WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis.

摘要: Abstract The Wilms tumor suppressor gene WT1 encodes a developmentally regulated transcription factor that is mutated in subset of embryonal tumors. To test its functional properties, we developed osteosarcoma cell lines expressing under an inducible tetracycline-regulated promoter. Induction resulted programmed death. This effect, which was differentially mediated by the alternative splicing variants WT1, independent p53. WT1-mediated apoptosis associated with reduced synthesis epidermal growth receptor (EGFR), but not other postulated WT1-target genes, and it abrogated constitutive expression EGFR. repressed from EGFR promoter, binding to two TC-rich repeat sequences. In developing kidney, renal precursor cells declined onset expression. Repression induction mechanism may contribute critical role normal kidney development immortalization inactivated alleles.