Tumor-specific Transcription Factor Binding to an Activator Protein-2/Sp1 Element of the Urokinase-type Plasminogen Activator Receptor Promoter in a First Large Series of Resected Gastrointestinal Cancers

摘要: Purpose: Evidence for transactivation of genes via specific promoter elements has been derived from studies on tumor cell lines but rarely resected tumors. However, the proof an in vivo relevance and identification patients with a potential tumor-specific gene expression is essential to transfer molecular-targeting strategies into clinical applications. This study gives first evidence that urokinase-type plasminogen activator receptor (u-PAR) tumor-specifically regulated protein (AP)-2/Sp1 element large patient subpopulation. Experimental Design: In 145 gastrointestinal cancer patients, electrophoretic mobility shift analysis supershift assays u-PAR-promoter region −152/−135 were performed tumors corresponding normal tissues. u-PAR levels measured by ELISA. Results: Binding Sp1 contrast mucosae was observed 55% colorectal 52% gastric patients. Tumor-specific binding AP-2-related factor seen 59% 63% A significant correlation between AP-2 ( P = 0.0003) high not mucosae. Tissues five nontumor did show transcription this region. Conclusions: trans -activators (−152/−135) biochemically series For subpopulation ∼60% tumor-restricted u-PAR-transactivation, molecular targeting or its activating pathways should be pursued as new antimetastasis therapy approach.