Figure 1: Biology of TMPRSS2-ERG gene fusions in prostate cancer. Association of bound androgen receptor with TMPRSS2 in fusion genes results in the upregulation of ERG transcription (or other Ets gene family members, i.e. ETV1, ETV4, and ETV5). This over production of ERG can then exert its effects by binding target gene promoter regions, which results in their activation or inhibition, and the generation of a neoplastic phenotype. Known direct target genes of ERG in TMPRSS2-ERG fusion positive tissues include MMP3, PLAU, LAMC2, KCNS3, PLA1A, C-MYC, GNMT, SARDH, CXCR4, ADAMTS1,TFF3, ERG, PLAT, MMP9, NDRG1, CUTL2, AR, KLK3 (PSA), KLK2, SLC43A1, FKBP5, EZH2, ZBTB16, HPGD, ZEB1, SPINT1, IL1R2, PSMA, and OPN. These and other up or down regulated genes in fusion positive cancers could facilitate PC progression. In addition, both PTEN loss and AKT overexpression facilitate the development of invasive carcinoma in TMPRSS2-ERG positive prostate tissues.