Article
Lab Invest 2003, 83:387–396
Characterization of a Novel Breast Carcinoma Xenograft and Cell Line Derived from a BRCA1 Germ-Line Mutation Carrier
Inquiries about the cell line should be addressed to Stina Oredsson, Department of Cell and Organism Biology, Lund University, Lund, Sweden. E-mail: stina.oredsson@cob.lu.se.
Oskar T Johannsson1, Synnöve Staff5, Johan Vallon-Christersson1, Soili Kytöla6, Thorarinn Gudjonsson7, Karin Rennstam1, Ingrid A Hedenfalk1, Adewale Adeyinka3, Elisabeth Kjellén1, Johan Wennerberg2, Bo Baldetorp1, Ole W Petersen7, Håkan Olsson1, Stina Oredsson4, Jorma Isola1,5 and Åke Borg1
- 1Department of Oncology, University Hospital, Lund, Sweden
- 2Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital, Lund, Sweden
- 3Department of Clinical Genetics, University Hospital, Lund, Sweden
- 4Department of Cell and Organism Biology, Lund University, Lund, Sweden
- 5Laboratory of Cancer Biology, Institute of Medical Technology, Tampere University and University Hospital, Tampere, Finland
- 6Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
- 7Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
Correspondence: Dr. Oskar T. Johannsson, Department of Medical Oncology, University Hospital of Iceland, Reykjavik, Iceland. E-mail: oskarjoh@landspitali.is
Received 16 December 2002.
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.
