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Wilms Tumor Nikki Etxegoien Wilm’s Tumor The Wilms’ Tumor 1 (WT1) Protein WT1 Acts on Many Protein Targets Proteins important in the cell to cell interactions necessary for cell differentiation Transcription Factors Growth Factors and Growth Factor Receptors Also acts on proteins important in cell mediated apoptosis like Bcl-2 Wt 1 Behaves like Rb © 2008 Holloway et al; licensee BioMed Central Ltd Knudson’s Two Hit Hypothesis When the mutation is inherited (in a dominant fashion) a second somatic mutation causes bilateral tumor development WT1 plays an important role in Human Kidney development WT1 is needed for this the metanephric mesenchyme epithelial transition Coordinating Early Kidney Development: Lessons from gene Targeting Nature Reviews Genetics 3, 533-543 (July 2002) How Was the Role of WT1 Discovered? By knocking out the gene in vivo! This phenotype is lethal at Embryonic day 12 Many mutations can cause the mutant WT1 phenotype Mutations in WT1 have been linked to other disorders and cancers
