TMPRSS2-ERG promotes the initiation of prostate cancer by suppressing oncogene-induced senescence.

ABSTRACT: ERG translocations are commonly involved in the initiation of prostate neoplasia, yet previous experimental approaches have not addressed mechanisms of oncogenic inception. Here, in a genetically engineered mouse model, combining TMPRSS2-driven ERG with Kras^G12D led to invasive prostate adenocarcinomas, while ERG or Kras^G12D alone were non-oncogenic. In primary prostate luminal epithelial cells, following inducible oncogenic Kras expression or Pten depletion, TMPRSS2-ERG suppressed oncogene-induced senescence, independent of TP53 induction and RB1 inhibition. Oncogenic KRAS and TMPRSS2-ERG synergized to promote tumorigenesis and metastasis of primary luminal cells. The presence of TMPRSS2-ERG compared to a wild-type background was associated with a stemness phenotype

SUBMITTER: Fang L 

PROVIDER: S-EPMC9537368 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature