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Stem Cells, Vol. 18, No. 5, 386-387, September 2000
© 2000 AlphaMed Press


Fundamentals of Cancer Medicine

Potential Role for NGF in Breast Cancer

Hubert Hondermarck

R&D Systems, Inc., Minneapolis, Minnesota, USA

Correspondence: Hubert Hondermarck, Ph.D, in care of Jennifer Harrington, Ph.D, R&D Systems, Inc., 614 McKinley Place NE, Minneapolis, Minnesota 55413, USA. Telephone: 612-379-2956; Fax: 612-379-6580; e-mail: info{at}rndsystems.com Website:http://www.rndsystems.com

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 [2]. Biological activities other than neurotrophism have been reported for NGF, including stimulation of chemotaxis for melanocytes [3] 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.



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

 
References

  1. Lewin GR, Barde YA. Physiology of the neurotrophins. Annu Rev Neurosci 1996;19:289-317.[CrossRef][Medline]

  2. Bradshaw RA, Hondermarck H. Nerve growth factor receptors. Biomembranes 1996;6:177-196.

  3. Yaar M, Grossman K, Eller M et al. Evidence for nerve growth factor-mediated paracrine effects in human epidermis. J Cell Biol 1991;115:821-828.[Abstract/Free Full Text]

  4. Anton ES, Weskamp G, Reichandt LF et al. Nerve growth factor and its low-affinity receptor promote Schwann cell migration. Proc Natl Acad Sci USA 1194;91:2795-2799.[Abstract/Free Full Text]

  5. Di Marco E, Mather M, Bondanza S et al. Nerve growth factor binds to normal human keratinocytes through high and low affinity receptors and stimulates their growth by a novel autocrine loop. J Biol Chem 1993;268:22838-22846.[Abstract/Free Full Text]

  6. Descamps S, Lebourhis X, Delehedde M et al. Nerve growth factor is mitogenic for cancerous but not normal human breast epithelial cells. J Biol Chem 1998;273:16659-16662.[Abstract/Free Full Text]





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