Evolutionary conservation of transcription factor binding sites and gene regulation of prostate cancer genes

Helen Piontkivska
Department of Biological Sciences, Kent State University, Kent, OH 44242 opiontki@kent.edu

In the United States, prostate cancer (PC) is one of the most common forms of cancer, and unfortunately, also one of the most deadly.
Delineating signaling pathways and gene regulation in prostate cancer cells is critical for understanding processes involved in cancer
 progression. Gene expression studies have identified Wilms tumor gene
(WT1) as one of the important genes in PC, although its function remains unclear. Evolutionary analysis of promoter sequences of potential 
WT1-regulated candidate genes allowed us to identify target genes with functional binding sites of WT1 and other growth factors including
 EGR1 and GATA1. Of many promoter elements found to be conserved among different mammalian genomes, some were even shared among distantly 
related genomes such as human and opossum (separated by over 170 million years of evolution), suggesting functional importance of such
 regulatory pathways. Overall, using evolutionary conservation of promoter elements, novel regulatory targets of WT1 were discovered, 
providing valuable insights to aid discovery of novel regulatory networks in PC.