NKX3.1 Suppresses TMPRSS2-ERG Gene Rearrangement and Mediates Repair of Androgen Receptor-Induced DNA Damage.

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.

Bowen C ，Zheng T ，Gelmann EP 《-》

Genetic interaction between Tmprss2-ERG gene fusion and Nkx3.1-loss does not enhance prostate tumorigenesis in mouse models.

Linn DE ，Bronson RT ，Li Z 《PLoS One》

Loss of the NKX3.1 tumorsuppressor promotes the TMPRSS2-ERG fusion gene expression in prostate cancer.

Thangapazham R ，Saenz F ，Katta S ，Mohamed AA ，Tan SH ，Petrovics G ，Srivastava S ，Dobi A ... -  《BMC CANCER》

TMPRSS2:ERG fusion by translocation or interstitial deletion is highly relevant in androgen-dependent prostate cancer, but is bypassed in late-stage androgen receptor-negative prostate cancer.

Hermans KG ，van Marion R ，van Dekken H ，Jenster G ，van Weerden WM ，Trapman J ... -  《CANCER RESEARCH》

ERG gene rearrangements are common in prostatic small cell carcinomas.

Lotan TL ，Gupta NS ，Wang W ，Toubaji A ，Haffner MC ，Chaux A ，Hicks JL ，Meeker AK ，Bieberich CJ ，De Marzo AM ，Epstein JI ，Netto GJ ... -  《-》