?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F13517%2F&rft.title=Sex+Hormone+Modulation+of+HHV-8+Transcription&rft.creator=COMPAORE%2C+TEGWINDE+REBECA&rft.description=Human+herpesvirus+8+(HHV-8)+seroprevalence+is+similar+in+men+and+women%2C+but+Kaposi%E2%80%99s+sarcoma+(KS)+is+mostly+seen+in+men%2C+suggesting+that+sex+hormones+play+a+role+in+KS+development.+Previous+work+from+our+laboratory+has+identified+potential+estrogen+response+elements+(EREs)+within+several+regulatory+genes%E2%80%99+promoters+such+as+K8+(KB-Zip)%2C+ORF50+and+ORF49.+++The+HHV-8+EREs+were+found+to+bind+the+alpha+estrogen+receptor.+The+functionality+of+the+K8+EREs+was+demonstrated+using+transient+expression+assays.%0D%0AIn+this+study%2C+we+tested+the+hypothesis+that+estrogen+modulates+the+transcription+of+HHV-8+during+latency+or+reactivation.%0D%0A+++++BCBL-1+cells+are+a+B+established+from+a+pleural+effusion+lymphoma+that+is+HHV-8+positive+and+Epstein-Barr+virus+(EBV)+negative+were+used+in+the+current+study.+Trex-BCBL-1+cells+contain+a+doxycycline+inducible+ORF50+gene.+MCF-7+cells+are+well+studied+breast+cancer+cell+line.+Production+of+infectious+virus+was+determined+using+a+TCID50+assay.+Transcription+of+individual+viral+genes+was+measure+by+RT-PCR+using+specific+primers.+Measurement+of+cellular+transcription+following+estrogen+treatment+was+performed+using+estrogen+signaling+PCR+arrays.%0D%0A+++++Treatment+of+BCBL-1+or+TRex-BCBL-1+cells+with+estrogen+did+not+result+in+viral+reactivation+as+measure+by+flow+cytometry.+Estrogen+treatment+did+not+prevent+TPA-induced+reactivation+of+BCBL-1+cells+or+doxycycline-induced+reactivation+of+TRex-BCBL-1+cells.+treatment+of+BCBL-1+cells+with+estrogen+alone+resulted+in+a+decrease+of+constitutive+viral+transcription.+BCBL-1+express+estrogen+receptor+beta+(compared+to+MCF-7+cells+which+express+estrogen+receptor+alpha).Treatment+of+MCF-7+cells+with+estrogen+result+in+an+increase+in+transcription+of+cellular+genes+while+treatment+of+BCBL-1+resulted+in+a+decrease+in+cellular+transcription.%0D%0A+++++Our+results+suggest+that+estrogen+can+down-regulate+both+cellular+and+viral+transcription+in+B+cells.+This+down+regulation+may+be+involved+in+the+lack+of+KS+development+in+women.++%0D%0A+++++Statement+of+Public+Health+relevance%3A++Reactivation+of+HHV-8+has+been+shown+to+be+associated+with+the+advent+of+Kaposi%E2%80%99s+sarcoma.+By+determining+the+role+of+estrogen+in+the+transcription+of+viral+genes+and+the+estrogen+receptors+involved%2C+potential+therapeutic+target+can+be+found.+The+results+from+these+experiments+will+help+understand+the+biology+of+HHV-8%2C+and+pathology+of+Kaposi%E2%80%99s+sarcoma.&rft.date=2012-09-24&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F13517%2F1%2FTEGWINDE_R_COMPAORE_ETD_2012.pdf&rft.identifier=++COMPAORE%2C+TEGWINDE+REBECA++(2012)+Sex+Hormone+Modulation+of+HHV-8+Transcription.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++