Supplementary Figures S1-S7 from NKX3.1 Suppresses TMPRSS2–ERG Gene Rearrangement and Mediates Repair of Androgen Receptor–Induced DNA Damage

Bowen, Cai; Zheng, Tian; Gelmann, Edward P.

doi:10.1158/0008-5472.22405082.v1

00085472can143387-sup-141167_1_supp_0_nnw83c.pdf (138.53 kB)

Supplementary Figures S1-S7 from NKX3.1 Suppresses TMPRSS2–ERG Gene Rearrangement and Mediates Repair of Androgen Receptor–Induced DNA Damage

journal contribution

posted on 2023-03-30, 23:03 authored by Cai Bowen, Tian Zheng, Edward P. Gelmann

Supplementary Figures S1-S7. AR induces chromosome conformational change juxtaposing TMPRSS2 and ERG (S1); TMPRSS2-ERG rearrangement in different NKX3.1-expressing cell lines (S2); NKX3.1 has no effects on TMPRSS2-ERG gene rearrangement in the absence of AR (S3); NKX3.1 expression and TMPRSS2-ERG rearrangement are related to histologic grade (S4); AR and NKX3.1 are recruited to break sites on TMPRSS2 and ERG genes (S5); NKX3.1 facilitates assembly of OGG1 at ERG gene break site (S6); Transcription is not required for TMPRSS2-ERG juxtaposition or rearrangement (S7).

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ARTICLE 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. Cancer Res; 75(13); 2686–98. ©2015 AACR.