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Decreased expression of neurofibromin contributes to epithelial–mesenchymal transition in neurofibromatosis type 1
Author(s) -
Arima Yoshimi,
Hayashi Hidemi,
Kamata Kanako,
Goto Takaaki M.,
Sasaki Mikako,
Kuramochi Akira,
Saya Hideyuki
Publication year - 2010
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2009.01017.x
Subject(s) - neurofibromin 1 , neurofibromatosis , epithelial–mesenchymal transition , transition (genetics) , neurofibromatosis type i , microbiology and biotechnology , cancer research , medicine , biology , pathology , genetics , gene
Please cite this paper as: Decreased expression of neurofibromin contributes to epithelial–mesenchymal transition in neurofibromatosis type 1. Experimental Dermatology 2010; 19 : e136–e141. Abstract: Plexiform and/or dermal neurofibromas are nerve sheath tumors of the peripheral nervous system that are usually present in individuals with neurofibromatosis type 1 (NF1). Neurofibromas arise from Schwann cells with biallelic inactivation of NF1 , the gene that encodes neurofibromin. This protein is responsible for regulation of the Ras‐mediated pathway, which has been shown to play a crucial role in epithelial‐to‐mesenchymal transition (EMT). EMT is a biological process that occurs during embryogenesis and wound healing and is involved in pathological processes such as organ fibrosis and cancer metastasis. However, the relationship between neurofibromin and EMT has not been elucidated. We investigated whether the EMT‐related signaling pathway was upregulated in NF1‐associated neurofibromas and Schwann cells by assessing the expression levels of the EMT‐related transcription factors Snail, Slug, Twist, ZEB1 and ZEB2. Immunohistochemical studies and quantitative reverse transcription polymerase chain reaction revealed an increase in the expression levels of EMT‐related transcription factors in neurofibroma specimens and NF1‐derived Schwann cells (sNF96.2). In addition, the silencing of NF1 by siRNA induced the expression of EMT‐related transcription factors in normal human Schwann cells and in epithelial‐like breast cancer cells. Our findings suggest that the loss of neurofibromin activated the EMT‐related signaling pathway and that the excessive mesenchymal reaction may play a key role in the development of NF1‐associated neurofibromas.