STANDARD_NAME SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX4_UP SYSTEMATIC_NAME M1358 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX4_UP NAMESPACE MOUSE_GENE_SYMBOL DESCRIPTION_BRIEF Early prostate development genes (up-regulated at 6 hr dihydrotestosterone [PubChem=10635]) which are also up-regulated in localized vs metastatic prostate cancers. DESCRIPTION_FULL Cancer cells differentiate along specific lineages that largely determine their clinical and biologic behavior. Distinct cancer phenotypes from different cells and organs likely result from unique gene expression repertoires established in the embryo and maintained after malignant transformation. We used comprehensive gene expression analysis to examine this concept in the prostate, an organ with a tractable developmental program and a high propensity for cancer. We focused on gene expression in the murine prostate rudiment at three time points during the first 48 h of exposure to androgen, which initiates proliferation and invasion of prostate epithelial buds into surrounding urogenital sinus mesenchyme. Here, we show that androgen exposure regulates genes previously implicated in prostate carcinogenesis comprising pathways for the phosphatase and tensin homolog (PTEN), fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK), and Wnt signaling along with cellular programs regulating such 'hallmarks' of cancer as angiogenesis, apoptosis, migration and proliferation. We found statistically significant evidence for novel androgen-induced gene regulation events that establish and/or maintain prostate cell fate. These include modulation of gene expression through microRNAs, expression of specific transcription factors, and regulation of their predicted targets. By querying public gene expression databases from other tissues, we found that rather than generally characterizing androgen exposure or epithelial budding, the early prostate development program more closely resembles the program for human prostate cancer. Most importantly, early androgen-regulated genes and functional themes associated with prostate development were highly enriched in contrasts between increasingly lethal forms of prostate cancer, confirming a 'reactivation' of embryonic pathways for proliferation and invasion in prostate cancer progression. Among the genes with the most significant links to the development and cancer, we highlight coordinate induction of the transcription factor Sox9 and suppression of the proapoptotic phospholipid-binding protein Annexin A1 that link early prostate development to early prostate carcinogenesis. These results credential early prostate development as a reliable and valid model system for the investigation of genes and pathways that drive prostate cancer. PMID 18794802 GEOID GSE12077 AUTHORS Schaeffer EM,Marchionni L,Huang Z,Simons B,Blackman A,Yu W,Parmigiani G,Berman DM CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 16S FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 2410127E18Rik,Fabp4,Irf2bp2,Krt19,Nav1,Ncoa6,Prkcb1,Prkcbp1,Sdpr,Sin3b,Wac GENE_SYMBOLS KLHDC10,FABP4,IRF2BP2,KRT19,NAV1,NCOA6,PRKCB,ZMYND8,CAVIN2,SIN3B,WAC FOUNDER_NAMES