title: Receptor for advanced glycation end products (RAGE) partially mediates HMGB1-ERKs activation in clear cell renal cell carcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  HMGB1 promotes the development and progression of CCRCC via ERK1/2 activation, which is partially mediated by RAGE.
authors.affiliation: 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. linliguo03127@126.com
authors.forename: Liguo
authors.initials: L
authors.lastname: Lin
authors.forename: Kaihua
authors.initials: K
authors.lastname: Zhong
authors.forename: Zhongkai
authors.initials: Z
authors.lastname: Sun
authors.forename: Guozhong
authors.initials: G
authors.lastname: Wu
authors.forename: Guodong
authors.initials: G
authors.lastname: Ding
mesh_terms: D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D024243:HMGB1 Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics
chemical_list: D024243:HMGB1 Protein; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D048049:Extracellular Signal-Regulated MAP Kinases