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[Cancer Research 61, 3002-3008, April 1, 2001]
© 2001 American Association for Cancer Research

Experimental Therapeutics

Tamoxifen Inhibits Nerve Growth Factor-induced Proliferation of the Human Breast Cancerous Cell Line MCF-71

Andrea Chiarenza2, Philip Lazarovici2, Laurence Lempereur, Giuseppina Cantarella, Alfredo Bianchi and Renato Bernardini3

Department of Experimental and Clinical Pharmacology, University of Catania School of Medicine, I-95125 Catania, Italy [A. C., L. L., G. C., A. B., R. B.], and Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel [P. L.]

ABSTRACT

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 17ß-estradiol in the human breast cancer cell line MCF-7. The effect of NGF appeared to be mediated by its trkA receptors (trkANGFR), as suggested by the potent inhibition of both MCF-7 cell proliferation and trkANGFR phosphorylation occurring upon treatment of cultures with the selective trkANGFR inhibitor K252a. Surprisingly, the antiestrogen drug tamoxifen (TAM) inhibited NGF-induced MCF-7 cell proliferation and trkANGFR 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 trkANGFR phosphorylation. Our data underline the new emerging role of trkANGFR in breast tumor growth, and suggest a related novel therapeutic use of TAM in breast cancer.




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Molecular Cancer Research Cancer Prevention Research
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Copyright © 2001 by the American Association for Cancer Research.