Figure 5 from MYBL2 Drives Prostate Cancer Plasticity: Inhibiting Its Transcriptional Target CDK2 for RB1-Deficient Neuroendocrine Prostate Cancer

Mybl2 is a genetic dependency associated with CDK2 expression in NEPC. A, Tumoral growth curve of murine DKO Ctl and DKO Mybl2 KO cells and (B) PPKO Ctl cells and PPKO Mybl2 KO cells in NOD SCID mice. Tumor growth was monitored by serial caliper measurements every second day for 16 days (D16). Tumor weight was measured at D16 after dissection (n = 5 mice per treatment group (±1 SEM). C, Top responses from the cancer therapeutics response portal analysis using a MYBL2 gene signature. DEMETER gene dependency of CDK family members 2, 5, and 7 across human prostate cancer cell lines indicating as significant, as outlined in Fig. 3A. D, Box plot graphs summarizing the RNA-seq analysis from published prostate cancer GEMMs (first and second graphs, including wild-type, SKO, DKO, NP:Nkx3.1CreERT2:Ptenf/f and NPp53:Nkx3.1CreERT2:Ptenf/f:Trp53f/f), and human samples (third graph, including CRPC and NEPC samples) indicate CDK2 upregulation in NEPC mouse models and human patients. E, Immunofluorescent IHC staining for CDK2 in DKO and (F) PPKO murine tumors indicates a significant loss of CDK2 expression following MYBL2 KO.