Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier

2.50
Hdl Handle:
http://hdl.handle.net/2336/4593
Title:
Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier
Authors:
Johannsson, Oskar T; Staff, Synnöve; Vallon-Christersson, Johan; Kytöla, Soili; Gudjonsson, Thorarinn; Rennstam, Karin; Hedenfalk, Ingrid A; Adeyinka, Adewale; Kjellén, Elisabeth; Wennerberg, Johan; Baldetorp, Bo; Petersen, Ole W; Olsson, Håkan; Oredsson, Stina; Isola, Jorma; Borg, Ake
Citation:
Lab. Invest. 2003, 83(3):387-96
Issue Date:
1-Mar-2003
Abstract:
A human tumor xenograft (L56Br-X1) was established from a breast cancer axillary lymph node metastasis of a 53-year-old woman with a BRCA1 germ-line nonsense mutation (1806C>T; Q563X), and a cell line (L56Br-C1) was subsequently derived from the xenograft. The xenograft carries only the mutant BRCA1 allele and expresses mutant BRCA1 mRNA but no BRCA1 protein as determined by immunoprecipitation or Western blotting. The primary tumor, lymph node metastasis, and xenograft were hypodiploid by DNA flow cytometry, whereas the cell line displayed an aneuploidy apparently developed via polyploidization. Cytogenetic analysis, spectral karyotyping, and comparative genomic hybridization of the cell line revealed a highly complex karyotype with numerous unbalanced translocations. The xenograft and cell line had retained a somatic TP53 missense mutation (S215I) originating from the primary tumors, as well as a lack of immunohistochemically detectable expression of steroid hormone receptors, epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER-2), and keratin 8. Global gene expression analysis by cDNA microarrays supported a correlation between the expression profiles of the primary tumor, lymph node metastasis, xenograft, and cell line. We conclude that L56Br-X1 and L56Br-C1 are useful model systems for studies of the pathogenesis and new therapeutic modalities of BRCA1-induced human breast cancer.
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Full metadata record

DC FieldValue Language
dc.contributor.authorJohannsson, Oskar T-
dc.contributor.authorStaff, Synnöve-
dc.contributor.authorVallon-Christersson, Johan-
dc.contributor.authorKytöla, Soili-
dc.contributor.authorGudjonsson, Thorarinn-
dc.contributor.authorRennstam, Karin-
dc.contributor.authorHedenfalk, Ingrid A-
dc.contributor.authorAdeyinka, Adewale-
dc.contributor.authorKjellén, Elisabeth-
dc.contributor.authorWennerberg, Johan-
dc.contributor.authorBaldetorp, Bo-
dc.contributor.authorPetersen, Ole W-
dc.contributor.authorOlsson, Håkan-
dc.contributor.authorOredsson, Stina-
dc.contributor.authorIsola, Jorma-
dc.contributor.authorBorg, Ake-
dc.date.accessioned2006-09-25T11:30:34Z-
dc.date.available2006-09-25T11:30:34Z-
dc.date.issued2003-03-01-
dc.identifier.citationLab. Invest. 2003, 83(3):387-96en
dc.identifier.issn0023-6837-
dc.identifier.pmid12649339-
dc.identifier.otherMAO12-
dc.identifier.urihttp://hdl.handle.net/2336/4593-
dc.description.abstractA human tumor xenograft (L56Br-X1) was established from a breast cancer axillary lymph node metastasis of a 53-year-old woman with a BRCA1 germ-line nonsense mutation (1806C>T; Q563X), and a cell line (L56Br-C1) was subsequently derived from the xenograft. The xenograft carries only the mutant BRCA1 allele and expresses mutant BRCA1 mRNA but no BRCA1 protein as determined by immunoprecipitation or Western blotting. The primary tumor, lymph node metastasis, and xenograft were hypodiploid by DNA flow cytometry, whereas the cell line displayed an aneuploidy apparently developed via polyploidization. Cytogenetic analysis, spectral karyotyping, and comparative genomic hybridization of the cell line revealed a highly complex karyotype with numerous unbalanced translocations. The xenograft and cell line had retained a somatic TP53 missense mutation (S215I) originating from the primary tumors, as well as a lack of immunohistochemically detectable expression of steroid hormone receptors, epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER-2), and keratin 8. Global gene expression analysis by cDNA microarrays supported a correlation between the expression profiles of the primary tumor, lymph node metastasis, xenograft, and cell line. We conclude that L56Br-X1 and L56Br-C1 are useful model systems for studies of the pathogenesis and new therapeutic modalities of BRCA1-induced human breast cancer.en
dc.language.isoenen
dc.publisherLippincott Williams & Wilkinsen
dc.relation.urlhttp://proquest.umi.com/pqdlink?index=3&did=984461231&SrchMode=3&sid=1&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1159183776&clientId=58120&aid=1en
dc.subject.meshAneuploidyen
dc.subject.meshBreast Neoplasmsen
dc.subject.meshCarcinoma, Ductal, Breasten
dc.subject.meshCodon, Nonsenseen
dc.subject.meshDNA, Neoplasm/analysisen
dc.subject.meshFemaleen
dc.subject.meshFlow Cytometryen
dc.subject.meshGenes, BRCA1en
dc.subject.meshGerm-Line Mutationen
dc.subject.meshHeterozygoteen
dc.subject.meshHumansen
dc.subject.meshLymph Nodesen
dc.subject.meshLymphatic Metastasisen
dc.subject.meshNucleic Acid Hybridizationen
dc.subject.meshResearch Support, Non-U.S. Gov'ten
dc.subject.meshSpectral Karyotypingen
dc.subject.meshTranslocation, Geneticen
dc.subject.meshTransplantation, Heterologousen
dc.subject.meshTumor Cells, Cultureden
dc.subject.meshTumor Markers, Biologicalen
dc.titleCharacterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrieren
dc.typeArticleen
dc.format.digYES-

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