Department of Hematology, First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China.
Cancer Biol Ther. 2013 Apr;14(4):370-7. doi: 10.4161/cbt.23718. Epub 2013 Jan 29.
Aberrant expression of the RON receptor tyrosine kinase is associated with tumor progression and carcinogenesis. The aims of this study were to determine the role and functional mechanisms of RON in Burkitt lymphoma (BL) and to document its potential as a therapeutic target.
RON expression was determined in BL cell lines by western blot analysis and examined in human lymphoma specimens by both western blotting and immunohistochemistry. The correlation between RON expression and Epstein-Barr virus (EBV) infection was investigated. Raji cells were treated with the Zt/f2 anti-RON mAb and cell viability, colony formation, apoptosis and cell cycle arrest were measured in vitro using cell proliferation assays, colony-forming assays and flow cytometry. Downregulation of RON by Zt/f2 was validated in mice bearing Raji cell xenografts.
Immunohistostaining showed a high frequency of RON (+) cells in BL tissues and RON expression strongly correlated with EBV positivity. RON downregulation significantly decreased cell proliferation and colony formation via promotion of apoptosis and cell cycle arrest in Raji cells. The in vivo study showed that RON knockdown inhibits the tumorigenic potential of Raji cells in nude mice.
RON acts as an oncogene in the carcinogenesis and progression of BL and is therefore a potential target for therapeutic intervention.
RON 受体酪氨酸激酶的异常表达与肿瘤的进展和发生有关。本研究旨在确定 RON 在伯基特淋巴瘤（BL）中的作用和功能机制，并证明其作为治疗靶点的潜力。
通过 Western blot 分析检测 BL 细胞系中的 RON 表达，并通过 Western blot 和免疫组织化学检测人淋巴瘤标本中的 RON 表达。研究了 RON 表达与 Epstein-Barr 病毒（EBV）感染之间的相关性。用 Zt/f2 抗 RON mAb 处理 Raji 细胞，并用细胞增殖测定、集落形成测定和流式细胞术测量体外细胞活力、集落形成、细胞凋亡和细胞周期停滞。在携带 Raji 细胞异种移植物的小鼠中验证了 Zt/f2 下调 RON。
免疫组化显示 BL 组织中 RON（+）细胞的频率较高，RON 表达与 EBV 阳性密切相关。RON 下调通过促进 Raji 细胞凋亡和细胞周期停滞，显著降低细胞增殖和集落形成。体内研究表明，RON 敲低抑制了裸鼠 Raji 细胞的致瘤潜能。
RON 在 BL 的发生和进展中起癌基因作用，因此是治疗干预的潜在靶点。
