Tumor-specific transcription factor binding to an @entity18720 / @entity3419 element of the XXXX promoter in a first large series of resected @entity1820 .

@entity1 @entity10431 @entity5 @entity1820 @entity3419 @entity18720 @entity356
PURPOSE: Evidence for transactivation of genes via specific promoter elements has been derived from studies on @entity5 cell lines but rarely on resected @entity5 . However, the proof of an in vivo relevance and the identification of @entity1 with a potential @entity5 -specific gene expression is essential to transfer molecular-targeting strategies into clinical applications. This study gives the first clinical evidence that @entity10431 ( @entity10431 ) gene expression is @entity5 -specifically regulated via an activator protein (AP)-2/ @entity3419 promoter element in a large @entity1 subpopulation. EXPERIMENTAL DESIGN: In 145 @entity1820 @entity1 , electrophoretic mobility shift analysis and supershift assays for @entity10431 -promoter region -152/-135 were performed in @entity5 and corresponding normal tissues. @entity10431 protein levels were measured by ELISA. RESULTS: Binding of @entity3419 to region -152/-135 in @entity5 in contrast to corresponding normal mucosae was observed in 55% of colorectal and in 52% of @entity356 @entity1 . Tumor-specific binding of an @entity18720 -related factor was seen in 59% of colorectal and in 63% of @entity356 @entity1 . A significant correlation between @entity18720 (P < 0.0001) and @entity3419 (P = 0.0003) binding with a high @entity10431 expression was observed in @entity5 but not in normal mucosae. Tissues of five nontumor @entity1 did not show transcription factor binding to this region. CONCLUSIONS: This is the first study to show the @entity5 -specific binding of trans-activators to the @entity10431 promoter region (-152/-135) biochemically in a large series of resected @entity5 . For the subpopulation of approximately 60% of @entity1 with @entity5 -restricted @entity10431 -transactivation, a molecular targeting of this region or its activating pathways should be pursued as a new antimetastasis therapy approach.
