Therefore, breast cancer therapy should be aimed at inhibition of growth factor-dependent breast cancerous cell proliferation. However, t he relative contribution of each individual factor in the development and m aintenance of the transformed phenotype is largely unknown, Were 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 facto r (EG) and insulin-like growth factor II, and are enhanced by 17 beta -estr adiol in the human breast cancer cell line MCF-7. The effect of NGF appeare d to be mediated by its trkA receptors (trkA(NGFR)), as suggested by the po tent inhibition of both MCF-7 cell proliferation and trkA(NGFR) phosphoryla tion occurring upon treatment of cultures with the selective trkA(NGFR) inh ibitor K252a. Surprisingly, the antiestrogen drug tamoxifen (TAM) inhibited NGF-induced MCF-7 cell proliferation and trkA(NGFR) phosphorylation in a c oncentration-related fashion. The effect of TAM seemed to be estrogen recep tor-independent, because the pure estrogen receptor antagonist ICI 182.780 was unable to block NGF-induced trkA(NGFR) phosphorylation. Our data underl ine the new emerging role of trkA(NGFR) in breast tumor growth, and suggest a related novel therapeutic use of TAM in breast cancer.