Abstract PR1: Oncogenic ETS over-expression mimics RAS/MAPK signaling in prostate cells

Abstract

Abstract The aberrant expression of an oncogenic ETS transcription factor is implicated in the progression of the majority of prostate cancers. The prostate cancer chromosomal rearrangements that drive over-expression are associated with one of four ETS genes, ERG, ETV1, ETV4 and ETV5. It is not clear how these four oncogenic ETS genes differ from the numerous other ETS genes expressed in normal prostate. We report that these oncogenic ETS proteins, but not other ETS factors, enhance prostate cell migration. Genome-wide binding analysis matched this specific biological function to occupancy of a unique set of genomic sites highlighted by the presence of ETS and AP-1 binding sequences. ETS/AP-1 binding sequences are prototypical RAS-responsive elements, but oncogenic ETS proteins activated a RAS/MAPK transcriptional program in the absence of MAPK activation. Thus, overexpression of oncogenic ETS proteins can replace RAS/MAPK pathway activation in prostate cells. The genomic description of this ETS/AP-1 regulated, RAS-responsive, gene expression program provides a resource for understanding the role of ETS factors in both prostate cancer and other cancers with either ETS or RAS pathway mutations. This abstract is also presented as Poster B26. Citation Format: Peter C. Hollenhorst, Mary W. Ferris, Megan A. Hull, Heejoon Chae, Sun Kim, Barbara J. Graves. Oncogenic ETS overexpression mimics RAS/MAPK signaling in prostate cells [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr PR1.