CAJ | 학술논문

目的观察晚期糖基化终产物受体(RAGE)和高迁移率族蛋白B1-细胞外信号调节激酶(HMGB1-ERKs)在肾透明细胞癌(CCRCC)发生进展中的作用.方法采用组织芯片技术检测CCRCC中RAGE和HMGB1的表达.HMGB1对静态或RAGE低表达的CCRCC细胞进行干预,Western blot法检测ERKl/2磷酸化表达.结果 CCRCC中RAGE及HMGB1共表达水平升高与患者的临床参数包括肿瘤大小(≤7.0 cm,72.4％;＞7.0 cm,27.6％)、核Fuhrman分级(G1,8.2％;G2,43.5％;G3,38.3％;G4,10.0％)和临床分期(Ⅰ期,63.5％;Ⅱ期,13.3％;Ⅲ期,14.1％;Ⅳ期,9.1％)呈正相关(P＜0.05).在HMGB1潜伏期内ERKl/2活化具有时间和剂量依赖性,其激活可被U0126[丝裂原细胞外激酶(MEK1/2)抑制剂]完全阻断或被RAGE下调部分逆转.结论 HMGB1可通过RAGE部分调节而活化ERK1/2,从而促进CCRCC的发生和发展.
목적 관찰만기당기화종산물수체(RAGE)화고천이솔족단백B1-세포외신호조절격매(HMGB1-ERKs)재신투명세포암(CCRCC)발생진전중적작용.방법 채용조직심편기술검측CCRCC중RAGE화HMGB1적표체.HMGB1대정태혹RAGE저표체적CCRCC세포진행간예,Western blot법검측ERKl/2린산화표체.결과 CCRCC중RAGE급HMGB1공표체수평승고여환자적림상삼수포괄종류대소(≤7.0 cm,72.4％;＞7.0 cm,27.6％)、핵Fuhrman분급(G1,8.2％;G2,43.5％;G3,38.3％;G4,10.0％)화림상분기(Ⅰ기,63.5％;Ⅱ기,13.3％;Ⅲ기,14.1％;Ⅳ기,9.1％)정정상관(P＜0.05).재HMGB1잠복기내ERKl/2활화구유시간화제량의뢰성,기격활가피U0126[사렬원세포외격매(MEK1/2)억제제]완전조단혹피RAGE하조부분역전.결론 HMGB1가통과RAGE부분조절이활화ERK1/2,종이촉진CCRCC적발생화발전.
Objective To explore the expression of receptor for advanced glycation end products (RAGE) and high-mobility group box-1 (HMGB1) and their role in development and progression of clear cell renal cell carcinoma (CCRCC).Methods The expression of RAGE and HMGB1 was examined in CCRCC by using tissue microarrays.In vitro,quiescent or RAGE-reduced CCRCC cells were subjected to treatment with HMGB1 and harvested for detecting extracellular signal regulated kinase (ERK1/2) phosphorylation via Western blotting.Results Elevated co-expression of RAGE and HMGB1 in CCRCC was correlated positively with tumor size (≤7.0 cm,72.4％ ; ＞ 7.0 cm,27.6％),nuclear Fuhrman grade (G1,8.2％ ; G2,43.5％ ; G3,38.3％ ; G4,10.0％) and clinical stage (Ⅰ,63.5％ ; Ⅱ,13.3％ ;Ⅲ,14.1％; Ⅳ,9.1％) (P ＜ 0.05).HMGB1 incubation induced ERK1/2 activation in a time-and dose-dependent manner,which could be completely blocked by U0126 [mitogen extracellular kinase (MEK) 1/2 inhibitor] and partially reversed by RAGE knockdown.Conclusion HMGB1 promotes the devdopment and progression of CCRCC via ERK1/2 activation,which is partially mediated by RAGE.