Expression and effects of inhibition of type I insulin-like growth factor receptor XXXX kinase in @entity1073 .

@entity1 @entity69938 @entity522 @entity5 @entity4674 @entity8189 @entity442 @entity8186 @entity8187 @entity4910 @entity1892 @entity1073 @entity9190 @entity2856 @entity669
BACKGROUND: Type I insulin-like growth factor receptor ( @entity2856 ) @entity669 kinase induces significant oncogenic effects. Strategies to block @entity2856 signaling are being tested in clinical trials that include @entity1 with aggressive solid @entity5 . @entity1073 is a @entity1892 with poor prognosis and a tendency to develop resistance. The expression and potential significance of @entity2856 in @entity1073 are not known. DESIGN AND METHODS: We used reverse transcriptase polymerase chain reaction, quantitative real-time polymerase chain reaction, immunoprecipitation, western blotting, flow cytometry, and immunohistochemistry to analyze the expression of @entity2856 mRNA, and @entity2856 and pIGF-IR proteins in @entity1073 cell lines and @entity1 ' specimens. Selective and specific blockade of @entity2856 was achieved using @entity69938 and short-interfering RNA, respectively. Cell viability, apoptosis, cell cycle, cellular morphology, cell proliferation, and target proteins were then analyzed. RESULTS: We detected the expression of @entity2856 and pIGF-IR in @entity1073 cell lines. Notably, @entity2856 molecules/cell were markedly increased in @entity1073 cell lines compared with @entity1 B-lymphocytes. @entity2856 and pIGF-IR were also detected in 78% and 74%, respectively, of 23 primary @entity1073 specimens. Treatment of serum-deprived @entity1073 cell lines with @entity442 salvaged these cells from apoptosis. Selective inhibition of @entity2856 by @entity69938 decreased the viability and proliferation of @entity1073 cell lines, and induced apoptosis and cell cycle arrest. Selective inhibition of @entity2856 was associated with @entity522 , @entity8186 , @entity8187 , and @entity9190 cleavage, @entity4674 release, up-regulation of @entity8189 , and down-regulation of @entity4910 , pCdc2, pIRS-1, pAkt, and pJnk. Similar results were obtained by using @entity2856 short-interfering RNA. In addition, @entity69938 decreased the viability and proliferation of primary @entity1073 cells that expressed @entity2856 . CONCLUSIONS: @entity2856 is up-regulated and frequently activated in @entity1073 . Our data suggest that @entity2856 could be a molecular target for the treatment of @entity1073 .
