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Transcript
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