Activation of the WT1 tumor suppressor gene promoter by Pea3.
Gene array profiling of RNA from cells engineered to express a dominant-negative version of the ETS family member transcription factor Pea3 (polyomavirus enhancer activator 3) identified WT1 as a candidate downstream gene. Given the co-expression of WT1 and Pea3 in developing kidney and breast tissue undergoing mesenchymal to epithelial transitions, we further characterized this potential gene hierarchy. Analysis of the human WT1 promoter revealed several potential binding sites for Pea3. Pea3 transactivated the WT1 promoter in transient transfection assays and bound to specific sites within the WT1 promoter in vitro. Our results position Pea3 upstream of WT1 and define a gene hierarchy important for mesenchymal-epithelial transitions.
Discenza
Maria Teresa
MT
Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, QC, Canada H3G 1Y6.
Vaz
Darryl
D
Hassell
John A
JA
Pelletier
Jerry
J
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D001943:Breast Neoplasms; D016466:CHO Cells; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D015972:Gene Expression Regulation, Neoplastic; D016162:Genes, Wilms Tumor; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D025721:WT1 Proteins; D009396:Wilms Tumor / Q000235:genetics*
D014157:Transcription Factors; D025721:WT1 Proteins; C065788:transcription factor PEA3