Gene Set: SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX5_DN

Standard name SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX5_DN
Systematic name M1363
Brief description Early prostate development genes (down-regulated at 12 hr dihydrotestosterone [PubChem=10635]) which are also down-regulated in high grade prostatic intraepithelial neoplasia (PIN) vs invasive cancer.
Full description or abstract 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18794802   Authors: Schaeffer EM,Marchionni L,Huang Z,Simons B,Blackman A,Yu W,Parmigiani G,Berman DM
Exact source Table 17S
Related gene sets (show 18 additional gene sets from the source publication)

(show 10 gene sets from the same authors)
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Organism Mus musculus
Contributed by Jessica Robertson (Broad Institute)
Source platform MOUSE_GENE_SYMBOL
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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