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dc.contributor.authorGrinde, Maria Tunset
dc.contributor.authorSkrbo, Nirma
dc.contributor.authorMoestue, Siver Andreas
dc.contributor.authorRødland, Einar Andreas
dc.contributor.authorBorgan, Eldrid
dc.contributor.authorKristian, Alexandr
dc.contributor.authorSitter, Beathe
dc.contributor.authorBathen, Tone
dc.contributor.authorBørresen-Dale, Anne-Lise
dc.contributor.authorMælandsmo, Gunhild
dc.contributor.authorSørlie, Therese
dc.contributor.authorMarangoni, Elisabetta
dc.contributor.authorGribbestad, Ingrid S
dc.date.accessioned2017-06-02T13:26:42Z
dc.date.available2017-06-02T13:26:42Z
dc.date.issued2014-01-21
dc.description.abstractIntroduction: Dysregulated choline metabolism is a well-known feature of breast cancer, but the underlying mechanisms are not fully understood. In this study, the metabolomic and transcriptomic characteristics of a large panel of human breast cancer xenograft models were mapped, with focus on choline metabolism. <br> Methods: Tumor specimens from 34 patient-derived xenograft models were collected and divided in two. One part was examined using high-resolution magic angle spinning (HR-MAS) MR spectroscopy while another part was analyzed using gene expression microarrays. Expression data of genes encoding proteins in the choline metabolism pathway were analyzed and correlated to the levels of choline (Cho), phosphocholine (PCho) and glycerophosphocholine (GPC) using Pearson’s correlation analysis. For comparison purposes, metabolic and gene expression data were collected from human breast tumors belonging to corresponding molecular subgroups. <br> Results: Most of the xenograft models were classified as basal-like (N = 19) or luminal B (N = 7). These two subgroups showed significantly different choline metabolic and gene expression profiles. The luminal B xenografts were characterized by a high PCho/GPC ratio while the basal-like xenografts were characterized by highly variable PCho/GPC ratio. Also, Cho, PCho and GPC levels were correlated to expression of several genes encoding proteins in the choline metabolism pathway, including choline kinase alpha (CHKA) and glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5). These characteristics were similar to those found in human tumor samples. <br> Conclusion: The higher PCho/GPC ratio found in luminal B compared with most basal-like breast cancer xenograft models and human tissue samples do not correspond to results observed from in vitro studies. It is likely that microenvironmental factors play a role in the in vivo regulation of choline metabolism. Cho, PCho and GPC were correlated to different choline pathway-encoding genes in luminal B compared with basal-like xenografts, suggesting that regulation of choline metabolism may vary between different breast cancer subgroups. The concordance between the metabolic and gene expression profiles from xenograft models with breast cancer tissue samples from patients indicates that these xenografts are representative models of human breast cancer and represent relevant models to study tumor metabolism in vivo.en_US
dc.descriptionSource at <a href=http://dx.doi.org/10.1186/bcr3597> http://dx.doi.org/10.1186/bcr3597 </a>.en_US
dc.identifier.citationGrinde et al.: Interplay of choline metabolites and genes in patient-derived breast cancer xenografts. Breast Cancer Research 2014 16:R5.en_US
dc.identifier.cristinIDFRIDAID 1098627
dc.identifier.doi10.1186/bcr3597
dc.identifier.issn1465-542X
dc.identifier.urihttps://hdl.handle.net/10037/11105
dc.language.isoengen_US
dc.publisherBioMed Centralen_US
dc.relation.journalBreast Cancer Research
dc.relation.projectIDeu-repo/grantAgreement/RCN/FRIMEDBIO/221879/Norway/Imaging the breast cancer metabolome//en_US
dc.relation.projectIDeu-repo/grantAgreement/RCN/BEHANDLING/218325/MetAction: Actionable Targets in Cancer Metastasis - from Bed to Bench to Byte to Bedside//en_US
dc.relation.projectIDeu-repo/grantAgreement/RCN/BEHANDLING/179571/Centre for Cancer Biomedicine, CCB//en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.titleInterplay of choline metabolites and genes in patient-derived breast cancer xenograftsen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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