NKX3.1 Suppresses TMPRSS2-ERG gene rearrangement and mediates repair of androgen receptor-induced DNA damage

Cai Bowen, Tian Zheng, Edward P. Gelmann

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

TMPRSS2 gene rearrangements occur at DNA breaks formed during androgen receptor-mediated transcription and activate expression of ETS transcription factors at the early stages of more than half of prostate cancers. NKX3.1, a prostate tumor suppressor that accelerates the DNA repair response, binds to androgen receptor at the ERG gene breakpoint and inhibits both the juxtaposition of the TMPRSS2 and ERG gene loci and also their recombination. NKX3.1 acts by accelerating DNA repair after androgen-induced transcriptional activation. NKX3.1 influences the recruitment of proteins that promote homology-directed DNA repair. Loss of NKX3.1 favors recruitment to the ERG gene breakpoint of proteins that promote error-prone nonhomologous end-joining. Analysis of prostate cancer tissues showed that the presence of a TMPRSS2-ERG rearrangement was highly correlated with lower levels of NKX3.1 expression consistent with the role of NKX3.1 as a suppressor of the pathogenic gene rearrangement.

Original languageEnglish (US)
Pages (from-to)2686-2698
Number of pages13
JournalCancer Research
Volume75
Issue number13
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'NKX3.1 Suppresses TMPRSS2-ERG gene rearrangement and mediates repair of androgen receptor-induced DNA damage'. Together they form a unique fingerprint.

Cite this