Functional Roles of Wilms’ Tumor 1 (WT1) in Malignant Brain Tumors

ABSTRACT

The pleiotropic transcription factor, Wilms’ tumor 1 (WT1), is expressed in the majority of glioblastomas, the most common malignant brain tumors of adulthood. Despite intensive treatment, including surgery and chemoradiotherapy, the prognosis for patients with glioblastoma remains very poor. Encouragingly, immunotherapy targeting WT1 has proven to be effective in recurrent glioblastoma, suggesting that this approach may be an important new treatment modality for the disease. However, WT1 appears to function as a context-dependent tumor suppressor or oncogene, and the functional roles of WT1 in the pathogenesis of glioblastoma, and other types of brain tumors, have not been extensively studied. With this in mind, we briefly review WT1 expression data for a range of different brain tumor classes and address the role of WT1 in the regulation of proliferation and apoptosis in glioblastoma. We generated WT1 knockdown glioblastoma cells by using shRNA-expressing lentivirus. Proliferation was reduced and apoptosis increased in WT1 knockdown glioblastoma cells compared with control cells in vitro. Consistent with these data, when WT1 knockdown glioblastoma cells or control glioblastoma cells were intracranially injected into the immunodeficient mice, tumor growth was significantly reduced in WT1 knockdown cells compared with that in control cells. Thus, WT1 is an oncogene that regulates cell proliferation and apoptosis in glioblastoma.