NOVEMBER/DECEMBER 2005, Volume 41, Issue 10, pp 337-342
Establishment of three human breast epithelial cell lines derived from carriers of the 999del5 BRCA2 icelandic founder mutation
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Germ line mutations in BRCA1 and BRCA2 account for a large proportion of inherited breast and ovarian cancer. Both genes are involved in DNA repair by homologous recombination and are thought to play a vital role in maintaining genomic stability. A major drawback for long-term functional studies of BRCA in general and BRCA2 in particular has been a lack of representative human breast epithelial cell lines. In the present study, we have established three cell lines from two patients harboring the 999del5 germ line founder mutation in the BRCA2 gene. Primary cultures were established from cellular outgrowth of explanted tissue and subsequently transfected with a retroviral construct containing the HPV-16 E6 and E7 oncogenes. Paired cancer-derived and normal-derived cell lines were established from one patient referred to as BRCA2-999del5-2T and BRCA2-999del5-2N, respectively. In addition, one cell line was derived from cancer-associated normal tissue from another patient referred to as BRCA2-999del5-1N. All three cell lines showed characteristics of breast epithelial cells as evidenced by expression of breast epithelial specific cytokeratins. Cytogenetic analysis showed marked chromosomal instability with tetraploidy and frequent telomeric association. In conclusion, we have established three breast cpithelial cell lines from two patients carrying the BRCA2 Icelandic 999del5 founder mutation. These cell lines from the basis for further studies on carcinogenesis and malignant progression of breast cancer on a defined genetic background.
Agla J. Rubner Fridriksdottir and Thorarinn Gudjonsson contributed equally to this study.
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- Establishment of three human breast epithelial cell lines derived from carriers of the 999del5 BRCA2 icelandic founder mutation
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Volume 41, Issue 10 , pp 337-342
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- breast cancer
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- BRCA2 mutation
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- Author Affiliations
- 1. Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- 2. Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Skogarhlid 8, IS-105, Reykjavik, Iceland
- 3. Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland
- 4. Chromosome Laboratory, Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland
- 5. Department of Oncology, Landspitali University Hospital, Reykjavik, Iceland