Background: Plexiform neurofibromas occur commonly in individuals with neurofibromatosis type 1 (NF1) and consist of neurofibromatous change in multiple nerve fascicles. Previously, we had observed that both plexiform neurofibromas and normal cutaneous nerves expressed Hedgehogs (Hhs), which are intercellular signaling molecules and regulate growth and patterning during embryonic development, and their receptors. In the present study, we examined the expression of Gli1, a transcription factor which mediates Hh signaling to investigate the activation of Hh signaling in plexiform neurofibromas and normal cutaneous nerves. Methods: An antihuman Gli1 antibody was used with a standard immunoperoxidase technique to determine Gli1 expression in 5 specimens of plexiform neurofibromas and 5 specimens of normal cutaneous nerves. Results: Our results showed Gli1 expression in S-100-positive tumor cells within the involved nerve fascicles in plexiform neurofibromas but not in control normal skins. Conclusions: Our findings indicate that the Hh signaling pathway is activated in plexiform neurofibromas.

Keywords:
Gli1, Hedgehog, Neurofibromatosis type 1, Plexiform neurofibroma, Schwann cell
1.
Korf BR: Neurofibromas and malignant tumors of the peripheral nerve sheath; in Friedman JM, Gutmann DH, Maccollin M, Riccardi VM (ed): Neurofibromatosis. Baltimore, Johns Hopkins University Press, 1999, pp 142–161.
2.
Dasgupta B, Gutmann DH: Neurofibromatosis 1: Closing the GAP between mice and men. Curr Opin Genet Dev 2003;13:20–27.
3.
Wetmore C: Sonic hedgehog in normal and neoplastic proliferation: Insight gained from human tumors and animal models. Curr Opin Genet Dev 2003;13:34–42.
4.
Ingham PW: Transducing Hedgehog: The story so far. Embo J 1998;17:3505–3511.
5.
Dahmane N, Lee J, Robins P, Heller P, Ruiz i Altaba A: Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours. Nature 1997;389:876–881.
6.
Endo H, Utani A, Matsumoto F, Kuroki T, Yoshimoto S, Ichinose M, Shinkai H: A possible paracrine hedgehog signalling pathway in neurofibromas from patients with neurofibromatosis type 1. Br J Dermatol 2003;148:337–341.
7.
Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D: The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 1997;278:51–57.
8.
Friedman JM, Riccardi VM: Clinical and epidemiological features; in Friedman JM, Gutmann DH, Maccollin M, Riccardi VM (ed): Neurofibromatosis. Baltimore, Johns Hopkins University Press, 1999, pp 29–86.
9.
Fan CM, Porter JA, Chiang C, Chang DT, Beachy PA, Tessier-Lavigne M: Long-range sclerotome induction by sonic hedgehog: Direct role of the amino-terminal cleavage product and modulation by the cyclic AMP signaling pathway. Cell 1995;81:457–465.
10.
Hammerschmidt M, Bitgood MJ, McMahon AP: Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo. Genes Dev 1996;10:647–658.
11.
Tong J, Hannan F, Zhu Y, Bernards A, Zhong Y: Neurofibromin regulates G protein-stimulated adenylyl cyclase activity. Nat Neurosci 2002;5:95–96.
© 2004 S. Karger AG, Basel
2004
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