A. Badache et al., EXPRESSION OF KIT IN NEUROFIBROMIN-DEFICIENT HUMAN SCHWANN-CELLS - ROLE IN SCHWANN-CELL HYPERPLASIA ASSOCIATED WITH TYPE-1 NEUROFIBROMATOSIS, Oncogene, 17(6), 1998, pp. 795-800
Type 1 Neurofibromatosis (NF1) is characterized by the formation of ne
urofibromas, benign tumors composed mainly of Schwann cells, which can
turn malignant to form neurofibrosarcomas. Neurofibromin, the protein
product of the Nf1 gene, is believed to act as a tumor suppressor, ac
celerating the conversion of the oncogene Ras to its inactive form. Th
e absence of neurofibromin could therefore lead to higher Ras activity
in Schwann cells, resulting in uncontrolled growth through a cascade
of events not yet elucidated. We describe the abnormal expression of h
igh levels of the Kit tyrosine kinase receptor in both NF1-derived Sch
wann cell lines and tissue, as compared to primary Schwann cells or sc
hwannoma-derived cells. High levels of Kit expression in the neurofibr
osarcoma-derived Schwann cells correlate with a decrease in neurofibro
min expression. Using inhibitors of tyrosine kinase receptors, we foun
d that proliferation of the neurofibrosarcoma-derived cells is depende
nt: upon activation of a subclass of tyrosine-kinase receptors. The pr
oliferation of these cells is not dependent upon an autocrine loop inv
olving typical Schwann cell mitogens. Finally, the proliferation of th
e neurofibrosarcoma-derived Schwann cells can be increased by stimulat
ion with Kit ligand. These data implicate Kit as one of the components
leading to the Schwann cell hyperplasia observed in NF1.