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Androgen-Dependent Oncogenic Activation of ETS Transcription Factors by Recurrent Gene Fusions in Prostate Cancer: Biological and Clinical Implications

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Androgen-Responsive Genes in Prostate Cancer

Abstract

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.

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Authors and Affiliations

  1. Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Science, Bethesda, MD, 20814, USA

    Albert Dobi, Taduru Sreenath & Shiv Srivastava PhD

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  1. Albert Dobi
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  2. Taduru Sreenath
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  3. Shiv Srivastava PhD
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Correspondence to Shiv Srivastava PhD .

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  1. , Shadyside Medical Center, University of Pittsburgh, Centre Ave 5200, Pittsburgh, 15232, Pennsylvania, USA

    Zhou Wang

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Dobi, A., Sreenath, T., Srivastava, S. (2013). Androgen-Dependent Oncogenic Activation of ETS Transcription Factors by Recurrent Gene Fusions in Prostate Cancer: Biological and Clinical Implications. In: Wang, Z. (eds) Androgen-Responsive Genes in Prostate Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6182-1_19

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