Potential Role for NGF in Breast Cancer

Figure 1. NGF stimulates breast cancer cell proliferation through the tyrosine kinase activity of TrkA and the MAP-kinase pathway.

Nerve growth factor (NGF) is well known for its neurotrophic activity on central as well as peripheral neuronal cells.¹ This biological activity is mediated through a specific tyrosine kinase receptor (TrkA) in conjunction with an accessory receptor named p75. The function of p75 is still controversial, but it does not involve tyrosine kinase activity (for a review, see reference 2). Biological activities other than neurotrophism have been reported for NGF, including stimulation of chemotaxis for melanocytes³ and Schwann cells,⁴ and stimulation of mitogenesis for keratinocytes.⁵

Descamps et al.⁶ demonstrated that NGF is a strong stimulator of breast cancer cell proliferation. This mitogenic effect appears to be mediated through the tyrosine kinase activity of TrkA and subsequently through the MAP-kinase pathway. Although non-cancerous breast epithelial cells also express TrkA receptors, they are not stimulated by NGF. There is no explanation for the differential effect of NGF on normal and cancerous breast cells, but the results of this study suggest that NGF plays a specific role in the initiation and progression of breast cancer. Further study of the effect(s) of NGF on breast epithelial cells may present new insights and opportunities for the understanding and the treatment of breast cancer, one of the most prevalent and lethal human pathologies.

References

1. Lewin, G.R. and Y.A. Barde (1996) Annu. Rev. Neurosci. 19:289.
2. Bradshaw, R.A. and H. Hondermarck (1996) Biomembranes 6:177.
3. Yaar, M. et al. (1991) J. Cell Biol. 115:821.
4. Anton, E.S. et al. (1994) Proc. Natl. Acad. Sci. USA 91:2795.
5. Di Marco, E. et al. (1993) J. Biol. Chem. 268:22838.
6. Descamps, S. et al. (1998) J. Biol. Chem. 273:16659.