Oncogenic ETS proteins mimic activated RAS/MAPK signaling in prostate cells

Peter Hollenhorst, Mary W. Ferris, Megan A. Hull, Heejoon Chae, Sun Kim, Barbara J. Graves

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

The aberrant expression of an oncogenic ETS transcription factor is implicated in the progression of the majority of prostate cancers, 40% of melanomas, and most cases of gastrointestinal stromal tumor and Ewing's sarcoma. Chromosomal rearrangements in prostate cancer result in overexpression of any one of four ETS transcription factors. How these four oncogenic ETS genes differ from the numerous other ETS genes expressed in normal prostate and contribute to tumor progression is not understood. 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 these ETS factors in both an oncogenic setting and the developmental processes where these genes normally function.

Original languageEnglish
Pages (from-to)2147-2157
Number of pages11
JournalGenes and Development
Volume25
Issue number20
DOIs
StatePublished - Oct 15 2011

Fingerprint

Transcription Factor AP-1
Prostate
Gastrointestinal Stromal Tumors
Prostatic Neoplasms
Transcription Factors
Developmental Genes
Proteins
Ewing's Sarcoma
Genes
Cell Movement
Melanoma
Genome
Gene Expression
Neoplasms

Keywords

  • Cell migration
  • ChiP-seq
  • ETS
  • Prostate cancer
  • RAS/MAPK

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Oncogenic ETS proteins mimic activated RAS/MAPK signaling in prostate cells. / Hollenhorst, Peter; Ferris, Mary W.; Hull, Megan A.; Chae, Heejoon; Kim, Sun; Graves, Barbara J.

In: Genes and Development, Vol. 25, No. 20, 15.10.2011, p. 2147-2157.

Research output: Contribution to journalArticle

Hollenhorst, Peter ; Ferris, Mary W. ; Hull, Megan A. ; Chae, Heejoon ; Kim, Sun ; Graves, Barbara J. / Oncogenic ETS proteins mimic activated RAS/MAPK signaling in prostate cells. In: Genes and Development. 2011 ; Vol. 25, No. 20. pp. 2147-2157.
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