title: An Interaction with Ewing's Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate Cancer.
abstract: More than 50% of prostate tumors have a chromosomal rearrangement resulting in aberrant expression of an oncogenic ETS family transcription factor. However, mechanisms that differentiate the function of oncogenic ETS factors expressed in prostate tumors from non-oncogenic ETS factors expressed in normal prostate are unknown. Here, we find that four oncogenic ETS (ERG, ETV1, ETV4, and ETV5), and no other ETS, interact with the Ewing's sarcoma breakpoint protein, EWS. This EWS interaction was necessary and sufficient for oncogenic ETS functions including gene activation, cell migration, clonogenic survival, and transformation. Significantly, the EWS interacting region of ERG has no homology with that of ETV1, ETV4, and ETV5. Therefore, this finding may explain how divergent ETS factors have a common oncogenic function. Strikingly, EWS is fused to various ETS factors by the chromosome translocations that cause Ewing's sarcoma. Therefore, these findings link oncogenic ETS function in both prostate cancer and Ewing's sarcoma.
authors: Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN 47405, USA.
authors: Vivekananda
authors: V
authors: Kedage
authors: Medical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USA.
authors: Nagarathinam
authors: N
authors: Selvaraj
authors: Department of Biology, Indiana University, Bloomington, IN 47405, USA.
authors: Taylor R
authors: TR
authors: Nicholas
authors: Medical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USA.
authors: Justin A
authors: JA
authors: Budka
authors: Department of Biology, Indiana University, Bloomington, IN 47405, USA.
authors: Joshua P
authors: JP
authors: Plotnik
authors: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Travis J
authors: TJ
authors: Jerde
authors: Medical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USA. Electronic address: pchollen@indiana.edu.
authors: Peter C
authors: PC
authors: Hollenhorst
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D008297:Male; D008819:Mice, Nude; D009857:Oncogenes; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D034802:RNA-Binding Protein EWS / Q000378:metabolism*; D012512:Sarcoma, Ewing / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D050784:Proto-Oncogene Protein c-ets-1; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors
keywords: ERG; ETS; EWS; Ewing’s sarcoma; prostate cancer