Control of gene expression in prostate epithelial cell differentiation hierarchy

摘要: The aim of present investigation is to elucidate the complex stem cell (SC) dynamics within prostate cancer, which can be exploited design novel diagnostic and therapeutic strategies for management cancer. In order determine precise transcriptional microRNA regulatory mechanisms modulating SC self-renewal differentiation, unique cellular assays have been developed in our lab. These utilise homogeneous sub-populations enriched from patient-derived cultures. Occasionally, line models mouse cancer xenografts were also employed. Using a prospective bioinformatic analysis gene expression data Birnie et. al., 2008, we identified LCN2, CEACAM6, S100p as candidate genes regulation differentiation. are over-expressed differentiated cells, compared SC, more similar pattern with each other than any gene. Since their promoters binding sites 32 common transcription factors, may therefore form co-regulated network and/or functions. Retinoic acid treatment induce all these genes, suggesting that play an important role retinoic acid-mediated epithelial could so-regulated by miR-128, miR-188, miR-548c, based on miRNA microarray generated this work. Patient-derived PrEC, BPH, PCa, CRPC profiled 766 miRNAs. This very specific signature, showed distinguish between PCa CRPC. integration pathways regulating both cycle (SC quiescence) cell-cell interaction (SC-stromal niche interaction) significantly influenced miRNAs during A lack telomerase expression/activity SCs, contrast progeny points towards quiescent nature cells. studies further revealed BPH disease sustained progenitor proliferation inhibition derived SCs suppress self-renewal; while not affected inhibition. We anticipate results, functional studies, will comprehensively establish detailed knowledge base active invaluable formulating efficient