{"doi":"10.1002/nbm.1318","title":"Characterization of breast cancers and therapy response by MRS and quantitative gene expression profiling in the choline pathway","abstract":"<jats:title>Abstract</jats:title><jats:p>Tumor choline metabolites have potential for use as diagnostic indicators of breast cancer phenotype and can be non‐invasively monitored <jats:italic>in vivo</jats:italic> by MRS. Extract studies have determined that the principle diagnostic component of these peaks is phosphocholine (PCho), the biosynthetic precursor to the membrane phospholipid, phosphatidylcholine (PtdCho). The ability to resolve and quantify PCho <jats:italic>in vivo</jats:italic> would improve the accuracy of this putative diagnostic tool. In addition, determining the biochemical mechanisms underlying these metabolic perturbations will improve the understanding of breast cancer and may suggest potential molecular targets for drug development. Reported herein is the <jats:italic>in vivo</jats:italic> resolution and quantification of PCho and glycerophosphocholine (GPC) in breast cancer xenografts in SCID mice via image‐guided <jats:sup>31</jats:sup>P MRS, localized to a single voxel. Tumor metabolites are also detected using <jats:italic>ex vivo</jats:italic> extracts and high‐resolution NMR spectroscopy and are quantified in the metastatic tumor line, MDA‐mb‐231. Also reported is the quantification of cytosolic and lipid metabolites in breast cells of differing cancer phenotype, and the identification of metabolites that differ among these cell lines. In cell extracts, PCho and the PtdCho breakdown products, lysophosphatidylcholine, GPC and glycerol 3‐phosphate, are all raised in breast cancer lines relative to an immortalized non‐malignant line. These metabolic differences are in direct agreement with differences in expression of genes encoding enzymes in the choline metabolic pathway. Results of this study are consistent with previous studies, which have concluded that increased choline uptake, increased choline kinase activity, and increased phosholipase‐mediated turnover of PtdCho contribute to the observed increase in PCho in breast cancer. In addition, this study presents evidence suggesting a specific role for phospholipase A<jats:sub>2</jats:sub>‐mediated PtdCho catabolism. Gene expression changes following taxane therapy are also reported and are consistent with previously reported changes in choline metabolites after the same therapy in the same tumor model. Copyright © 2008 John Wiley &amp; Sons, Ltd.</jats:p>","journal":"NMR in Biomedicine","year":2009,"id":35432,"datarank":2.6610032434724427,"base_score":3.828641396489095,"endowment":3.828641396489095,"self_citation_contribution":0.5742962094733643,"citation_network_contribution":2.0867070339990783,"self_endowment_contribution":0.5742962094733643,"citer_contribution":2.0867070339990783,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":43,"citers_with_citation_signal":38,"citers_with_endowment":38,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":181486,"name":"Danielle Carroll","orcid":null,"position":1,"is_corresponding":false},{"id":181487,"name":"Sam Day","orcid":null,"position":2,"is_corresponding":false},{"id":181488,"name":"Heather Gray","orcid":null,"position":3,"is_corresponding":false},{"id":181489,"name":"Pooja Sadarangani","orcid":null,"position":4,"is_corresponding":false},{"id":181490,"name":"Shiva Murthi","orcid":null,"position":5,"is_corresponding":false},{"id":181491,"name":"Constantin Job","orcid":null,"position":6,"is_corresponding":false},{"id":181492,"name":"Brenda Baggett","orcid":null,"position":7,"is_corresponding":false},{"id":181493,"name":"Natarajan Raghunand","orcid":null,"position":8,"is_corresponding":false},{"id":65782,"name":"Robert J. Gillies","orcid":"0000-0002-8888-7747","position":9,"is_corresponding":false},{"id":181485,"name":"David L. Morse","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.828641396489095,"endowment":3.828641396489095,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19016452","pmcid":"PMC4130559","openalex_id":"https://openalex.org/W1983177576","authors":[],"funders":[{"funder_name":"NIH","grant_id":"R24 CA83148","title":null},{"funder_name":"NIH","grant_id":"R01 CA80130","title":null},{"funder_name":"NIH","grant_id":"R01 CA77575","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA088285","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA88285","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA077575","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA125627","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R24 CA083148","title":null}],"total_grants":8,"fwci":4.9076,"citation_percentile":0.94646257,"influential_citations":1,"citation_trend":[{"year":2012,"count":7},{"year":2013,"count":5},{"year":2014,"count":5},{"year":2015,"count":1},{"year":2016,"count":1},{"year":2017,"count":1},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2024,"count":1}],"oa_status":"green","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4130559","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc4130559?pdf=render","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4130559","host_type":"repository"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fnbm.1318","host_type":"publisher"},{"url":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/pdf/10.1002/nbm.1318","host_type":"publisher"},{"url":"https://doi.org/10.1002/nbm.1318","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19016452","host_type":"repository"}],"fields_of_study":["Advanced MRI Techniques and Applications","Metabolomics and Mass Spectrometry Studies","Advanced NMR Techniques and Applications","Biology","Medicine","Animals","Cell Extracts","Cell Line, Tumor","Choline","Docetaxel","Gene Expression Profiling","Gene Expression Regulation, Neoplastic","Genes, Neoplasm","Humans","Magnetic Resonance Spectroscopy","Mammary Neoplasms, Animal","Metabolic Networks and Pathways","Mice","Mice, SCID","Phenotype","Phosphatidylcholines","RNA, Messenger","Taxoids","Xenograft Model Antitumor Assays"],"mesh_terms":["Docetaxel","Animals","Cell Extracts","Choline","Humans","Magnetic Resonance Spectroscopy","Phenotype","Phosphatidylcholines","RNA, Messenger","Mammary Neoplasms, Animal","Gene Expression Regulation, Neoplastic","Mice, SCID","Gene Expression Profiling","Xenograft Model Antitumor Assays","Taxoids","Cell Line, Tumor","Mice","Genes, Neoplasm","Metabolic Networks and Pathways"],"keywords":["Phosphocholine","Choline kinase","Choline","In vivo","Lysophosphatidylcholine","Breast cancer","Phosphatidylcholine","Ex vivo","Biology","Cancer research","Biochemistry","Chemistry","Phospholipid","Cancer","Membrane"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T03:56:13.260737Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}