晚期糖基化终产物受体（RAGE）部分介导 HMGB1-ERK 在肾透明细胞癌中的激活。
Receptor for advanced glycation end products (RAGE) partially mediates HMGB1-ERKs activation in clear cell renal cell carcinoma.
机构信息
Department of Urinary Surgery, MeiZhou People's Hospital, Meizhou Affiliated Hospital of Sun Yat-sen University, Huangtang Road, Meijiang District, Meizhou, Guangdong Province, 514031, People's Republic of China.
出版信息
J Cancer Res Clin Oncol. 2012 Jan;138(1):11-22. doi: 10.1007/s00432-011-1067-0. Epub 2011 Sep 24.
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
①Elevated co-expression of RAGE and HMGB1 in CCRCC was correlated positively with patients' clinical parameters including tumor size, nuclear Fuhrman grade and clinical stage. ②HMGB1 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. ③RAGE 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.
目的
探讨晚期糖基化终产物受体（RAGE）和高迁移率族蛋白 B1（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
使用组织微阵列检测 RCC 中 RAGE 和 HMGB1 的表达。在体外，使静止或 RAGE 减少的 RCC 细胞接受 HMGB1 处理，并通过 Western blot 检测 ERK1/2 磷酸化。进一步通过 Ki-67 免疫染色、划痕愈合和基质胶侵袭测定分别评估细胞增殖、迁移和侵袭。
结果
①CCRCC 中 RAGE 和 HMGB1 的高共表达与患者的临床参数（包括肿瘤大小、核 Fuhrman 分级和临床分期）呈正相关。②HMGB1 孵育以时间和剂量依赖的方式诱导 ERK1/2 激活，该激活可被 U0126（MEK1/2 抑制剂）完全阻断，并可部分被 RAGE 敲低逆转。③RAGE 敲低部分逆转了 HMGB1 诱导的细胞增殖、迁移和侵袭的促进作用。
结论
HMGB1 通过 ERK1/2 激活促进 CCRCC 的发生发展，其部分由 RAGE 介导。
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