Decreased expression of neurofibromin contributes to epithelial-mesenchymal transition in neurofibromatosis type 1

Yoshimi Arima, Hidemi Hayashi, Kanako Kamata, Takaaki M. Goto, Mikako Sasaki, Akira Kuramochi, Hideyuki Saya

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
JournalExperimental Dermatology
Volume19
Issue number8
DOIs
Publication statusPublished - 2010 Aug

Fingerprint

Neurofibromin 1
Neurofibromatosis 1
Epithelial-Mesenchymal Transition
Neurofibroma
Cells
Schwann Cells
Transcription Factors
Polymerase chain reaction
Neurology
Transcription
Neurofibromatosis 1 Genes
Small Interfering RNA
Nerve Sheath Neoplasms
Nervous System Neoplasms
Tumors
Biological Phenomena
Genes
Peripheral Nervous System
Pathologic Processes
Wound Healing

Keywords

  • Epithelial-mesenchymal transition
  • Neurofibroma
  • NF1
  • Schwann cell
  • ZEB1

ASJC Scopus subject areas

  • Dermatology
  • Molecular Biology
  • Biochemistry

Cite this

Decreased expression of neurofibromin contributes to epithelial-mesenchymal transition in neurofibromatosis type 1. / Arima, Yoshimi; Hayashi, Hidemi; Kamata, Kanako; Goto, Takaaki M.; Sasaki, Mikako; Kuramochi, Akira; Saya, Hideyuki.

In: Experimental Dermatology, Vol. 19, No. 8, 08.2010.

Research output: Contribution to journalArticle

Arima, Yoshimi ; Hayashi, Hidemi ; Kamata, Kanako ; Goto, Takaaki M. ; Sasaki, Mikako ; Kuramochi, Akira ; Saya, Hideyuki. / Decreased expression of neurofibromin contributes to epithelial-mesenchymal transition in neurofibromatosis type 1. In: Experimental Dermatology. 2010 ; Vol. 19, No. 8.
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