Plasticity of pheochromocytoma cell lines from neurofibromatosis knockout mice.
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 alpha(1) (GFRalpha(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.
Powers
James F
JF
Department of Pathology, Tufts University School of Medicine and New England Medical Center, Boston, Massachusetts 02111, USA.
Schelling
Kimberley H
KH
Brachold
Jaime M
JM
Tischler
Arthur S
AS
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002455:Cell Division; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017253:Neurofibromatoses / Q000235:genetics*; D009570:Nitriles / Q000494:pharmacology; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; D012333:RNA, Messenger; C113580:U 0126; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases