CONCLUSION

Interferon-induced transmembrane protein 1 (IFITM1) was downregulated in neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumor (MPNST) tissues compared to that in NF1-assocaited plexiform benign tissues. Downregulation of IFITM1 is closely involved in the activation of Ras/Raf/Mek/Erk signaling pathway that is essential for tumor progression in NF1.

Treatment of interferon-γ (INF-γ) in the MPNST cells caused elevated expression of IFITM1, thereby leading to a decrease in the Ras activation (GTP-Ras) and its downstream Erk1/2 activation (phosphorylated Erk1/2). Cotreatment of INF-γ and low-dose of cisplatin and gemcitabine effectively induced cytotoxicity of the MPNST cells.

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３７ neurofibroma가 악성종양인 malignant peripheral nerve sheath tumor(MPNST) 로의 발전은 전체 환자의 10~13%에 이르고, MPNST는 NF1 환자의 주요

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３９

인터페론-감마에 의해 유도된 IFITM1의 발현량 증가는 MPNST 세포의 Ras/Raf/Mek/Erk 경로의 활성화 억제에 영향을 미치는 것을 알 수 있다.

IFITM1에 관한 본 연구의 결과가 향후 NF1 악성화 원인규명 및 치료제 개발에 기여할 수 있기를 기대한다.

--- 핵심어: 신경섬유종증 제1형 (NF1), 악성말초신경초종양(MPNST), 종양진행, IFITM1, Ras, Erk1/2, 인터페론-감마