Nkx3.1 controls the DNA repair response in the mouse prostate

Prostate. 2016 Mar;76(4):402-8. doi: 10.1002/pros.23131. Epub 2015 Dec 10.

Abstract

Background: The human prostate tumor suppressor NKX3.1 mediates the DNA repair response and interacts with the androgen receptor to assure faithful completion of transcription thereby protecting against TMPRSS2-ERG gene fusion. To determine directly the effect of Nkx3.1 in vivo we studied the DNA repair response in prostates of mice with targeted deletion of Nkx3.1.

Methods: Using both drug-induced DNA damage and γ-irradiation, we assayed expression of γ-histone 2AX at time points up to 24 hr after induction of DNA damage.

Results: We demonstrated that expression of Nkx3.1 influenced both the timing and magnitude of the DNA damage response in the prostate.

Conclusions: Nkx3.1 affects the DNA damage response in the murine prostate and is haploinsufficient for this phenotype.

Keywords: DNA repair; NKX3.1; haploinsufficiency; γhistone 2AX.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • DNA / drug effects
  • DNA / radiation effects
  • DNA Damage
  • DNA Repair / physiology*
  • Etoposide / pharmacology
  • Gamma Rays
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Mitomycin / pharmacology
  • Prostate / metabolism*
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • Homeodomain Proteins
  • Nkx3-1 protein, mouse
  • Transcription Factors
  • Mitomycin
  • Etoposide
  • DNA