Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer.
BMC Cancer
; 11: 139, 2011 Apr 16.
Article
em En
| MEDLINE
| ID: mdl-21496277
ABSTRACT
BACKGROUND:
A cross-talk between different receptor tyrosine kinases (RTKs) plays an important role in the pathogenesis of human cancers.METHODS:
Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA) silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients.RESULTS:
A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α) with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α in vitro was through a ras- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (p < 0.05), and overexpression of c-Met/Axl/PDGFR-α or c-Met alone showed the most significant correlation with poor survival (p < 0.01).CONCLUSIONS:
In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy.
Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
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Proteína Oncogênica p21(ras)
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Ativação Transcricional
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Proteína Oncogênica pp60(v-src)
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Proteínas Proto-Oncogênicas
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Receptores Proteína Tirosina Quinases
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Proteínas Proto-Oncogênicas c-met
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Receptor alfa de Fator de Crescimento Derivado de Plaquetas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
BMC Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Taiwan