Figure 1.

RB1 loss, but not TP53 loss, contributes to OC2 activation. A. OC2 activity in comparison to TP53 and RB1 expression in SU2C CRPC patient cohorts [3]. All samples were separated into high and low groups based on the transcriptional expression level. The RB1 copy number loss correlates with its expression level and serves as a potential biomarker for stratifying OC2-activated patients. B. LNCaP model with RB1 knockout or combined knockout of RB1/TP53 show increased OC2 expression. TP53 single knockout did not change OC2 expression level. C. Knockdown of RB1 with shRNA activates OC2 in an independent LNCaP model. D. In genetically engineered mouse models (GEMMs), Rb1 knockout and Rb1/Tp53 combined knockout in a Pten-null background elevate both expression and activity of OC2. E. Rb1-null/Pten-null GEMM shows epigenetic activation with loss of repressive mark (K27me3) and gain of activation mark (K4me3) at the Onecut2 promoter compared to Pten-null GEMM.