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J Biol Chem, Vol. 273, Issue 27, 16659-16662, July 3, 1998
From the Unité de Dynamique des Cellules Embryonnaires et
Cancéreuses (EA 1033), Centre de Biologie Cellulaire,
Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq cedex, France
We show here that nerve growth factor (NGF), the
archetypal neurotrophic factor, is able to stimulate the proliferation
of breast cancer cells (MCF-7 and MDA-MB-231 cell lines), although it
is unable to stimulate growth of normal breast epithelial cells (NBEC).
This stimulation induced cells in the G0 phase to
reenter the cell cycle, as well as shortening cell cycle duration.
Immunoblotting experiments revealed that both the two cancer cell lines
and the NBEC express high affinity (p140trk) 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. Activation of
mitogen-activated protein kinase can be detected in breast cancer cells
after 10 min of NGF stimulation, whereas no change was detected in
NBEC. These results demonstrate that NGF is a mitogenic factor for
human breast cancer cells and that it might constitute a new regulator
of breast tumor growth.
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