The wilms tumor suppressor WT1 enhances CD95L expression and promotes activation‐induced‐cell‐death in leukemic T cells

In this study, we investigated WT‐1 expression in ten T‐ALL cell lines established from leukemia/lymphoma patients. We show that consistent with the finding in primary T‐ALL cells, most of the leukemic T‐cell lines tested do not over‐express WT1 proteins. We found that leukemic T‐cells over‐expressing WT1 protein produce higher levels of CD95L and show elevated CD95L‐mediated activation‐induced cell death compared to cells lacking or expressing low levels of WT1. Ectopic expression of WT1 in the WT1‐non‐expressing leukemic T‐cell line increases CD95L expression and elevates activation‐induced apoptosis, whereas silencing WT1 expression in the WT1‐over‐expressing leukemic T‐cell line by siRNA confers reduced CD95L expression and reduction in activation‐induced cell death. ChIP and Luciferase‐promoter reporter analysis demonstrate that WT1 binds to and enhances CD95L promoter activity through the Egr‐binding sites. Our study provides a new role of WT1 in regulation of CD95L‐mediated cell death. © 2013 Wiley Periodicals, Inc.
Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Cancer Cell Biology Source Type: research