Show simple item record

dc.contributor.authorCampa Fernández, Víctor Manuel
dc.contributor.authorBaltziskueta, Eder
dc.contributor.authorBengoa Vergniory, Nora
dc.contributor.authorGorroño Etxebarria, Irantzu
dc.contributor.authorWesołowski, Radosław
dc.contributor.authorWaxman, Jonathan
dc.contributor.authorKypta, Robert M.
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.description.abstractExpression of Glycogen Synthase Kinase-3 (GSK-3) is elevated in prostate cancer and its inhibition reduces prostate cancer cell proliferation, in part by reducing androgen receptor (AR) signaling. However, GSK-3 inhibition can also activate signals that promote cell proliferation and survival, which may preclude the use of GSK-3 inhibitors in the clinic. To identify such signals in prostate cancer, we screened for changes in transcription factor target DNA binding activity in GSK-3-silenced cells. Among the alterations was a reduction in AR DNA target binding, as predicted from previous studies, and an increase in NFκB DNA target binding. Consistent with the latter, gene silencing of GSK-3 or inhibition using the GSK-3 inhibitor CHIR99021 increased basal NFκB transcriptional activity. Activation of NFκB was accompanied by an increase in the level of the NFκB family member RelB. Conversely, silencing RelB reduced activation of NFκB by CHIR99021. Furthermore, the reduction of prostate cancer cell proliferation by CHIR99021 was potentiated by inhibition of NFκB signaling using the IKK inhibitor PS1145. Finally, stratification of human prostate tumor gene expression data for GSK3 revealed an inverse correlation between NFκB-dependent and androgen-dependent gene expression, consistent with the results from the transcription factor target DNA binding screen. In addition, there was a correlation between expression of androgen-repressed NFκB target genes and reduced survival of patients with metastatic prostate cancer. These findings highlight an association between GSK-3/AR and NFκB signaling and its potential clinical importance in metastatic prostate cancer.es_ES
dc.format.extent15 p.es_ES
dc.publisherImpact Journalses_ES
dc.rightsAtribución 3.0 España*
dc.sourceOncotarget. 2014 Sep 30;5(18):8173-87es_ES
dc.subject.otherProstate canceres_ES
dc.subject.otherGlycogen synthase kinase-3es_ES
dc.subject.otherAndrogen receptores_ES
dc.subject.otherNFĸB transcription factores_ES
dc.subject.otherWnt signalinges_ES
dc.titleA screen for transcription factor targets of glycogen synthase kinase-3 highlights an inverse correlation of NFκB and androgen receptor signaling in prostate canceres_ES

Files in this item


This item appears in the following Collection(s)

Show simple item record

Atribución 3.0 EspañaExcept where otherwise noted, this item's license is described as Atribución 3.0 España