Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7277
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dc.contributor.authorKadioglu, Onat-
dc.contributor.authorSaeed, Mohamed-
dc.contributor.authorMahmoud, Nuha-
dc.contributor.authorAzawi, Shaymaa-
dc.contributor.authorMrasek, Kristin-
dc.contributor.authorLiehr, Thomas-
dc.contributor.authorEfferth, Thomas-
dc.date.accessioned2022-07-04T07:21:38Z-
dc.date.available2022-07-04T07:21:38Z-
dc.date.issued2021-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/7291-
dc.description.abstractTP53 (p53) is a pivotal player in tumor suppression with fifty percent of all invasive tumors displaying mutations in the TP53 gene. In the present study, we characterized colon cancer cells (HCT116 p53 −/−) with TP53 deletion, a sub-line derived from HCT116-p53 +/+ cells. RNA sequencing and network analyses were performed to identify novel drug resistance mechanisms. Chromosomal aberrations were identified by multicolor fluorescence in situ hybridization (mFISH) and array comparative genomic hybridization (aCGH). Numerous genes were overexpressed in HCT116 p53 −/− cells: RND3/RhoE (235.6-fold up-regulated), DCLK1 (60.2-fold up-regulated), LBH (31.9-fold up-regulated), MYB (28.9-fold up-regulated), TACSTD2 (110.1-fold down-regulated), NRIP1 (81.5-fold down-regulated) and HLA-DMB (69.7-fold down-regulated) are among the identified genes with potential influence on multidrug resistance (MDR) and they are associated with cancer progression and tumorigenesis, according to previously published studies. Probably due to TP53 deletion, disturbances in DNA repair and apoptosis are leading to aberrancies in cellular and organismal organization, ultimately increasing tumorigenesis and cancer progression potential. With NFκB, PI3K and HSP70, being at the center of merged protein network, and TH1-2 pathways, being among the influenced pathways, it can be speculated that the inflammatory pathway contributes to a resistance phenotype together with cell cycle regulation and heat-shock response. HCT116-p53 −/− cells have more chromosomal aberrations, gains and losses in copy numbers than HCT116-p53 +/+ cells. In conclusion, numerous genomic aberrations, which might be associated with yet unknown drug resistance mechanisms, were identified. This may have important implications for future treatment strategies.en_GB
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleIdentification of potential novel drug resistance mechanisms by genomic and transcriptomic profiling of colon cancer cells with p53 deletionen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-7277-
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 09 Chemie, Pharmazie u. Geowissensch.de
jgu.organisation.number7950-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleArchives of toxicologyde
jgu.journal.volume95de
jgu.pages.start959de
jgu.pages.end974de
jgu.publisher.year2021-
jgu.publisher.nameSpringerde
jgu.publisher.placeBerlin u.a.de
jgu.publisher.issn1432-0738de
jgu.organisation.placeMainz-
jgu.subject.ddccode610de
jgu.publisher.doi10.1007/s00204-021-02979-4de
jgu.organisation.rorhttps://ror.org/023b0x485
Appears in collections:JGU-Publikationen

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