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

研究成果: Article査読

31 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)e136-e141
ジャーナルExperimental Dermatology
19
8
DOI
出版ステータスPublished - 2010 8月 1

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 皮膚病学

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