Abstract 3914: Wilms Tumor-1 (WT-1) and its target genes in gliomagenesis

WT-1 - a zinc-finger transcription factor - plays an important role during development, and is associated with the development of tumors of varied origins. Our laboratory has previously demonstrated the expression and importance of WT-1 in the growth of glial neoplasms. In this study, we have sought to identify its downstream targets in the specific context of gliomas. Methods & results: Using Real Time RT-PCR and Western Blotting, we demonstrate an inverse correlation between WT-1 and one of its established targets- IGF-1R. Also, using the gene expression profiling technique, we have identified some of its other target genes in U251-MG cells. Key genes that are down-regulated with WT-1 silencing include: PDGF-D, TYMS, INPP5A, EPAS-1 and CD97, while genes that are found to be up-regulated with WT-1 silencing include: TIMP-3 and LZTS-1. These results have been validated at the RNA and/ or protein level using Real Time RT-PCR and/ or Western Blot analysis. Further, we demonstrate the effects of manipulating WT-1 levels on some of these newly identified targets, selected for their importance in different aspects of tumor biology. Conclusion: WT-1 is clearly implicated in the development and progression of gliomas. By identifying the molecular allies that help this protein promote oncogenesis, we hope to gain important insights for the development of a multi-molecular targeting strategy against these aggressive tumors Abbreviations: IGF-1R: Insulin-like growth factor-1 Receptor; PDGF-D: Platelet-Derived Growth Factor-D; TYMS: Thymidylate Synthetase; INPP5A- Inositol Polyphosphate-5-Phosphatase; EPAS-1: endothelial PAS domain protein 1; TIMP-3: Tissue inhibitor metallopeptidase-3; LZTS-1: leucine zipper, putative tumor suppressor 1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3914.