Translocation of ETS transcription factors ERG (avian erythroblastosis virus E-26 (v-ets) oncogene related), ETV1, ETV4, EV5, and FLI1 occur in half of all prostate cancers. TMPRSS2 (transmembrane protease, serine 2)-ERG translocation is the most common molecular alteration.
These Rosa26ERG mice conditionally express the TMPRSS2-ERG fusion transcription factor as well as a nuclear-localized EGFP from the Gt(ROSA26)Sor gene after cre-mediated excision of a loxP-flanked Stop sequence. When crossed into probasin (Pbsn)-cre, ERG is specifically and strongly expressed in the prostate, causing a low penetrance of prostate hyperplasia. When bred with Pbsn-cre and Pten floxed mice (to knock out PTEN expression in the prostate), ERG expression causes accelerated, highly penetrant invasive prostate cancer in the progeny. Triple mutant mice show invasive adenocarcinoma characterized by small irregular glandular structures composed of malignant cells with large, pleiomorphic nuclei and pale cytoplasm developed adjacent to prostatic intraepithelial neoplasia by 8 weeks of age. By 6 months, approximately 80% of these mice contain regions of adenocarcinoma with enlarged, hardened prostates.
EGFP expression can be detected directly or through immunohistochemistry.
