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The Wilms' tumor suppressor WT1 enhances CD95L expression and promotes activation‐induced cell death in leukemic T cells
Author(s) -
Bourkoula Konstantina,
Englert Christoph,
Giaisi Marco,
Köhler Rebecca,
Krammer Peter H.,
LiWeber Min
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28379
Subject(s) - cell culture , ectopic expression , cancer research , jurkat cells , biology , programmed cell death , apoptosis , chromatin immunoprecipitation , leukemia , microbiology and biotechnology , gene silencing , wilms' tumor , t cell , promoter , gene expression , immunology , gene , immune system , biochemistry , genetics
The role of Wilms' tumor suppressor 1 (WT1) in leukemogenesis has been investigated mostly in acute (AML) and chronic (CML) myeloid leukemias. So far, its oncogenic role has been controversially discussed because both overexpression and inactivating mutations are found. A recent study on primary samples from patients with acute T‐cell leukemia (T‐ALL) revealed that most of them do not express WT1 proteins although they express WT1 mRNA. In our 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 overexpress WT1 proteins. We found that leukemic T‐cells overexpressing WT1 protein produce higher levels of CD95L and show elevated CD95L‐mediated activation‐induced cell death (AICD) compared to cells lacking or expressing low levels of WT1. Ectopic expression of WT1 in the WT1‐nonexpressing leukemic T‐cell line increases CD95L expression and elevates activation‐induced apoptosis, whereas silencing WT1 expression in the WT1‐overexpressing leukemic T‐cell line by siRNA confers reduced CD95L expression and reduction in AICD. Chromatin immunoprecipitation 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.