Department of Pathology, Tufts University School of Medicine and New England Medical Center, Boston, Massachusetts 02111, USA
Address for correspondence: Arthur S. Tischler, M.D., Department of Pathology, New England Medical Center, Box 802, 750 Washington Street, Boston, MA 02111. Voice: 617-636-1038; fax: 617-636-8302.
atischler{at}lifespan.org
Ann. N.Y. Acad. Sci. 971: 371-378 (2002).
Adrenergic mouse pheochromocytoma (MPC) cells from heterozygous
neurofibromatosis knockout mice show little or no expression
of the NGF receptor trk A and do not undergo neuronal differentiation
in response to NGF. However, they express high levels of receptor
tyrosine kinase, Ret, and GDNF family receptor
1 (GFR
1)
in vivo and
in vitro and respond to glial cell line—derived neurotrophic
factor (GDNF). In addition, they form short processes in response
to PACAP or cyclic AMP. Morphological effects of GDNF, PACAP,
or cyclic AMP are similar to those of NGF, PACAP, or cyclic
AMP on PC12 cells, and all three agents cause downregulation
of PNMT mRNA. The MAP kinase kinase inhibitor U0126 inhibits
both baseline proliferation and stimulated process outgrowth,
consistent with a model in which sustained low-level ERK activation
drives proliferation, and more intense activation drives neuronal
differentiation. The sensitivity of MPC cells to U0126 both
may reflect mechanisms that cause pheochromocytomas in neurofibromatosis
and aid in their clarification.
