NERVE GROWTH-FACTOR IS MITOGENIC FOR CANCEROUS BUT NOT NORMAL HUMAN BREAST EPITHELIAL-CELLS

We show here that nerve growth factor (NGF), the archetypal neurotroph ic factor, is able to stimulate the proliferation of breast cancer cel ls (MCF-7 and MDA-MB-231 cell lines), although it is unable to stimula te growth of normal breast epithelial cells (NBEC), This stimulation i nduced cells in the G(0) phase to reenter the cell cycle, as well as s hortening cell cycle duration. Immunoblotting experiments revealed tha t both the two cancer cell lines and the NBEC express high affinity (p 140(trk)) and low affinity (p75) NGF receptors. Inhibition of the NGF growth-promoting effect by the drugs K-252a and PD98059 indicated that activation of Trk-tyrosine kinase activity and the mitogen-activated protein kinase cascade are necessary to obtain the mitogenic effect. A ctivation of mitogen-activated protein kinase can be detected in breas t cancer cells after 10 min of NGF stimulation, whereas no change was detected in NBEC. These results demonstrate that NGF is a mitogenic fa ctor for human breast cancer cells and that it might constitute a new regulator of breast tumor growth.