Receptor for advanced glycation end products (RAGE) partially mediates HMGB1-ERKs activation in clear cell renal cell carcinoma.
J Cancer Res Clin Oncol
; 138(1): 11-22, 2012 Jan.
Article
em En
| MEDLINE
| ID: mdl-21947243
ABSTRACT
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:
â 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. â¡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. â¢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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
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Receptores Imunológicos
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Proteína HMGB1
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MAP Quinases Reguladas por Sinal Extracelular
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Neoplasias Renais
Limite:
Humans
Idioma:
En
Revista:
J Cancer Res Clin Oncol
Ano de publicação:
2012
Tipo de documento:
Article