具有赖氨酸650谷氨酸突变的组成型活性成纤维细胞生长因子受体3（FGFR3）增强了浆细胞恶性肿瘤对硼替佐米的敏感性。
Constitutively active FGFR3 with Lys650Glu mutation enhances bortezomib sensitivity in plasma cell malignancy.
作者信息
Otsuka Masayasu, Mizuki Masao, Fujita Jiro, Kang Sumin, Kanakura Yuzuru
机构信息
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
出版信息
Anticancer Res. 2011 Jan;31(1):113-22.
UNLABELLED
The ectopically expressed fibroblast growth factor receptor 3 (FGFR3) and its constitutively active mutations have been detected in patients with multiple myeloma (MM). This study investigated whether the cytotoxic effects of bortezomib on malignant plasma cells are associated with FGFR3 expression and the existence of mutations of FGFR3.
MATERIALS AND METHODS
Cell apoptosis assays were performed in a plasmacytoma cell line, FR4 cells and a myeloma cell line, RPMI8226 cells overexpressing wild-type FGFR3 (FGFR3(WT)) or two different mutants, FGFR3(K650E) or FGFR3(Y373C), and the induction of endoplasmic reticulum (ER) stress protein was compared between each type of cell.
RESULTS
FR4 cells with FGFR3(K650E) showed enhanced sensitivity to bortezomib together with increased induction of ER stress proteins, compared to FR4 cells with mock, FGFR3(WT) or FGFR3(Y373C). RPMI8226 cells with FGFR3(K650E) also showed enhanced bortezomib sensitivity.
CONCLUSION
This study indicated that FGFR3K650E is associated with bortezomib sensitivity in malignant plasma cells via ER stress pathways.
未标注
在多发性骨髓瘤（MM）患者中已检测到异位表达的成纤维细胞生长因子受体3（FGFR3）及其组成型活性突变。本研究调查硼替佐米对恶性浆细胞的细胞毒性作用是否与FGFR3表达及FGFR3突变的存在有关。
材料与方法
在一个浆细胞瘤细胞系FR4细胞以及一个过表达野生型FGFR3（FGFR3(WT)）或两种不同突变体FGFR3(K650E)或FGFR3(Y373C)的骨髓瘤细胞系RPMI8226细胞中进行细胞凋亡检测，并比较每种细胞类型中内质网（ER）应激蛋白的诱导情况。
结果
与转染空载体、FGFR3(WT)或FGFR3(Y373C)的FR4细胞相比，携带FGFR3(K650E)的FR4细胞对硼替佐米的敏感性增强，同时ER应激蛋白的诱导增加。携带FGFR3(K650E)的RPMI8226细胞也表现出对硼替佐米的敏感性增强。
结论
本研究表明FGFR3K650E通过ER应激途径与恶性浆细胞对硼替佐米的敏感性相关。
Zotero 插件