%0 Journal Article
%T Transcriptional activation of the Axl and PDGFR-¦Á by c-Met through a ras- and Src-independent mechanism in human bladder cancer
%A Chen-Yun Yeh
%A Shin-Mei Shin
%A Hsuan-Heng Yeh
%A Tsung-Jung Wu
%A Jyh-Wei Shin
%A Tsuey-Yu Chang
%A Giri Raghavaraju
%A Chung-Ta Lee
%A Jung-Hsien Chiang
%A Vincent S Tseng
%A Yuan-Chii G Lee
%A Cheng-Huang Shen
%A Nan-Haw Chow
%A Hsiao-Sheng Liu
%J BMC Cancer
%D 2011
%I BioMed Central
%R 10.1186/1471-2407-11-139
%X 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.A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-¦Á) 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-¦Á 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-¦Á or c-Met alone showed the most significant correlation with poor survival (p < 0.01).In addition to c-Met, the cross-talk with Axl and/or PDGFR-¦Á also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-¦Á expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy.The RTK c-Met is expressed during normal development and plays a crucial role in many cell regulatory processes [1]. After binding to its cognate ligand-hepatocyte growth factor (HGF), activated c-Met transmits signals implicated in the cell proliferation, motility, survival, and morphogenesis [2-4]. C-Met is over-expressed and usually associated with metastatic progression of a variety of human malignant tumors, including bladder cancer [1,5]. We have reported that c-Met is over-expressed in 32.3%, 63.2%, and 65.2% of superfici
%K Axl
%K PDGFR-¦Á
%K c-Met
%K bladder cancer
%U http://www.biomedcentral.com/1471-2407/11/139