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제1형 신경섬유종증의 종양 악성화에 관여하는 IFITM1 유전자의 역할
- Alternative Title
- The role of IFITM1 in malignant progression of neurofibromas in NF1
- Author(s)
- 임규빈
- Advisor
- 김현주, 정선용
- Department
- 일반대학원 의생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2017-08
- Language
- eng
- Alternative Abstract
- Neurofibromatosis type 1 (NF1) is one of the most commonly inherited autosomal dominant human genetic disorder with an incidence of approximately 1 in 3000~3500 individuals worldwide. NF1 is caused by loss-of-function mutations in the NF1 gene encoding neurofibromin, a GTPase-activating protein. Because the pathogenesis of the tumor progression of benign plexiform neurofibromas (PNs) to malignant peripheral nerve sheath tumors (MPNSTs) remained unclear, genetic and epigenetic changes involved in MPNST pathogenesis. Here I found that interferon-induced transmembrane protein 1 (IFITM1) was downregulated in MPNST tissues compared to that in PN tissues from NF1 patients by immunohistological staining and/or Western blot analysis. Overexpression of IFITM1 in the NF1-deficient MPNST tumor cells resulted in a decrease in Ras activation (GTP-Ras), while downregulation of IFITM1 by treatment of small interfering RNA in normal-phenotypic NF1-deficient cells caused an increase in Erk1/2 activation (phosphorylated Erk1/2), indicating that expression level of IFITM1 is closely related with 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 and its downstream Erk1/2 activation. Notably, INF-γ produced a sensitization effect on enhancing cytotoxicity of MPNST cells by cotreatment of low-dose cisplatin and gemcitabine. These results provide a new potential target for chemotherapy in the NF1 patients with MPNSTs.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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