Abstract
This paper used the Sleeping Beauty transposon insertional mutagenesis system to identify genes that accelerate the development of KrasG12D-induced pancreatic ductal adenocarcinoma (PDA) in mice. In more than 50% of the tumours the Usp9x gene, which encodes a deubiquitylase, was inactivated. Analyses of human PDA samples indicated that low USP9X mRNA and protein levels correlate with a poor prognosis. Interestingly, treatment of human PDA cell lines with chromatin-modifying drugs, such as 5-aza-2′-deoxycytidine, increased USP9X expression, suggesting that epigenetic therapies might be appropriate for some patients with PDA.
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