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Protocols for Studies on TMPRSS2/ERG in Prostate Cancer

  • Hubert Pakula
  • Douglas E. Linn
  • Daniel R. Schmidt
  • Marit Van Gorsel
  • Matthew G. Vander Heiden
  • Zhe LiEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1786)

Abstract

TMPRSS2/ERG is the most common type of gene fusions found in human prostate cancer. There are two important features of TMPRSS2/ERG fusions. One is that these gene fusions lead to ectopic expression of ERG, an ETS family transcription factor, in prostate epithelial cells from the 5′ control region of an androgen/estrogen dual-responsive gene, TMPRSS2; the other is that ~60% of these fusions are generated via intrachromosomal deletion of the interstitial region between TMPRSS2 and ERG. To recapitulate these important aspects of TMPRSS2/ERG fusions, we generated several TMPRSS2/ERG knockin mouse models based on the endogenous Tmprss2 locus. We found that TMPRSS2/ERG represents an early event in prostate tumorigenesis, by sensitizing prostate cells for cooperation with other oncogenic events, such as PTEN-deficiency. We also found that the interstitial region between TMPRSS2 and ERG harbors at least one prostate tumor suppressor, ETS2, whose loss contributes to prostate cancer progression. In this protocol, we describe how these knockin mouse models can be utilized to study roles of TMPRSS2/ERG fusions in prostate cancer development both in vivo and in vitro.

Key words

TMPRSS2 ERG Gene fusion Mouse model Pb-Cre PTEN Interstitial deletion FACS Prostate regeneration Organoid culture 

Notes

Acknowledgments

This work was supported by a Career Development Award from Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (P50 CA090381) and by Idea Development Awards from Department of Defense (W81XWH-11-1-0329, W81XWH-15-1-0546) to Z.L.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Hubert Pakula
    • 1
  • Douglas E. Linn
    • 1
  • Daniel R. Schmidt
    • 2
  • Marit Van Gorsel
    • 3
  • Matthew G. Vander Heiden
    • 3
  • Zhe Li
    • 1
    Email author
  1. 1.Division of Genetics, Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  2. 2.Harvard Radiation Oncology ProgramBostonUSA
  3. 3.Department of Biology, The Koch Institute for Integrative Cancer ResearchMassachusetts Institute of TechnologyCambridgeUSA

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