Receptor for advanced glycation end products (RAGE) partially mediates HMGB1-ERKs activation in clear cell renal cell carcinoma
Receptor for advanced glycation end products (RAGE) partially mediates HMGB1-ERKs activation in clear cell renal cell carcinoma
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DOI：
10.1007/s00432-011-1067-0
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发表时间：
2012-01-01
影响因子：
3.6
通讯作者：
Ding, Guodong
中科院分区：
文献类型：
--
作者：
Lin, Liguo;Zhong, Kaihua;Ding, Guodong
目的探讨晚期糖基化终产物受体（RAGE）和高迁移率组盒-1 （HMGB1）的表达及其在透明细胞肾细胞癌（CCRCC）发生发展中的作用。方法采用组织芯片检测RCC组织中RAGE和HMGB1的表达。在体外，用HMGB1处理静止或rage减少的RCC细胞，收集后通过Western blot检测ERK1/2磷酸化。进一步采用Ki-67免疫染色法、创面愈合法和基质侵袭法评价细胞增殖、迁移和侵袭。结果(1)RAGE、HMGB1在CCRCC中共表达升高与患者肿瘤大小、核Fuhrman分级、临床分期等临床参数呈正相关。(2)HMGB1孵育诱导ERK1/2的激活具有时间和剂量依赖性，可被U0126 （MEK1/2抑制剂）完全阻断，并可被RAGE敲除部分逆转。(3)RAGE的下调部分逆转了HMGB1对细胞增殖、迁移和侵袭的促进作用。结论HMGB1通过ERK1/2的激活促进CCRCC的发生进展，而ERK1/2的激活部分受RAGE介导。
Purpose To explore the expression of receptor for advanced glycation end products (RAGE) and high-mobility group box-1 (HMGB1) and their role in clear cell renal cell carcinoma (CCRCC) development and progression. Methods Expression of RAGE and HMGB1 was examined in RCC using tissue microarrays. In vitro, quiescent or RAGE-reduced RCC cells were subjected to treatment with HMGB1 and harvested for detecting ERK1/2 phosphorylation via Western blot. Further cell proliferation, migration and invasion were evaluated by Ki-67 immunostaining, wound healing and matrigel invasion assay, respectively. Results (1)Elevated co-expression of RAGE and HMGB1 in CCRCC was correlated positively with patients' clinical parameters including tumor size, nuclear Fuhrman grade and clinical stage. (2)HMGB1 incubation induced ERK1/2 activation in a time-and dose-dependent manner, which could be completely blocked by U0126 (MEK1/2 inhibitor) and partially reversed by RAGE knockdown. (3)RAGE knockdown partially reversed the promoted effect of cell proliferation, migration and invasion induced by HMGB1. Conclusion HMGB1 promotes the development and progression of CCRCC via ERK1/2 activation, which is partially mediated by RAGE.