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dc.contributor.authorBraadland, Pederen_US
dc.contributor.authorGrytli, Helene Hartvedten_US
dc.contributor.authorRamberg, Håkon Andreen_US
dc.contributor.authorKatz, Betinaen_US
dc.contributor.authorKellmann, Ralfen_US
dc.contributor.authorGauthier-Landry, louisen_US
dc.contributor.authorFazli, Ladanen_US
dc.contributor.authorKrobert, Kurt Allenen_US
dc.contributor.authorWang, Wanzhongen_US
dc.contributor.authorLevy, Finn Olaven_US
dc.contributor.authorBjartell, Andersen_US
dc.contributor.authorBerge, Viktoren_US
dc.contributor.authorRennie, Paul S.en_US
dc.contributor.authorMellgren, Gunnaren_US
dc.contributor.authorMælandsmo, Gunhilden_US
dc.contributor.authorSvindland, Auden_US
dc.contributor.authorBarbier, Olivieren_US
dc.contributor.authorTasken, Kristin Austliden_US
dc.PublishedOncoTarget 2016, 7(2):1878-1894eng
dc.description.abstractThe underlying mechanisms responsible for the development of castration-resistant prostate cancer (CRPC) in patients who have undergone androgen deprivation therapy are not fully understood. This is the first study to address whether β2-adrenergic receptor (ADRB2)- mediated signaling may affect CRPC progression in vivo. By immunohistochemical analyses, we observed that low levels of ADRB2 is associated with a more rapid development of CRPC in a Norwegian patient cohort. To elucidate mechanisms by which ADRB2 may affect CRPC development, we stably transfected LNCaP cells with shRNAs to mimic low and high expression of ADRB2. Two UDP-glucuronosyltransferases, UGT2B15 and UGT2B17, involved in phase II metabolism of androgens, were strongly downregulated in two LNCaP shADRB2 cell lines. The low-ADRB2 LNCaP cell lines displayed lowered glucuronidation activities towards androgens than high-ADRB2 cells. Furthermore, increased levels of testosterone and enhanced androgen responsiveness were observed in LNCaP cells expressing low level of ADRB2. Interestingly, these cells grew faster than high-ADRB2 LNCaP cells, and sustained their low glucuronidation activity in castrated NOD/SCID mice. ADRB2 immunohistochemical staining intensity correlated with UGT2B15 staining intensity in independent TMA studies and with UGT2B17 in one TMA study. Similar to ADRB2, we show that low levels of UGT2B15 are associated with a more rapid CRPC progression. We propose a novel mechanism by which ADRB2 may affect the development of CRPC through downregulation of UGT2B15 and UGT2B17.en_US
dc.publisherImpact Journalseng
dc.rightsAttribution CC BYeng
dc.subjectβ2-adrenergic receptoreng
dc.titleLow β2-adrenergic receptor level may promote development of castration resistant prostate cancer and altered steroid metabolismen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2016 Impact Journals, LLC
dc.relation.projectStiftelsen Kristian Gerhard Jebsen: SKGJ-MED-005

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Attribution CC BY
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