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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.authorEngebråten, Olav
dc.contributor.authorSørlie, Therese
dc.contributor.authorMarangoni, Elisabetta
dc.contributor.authorGribbestad, Ingrid S
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. 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. 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. 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.nb_NO
dc.publisherBioMed Centralnb_NO
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleInterplay of choline metabolites and genes in patient-derived breast cancer xenograftsnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.source.journalBreast Cancer Researchnb_NO
dc.relation.projectNorges forskningsråd: 221879nb_NO
dc.relation.projectNorges forskningsråd: 218325nb_NO
dc.relation.projectNorges forskningsråd: 179571nb_NO
dc.description.localcode© 2014 Grinde et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the CreativeCommons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.nb_NO
cristin.unitnameInstitutt for sirkulasjon og bildediagnostikk
cristin.unitnameFakultet for teknologi

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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal