Androgen-dependent oncogenic activation of ETS transcription factors by recurrent gene fusions in prostate cancer: Biological and clinical implications

Albert Dobi, Taduru Sreenath, Shiv Srivastava*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

7 Scopus citations


Half of all prostate cancers in the Western countries harbor gene fusions that involve regulatory sequences of the androgen receptor (AR)-responsive genes (predominantlyTMPRSS2) and protein coding sequences of nuclear transcription factors of the ETS gene family (predominantlyERG). This leads to unscheduled androgen-dependent expression of ETS-related transcription factors in tumor cell-specific manner. Extensive evaluations ofERGalterations at genome, transcript, and protein levels demonstrate unprecedented specificity of ERG for detecting prostate tumor cells. Assessment ofERGalterations in combination with other common prostate cancer gene alterations (AMACR,PCA3,p63) has potential in improving CaP diagnosis. Utility of ERG in assessing the clinical behavior of prostate cancer is uncertain. Strong correlation ofERGexpression with known androgen-responsive genes in prostate tumors has potential in developing gene panels inclusive of ERG for monitoring androgen receptor functional status in the disease continuum. Studies focusing on oncogenic functions ofERGpoint to its involvement in: abrogating differentiation; facilitating cell invasion and epithelial to mesenchymal transition; and disrupting epigenetic, inflammatory, and DNA damage control mechanisms. Therapeutic targeting ofERGor ERG interacting proteins, such as PARP hold promise in developing new strategies for the treatment of prostate cancer. In summary multipronged evaluations of theERGin CaP continue to reflect the critical role of this prevalent oncogenic activation in a CaP.

Original languageEnglish
Title of host publicationAndrogen-Responsive Genes in Prostate Cancer
Subtitle of host publicationRegulation, Function and Clinical Applications
PublisherSpringer New York
Number of pages22
ISBN (Electronic)9781461461821
ISBN (Print)1461461812, 9781461461814
StatePublished - 1 Oct 2012
Externally publishedYes


  • Androgen receptor
  • ERG oncogene
  • ERG oncoprotein
  • ETS transcription factors
  • Gene fusion
  • Hormonal regulation
  • Prostate cancer


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