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Journal of Neuroscience, Vol 13, 1533-1542, Copyright © 1993 by Society for Neuroscience
Nerve growth factor is a potent inducer of proliferation and neuronal differentiation for adult rat chromaffin cells in vitro
AS Tischler, JC Riseberg, MA Hardenbrook and V Cherington
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111.
Adult rat chromaffin cells in vitro show a large proliferative response to
NGF, followed by neuronal differentiation. Infection of replicating
chromaffin cells with a retrovirus carrying the Escherichia coli beta-
galactosidase (beta-gal) gene demonstrates beta-gal expression in cells
that continue to multiply, that differentiate into neurons, and that become
static. The effects of NGF on proliferation and differentiation are
abolished by the protein kinase inhibitors K252a and staurosporine, and by
cholera toxin, an activator of adenylate cyclase. They are diminished, but
not abolished, by high concentrations of dexamethasone. Both cholera toxin
alone and phorbol myristate acetate (PMA), an activator of protein kinase
C, elicit small and inconsistent mitogenic responses. The responses to PMA
cannot be shown to be additive with the effects of NGF. NGF is a known
mitogen and neuritogen for chromaffin cells from neonatal rats, but has not
previously been believed to affect similarly chromaffin cells from adults.
The present findings suggest that portions of NGF signaling pathways might
continue to be involved in regulating proliferation of adult rat chromaffin
cells in vivo, and might be constitutively activated in PC12 cells and
other adrenal medullary tumors. They further suggest that rat chromaffin
cells might be propagated in vitro to obtain large numbers of sympathetic
neurons expressing normal or exogenous genes.
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