Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-220
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dc.contributor.authorJuengel, Eva-
dc.contributor.authorNatsheh, Iyad-
dc.contributor.authorNajafi, Ramin-
dc.contributor.authorRutz, Jochen-
dc.contributor.authorTsaur, Igor-
dc.contributor.authorHaferkamp, Axel-
dc.contributor.authorChun, Felix K.-H.-
dc.contributor.authorBlaheta, Roman A.-
dc.date.accessioned2019-11-08T09:30:25Z-
dc.date.available2019-11-08T10:30:25Z-
dc.date.issued2019-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/222-
dc.description.abstractBackground: Although mechanistic target of rapamycin (mTOR) inhibitors, such as temsirolimus, show promise in treating bladder cancer, acquired resistance often hampers efficacy. This study evaluates mechanisms leading to resistance. Methods: Cell growth, proliferation, cell cycle phases, and cell cycle regulating proteins were compared in temsirolimus resistant (res) and sensitive (parental—par) RT112 and UMUC3 bladder cancer cells. To evaluate invasive behavior, adhesion to vascular endothelium or to immobilized extracellular matrix proteins and chemotactic activity were examined. Integrin α and β subtypes were analyzed and blocking was done to evaluate physiologic integrin relevance. Results: Growth of RT112res could no longer be restrained by temsirolimus and was even enhanced in UMUC3res, accompanied by accumulation in the S- and G2/M-phase. Proteins of the cdk-cyclin and Akt-mTOR axis increased, whereas p19, p27, p53, and p73 decreased in resistant cells treated with low-dosed temsirolimus. Chemotactic activity of RT112res/UMUC3res was elevated following temsirolimus re-exposure, along with significant integrin α2, α3, and β1 alterations. Blocking revealed a functional switch of the integrins, driving the resistant cells from being adhesive to being highly motile. Conclusion: Temsirolimus resistance is associated with reactivation of bladder cancer growth and invasive behavior. The α2, α3, and β1 integrins could be attractive treatment targets to hinder temsirolimus resistance.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin-
dc.language.isoeng-
dc.rightsCC BYde_DE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleMechanisms behind temsirolimus resistance causing reactivated growth and invasive behavior of bladder cancer cells in vitroen_GB
dc.typeZeitschriftenaufsatzde_DE
dc.identifier.doihttp://doi.org/10.25358/openscience-220-
jgu.type.dinitypearticle-
jgu.type.versionPublished versionen_GB
jgu.type.resourceText-
jgu.organisation.departmentFB 04 Medizin-
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleCancers-
jgu.journal.volume11-
jgu.journal.issue6-
jgu.pages.alternativeArt. 777-
jgu.publisher.year2019-
jgu.publisher.nameMDPI-
jgu.publisher.placeBasel-
jgu.publisher.urihttp://dx.doi.org/10.3390/cancers11060777-
jgu.publisher.issn2072-6694-
jgu.organisation.placeMainz-
jgu.subject.ddccode610-
opus.date.accessioned2019-11-08T09:30:25Z-
opus.date.modified2019-11-14T09:09:28Z-
opus.date.available2019-11-08T10:30:25-
opus.subject.dfgcode04-205-
opus.organisation.stringFB 04: Medizin: Klinik und Poliklinik für Urologie und Kinderurologiede_DE
opus.identifier.opusid59403-
opus.institute.number0482-
opus.metadataonlyfalse-
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_GB
opus.affiliatedJuengel, Eva-
opus.affiliatedTsaur, Igor-
opus.affiliatedHaferkamp, Axel-
jgu.publisher.doi10.3390/cancers11060777
jgu.organisation.rorhttps://ror.org/023b0x485
Appears in collections:JGU-Publikationen

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