Suppression of CHK1 by ETS Family Members Promotes DNA Damage Response Bypass and Tumorigenesis.

ABSTRACT:

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The ETS family of transcription factors has been repeatedly implicated in tumorigenesis. In prostate cancer, ETS family members, such as ERG, ETV1, ETV4, and ETV5, are frequently overexpressed due to chromosomal translocations, but the molecular mechanisms by which they promote prostate tumorigenesis remain largely undefined. Here, we show that ETS family members, such as ERG and ETV1, directly repress the expression of the checkpoint kinase 1 (CHK1), a key DNA damage response cell-cycle regulator essential for the maintenance of genome integrity. Critically, we find that ERG expression correlates with CHK1 downregulation in human patients and demonstrate that Chk1 heterozygosity promotes the progression of high-grade prostatic intraepithelial neoplasia into prostatic in

SUBMITTER: Lunardi A 

PROVIDER: S-EPMC6010310 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature