MP64-15 PRO-INFLAMMATORY CYTOKINE GENES ARE DRIVERS OF PROSTATE CANCER PROGRESSION AND CASTRATE RESISTANT PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II1 Apr 2018MP64-15 PRO-INFLAMMATORY CYTOKINE GENES ARE DRIVERS OF PROSTATE CANCER PROGRESSION AND CASTRATE RESISTANT PROSTATE CANCER Isaac Powell, Aliccia Bollig-Fischer, and Elisabeth Heath Isaac PowellIsaac Powell More articles by this author , Aliccia Bollig-FischerAliccia Bollig-Fischer More articles by this author , and Elisabeth HeathElisabeth Heath More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2060AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Introduction: We reported functional driver genes and network interaction of race specific and differentially expressed genes by use of bioinformatics and ingenuity pathway analysis among a large population of African American men (AAM) and European American men (EAM) (Powell, I et al 2013, Cancer Epid Bio Prev.). When unraveling the network we identified multiple biological signaling pathways, parts of which reported elsewhere, but when put together, they activate directly or indirectly the androgen receptor and other pathways associated with invasiveness and metastasis. The drivers of these pathways are pro-inflammatory cytokines. We will present these signaling pathways from our interactive network. METHODS Method: In our initial microarray analysis from formalin fixed radical prostatectomy specimens, we examined 227 genes from 517 genes associated with PCa showing significantly greater expression in PCa from AAM and EAM, and a subset of these genes were identified by bioinformatics and the network from Ingenuity Pathway analysis to be functionally interrelated and driver genes. RESULTS Results: Pro-Inflammatory cytokines TNF (tumor necrosis factor) IL1B, IL6 and IL8 from our gene profile activated several intermediaries that interact and activate transcription factors in the nucleus, NFkB and TGFB included in our network . These factors bind to the promoter region of the androgen receptor and promote PCa cell proliferation (Zhang 2009,Cao 2015). Inflammatory cytokines TNF and IL1B up-regulate MMP9 (Matrix metalloproteinase 9) in the microenvironment which down regulates cell adhesion molecule E-Cadherin and allows tumors cells to become invasive (Zhang 1998, Canbay, 2015 ) Beta Catenin that is released into the cytoplasm after down regulation of E-Cadherin by MMP9 is translocated to the nucleus by IL8 (WNT pathway) (Tung-Yuan Lai, 2010). TNF and IL1B up regulate CXCR4 which facilitates movement of prostate cancer cells within the prostate and from the prostate to bone on lipid rafts (Han, 2001). These pro-inflammatory cytokines are more expressed among AAM. CONCLUSIONS Conclusion: These pro-inflammatory cytokines, the same cytokines identified in several other cancers and associated with aggressiveness and disease progression, are associated with PCa aggressiveness, disease progression and castrate resistant prostate cancer. These interactive pathways may become targets for therapy. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e856 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Isaac Powell More articles by this author Aliccia Bollig-Fischer More articles by this author Elisabeth Heath More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...