The ETS gene ETV4 is required for anchorage-independent growth and a cell proliferation gene expression program in PC3 prostate cells

Peter C. Hollenhorst, Litty Paul, Mary W. Ferris, Barbara J. Graves

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Chromosomal abnormalities that give rise to elevated expression levels of the ETS genes ETV1, ETV4, ETV5, or ERG are prevalent in prostate cancer, but the function of these transcription factors in carcinogenesis is not clear. Previous work in cell lines implicates ERG, ETV1, and ETV5 as regulators of invasive growth but not transformation. Here, we show that the PC3 prostate cancer cell line provides a model system to study the overexpression of ETV4. Migration assays, anchorage-independent growth assays, and microarray analysis indicate that high ETV4 expression contributes to both transformation and cellular motility in PC3 cells. ETV4 directly bound the 5' and 3' MYC enhancers and modulated expression of both MYC and other cell proliferation genes, demonstrating a potential role in cell growth control. Despite this novel role for ETV4 in anchorage-independent growth, ETV4 overexpression in normal prostate-derived RWPE-1 cells showed effects similar to ETV1 overexpression: increased cellular motility and an upregulation of genes encoding extracellular proteins as well as ones important for development, inflammation, and wound healing. Because ETV1 and ETV4 have similar roles when introduced to the same cellular background, we suggest that the requirement of high ETV4 expression for maintenance of the anchorage-independent growth in PC3 cells is due to a specific characteristic of this cell line rather than a function of ETV4 that is distinct from the other oncogenic ETS genes. Thus, the function of ETS genes in prostate cancer may differ based on other genetic alterations in a tumor.

Original languageEnglish (US)
Pages (from-to)1044-1052
Number of pages9
JournalGenes and Cancer
Volume1
Issue number10
DOIs
StatePublished - Dec 1 2010

    Fingerprint

Keywords

  • ETS
  • ETV4
  • PC3
  • Prostate cancer
  • Transformation

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this