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.
- Abbott, D. W.; Freeman, M. L.; Holt, J. T. Double-strand break repair deficiency and radiation sensitivity in BRCA2 mutant cancer cells. J. Natl. Cancer Inst. 90:978–985; 1998. CrossRef
- Adem, C.; Soderberg, C. L.; Hafner, K., et al. ERBB2, TBX2, RPS6KB1, and MYC alterations in breast tissues of BRCA1 and BRCA2 mutation carriers. Genes Chromosomes Cancer 41:1–11; 2004. CrossRef
- Annab, L. A.; Terry, L.; Cable, P. L.; Brady, J.; Stampfer, M. R.; Barrett, J. C.; Afshari, C. A. Establishment and characterization of a breast cell strain containing a BRCA1 185delAG mutation. Gynecol. Oncol. 77:121–128; 2000. CrossRef
- Arason, A.; Jonasdottir, A.; Barkardottir, R. B.; Bergthorsson, J. T.; Teare, M. D.; Easton, D. F.; Egilsson, V. A population study of mutations and LOH at breast cancer gene loci in tumours from sister pairs: two recurrent mutations seem to account for all BRCA1/BRCA2 linked breast cancer in Iceland. J. Med. Genet. 35:446–449; 1998. CrossRef
- Bartek, J.; Taylor-Papadimitriou, J.; Miller, N.; Millis, R. Patterns of expression of keratin 19 as detected with monoclonal antibodies in human breast tissues and tumours. Int. J. Cancer 36:299–306; 1985.
- Briand, P.; Petersen, O. W.; Van Deurs, B. A new diploid nontumorigenic human breast epithelial cell line isolated and propagated in chemically defined medium. In Vitro Cell. Dev. Biol. 23A:181–188; 1987.
- Chambers, J. A.; Harris, A. Expression of the cystic fibrosis gene and the major pancreatic mucin gene, MUC1, in human ductal epithelial cells. J. Cell Sci. 105(Pt. 2):417–422; 1993.
- Daniels, M. J.; Wang, Y.; Lee, M.; Venkitaraman, A. R. Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2. Science 306:876–879; 2004. CrossRef
- Duensing, S.; Münger, K. The human papillomavirus type E6 and E7 onco-proteins independently induce numerical and structural chromosome instability. Cancer Res. 62:7075–7082; 2002.
- Fanjul, M.; Hollande, E. Morphogenesis of “duct-like” structures in three-dimensional cultures of human cancerous pancreatic duct cells (Capan-1). In Vitro Cell. Dev. Biol. 29A:574–584; 1993.
- Gasco, M.; Yulug, I. G.; Crook, T. TP53 mutations in familial breast cancer: functional aspects. Hum. Mutat. 21:301–306; 2003. CrossRef
- Gazdar, A. F.; Minna, J. D. NCI series of cell lines: an historical perspective. J. Cell. Biochem. Suppl. 24:1–11; 1996. CrossRef
- Goggins, M.; Schutte, M.; Lu, J., et al. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res. 56:5360–5364; 1996.
- Gretarsdottir, S.; Thorlacius, S.; Valgardsdottir, R., et al. BRCA2 and p53 mutations in primary breast cancer in relation to genetic instability. Cancer Res. 58:859–862; 1998.
- Gudjonsson, T.; Villadsen, R.; Nielsen, H. L.; Ronnov-Jessen, L.; Bissell, M. J.; Petersen, O. W. Isolation, immortalization, and characterization of a human breast epithelial cell line with stem cell properties. Genes Dev. 16:693–706; 2002. CrossRef
- Gudjonsson, T.; Villadsen, R.; Ronnov-Jessen, L.; Petersen, O. W. Immortalization protocols used in cell culture models of human breast morphogenesis. Cell. Mol. Life Sci. 61:2523–2534; 2004. CrossRef
- ISCN. An international system for human cytogenetic nomenclature. Mitelman, F. (Ed.). Basel: S. Karger, 1995.
- Johannsson, O.; Loman, N.; Moller, T.; Kristoffersson, U.; Borg, A.; Olsson, H. Incidence of malignant tumours in relatives of BRCA1 and BRCA2 germline mutation carriers. Eur. J. Cancer 35:1248–1257; 1999. CrossRef
- Johannsson, O. T.; Staff, S.; Vallon-Christerssen, J., et al. Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier. Lab. Invest. 83:387; 2003.
- King, M. C.; Marks, J. H.; Mandell, J. B.; New York Breast Cancer Study Group. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302:643–646; 2003. CrossRef
- Lacroix, M.; Leclercq, G. Relevance of breast cancer cell lines as models for breast tumours: an update. Breast Cancer Res. Treat. 83:249–289; 2004. CrossRef
- Marmorstein, L. Y.; Ouchi, T.; Aaronson, S. A. The BRCA2 gene product functionally interacts with p53 and RAD51. Proc. Natl. Acad. Sci. USA 95:13869–13874; 1998. CrossRef
- Mikaelsdottir, E. K.; Valgeirsdottir, S.; Eyfjord, J. E.; Rafnar, T. The Icelandic founder mutation BRCA2 999del5: analysis of expression. Breast Cancer Res. 6:284–290; 2004. CrossRef
- Moynahan, M. E.; Pierce, A. J.; Jasin, M. BRCA2 is required for homologydirected repair of chromosomal breaks. Mol. Cell 7:263–272; 2001. CrossRef
- Narod, S. A.; Foulkes, W. D. BRCA1 and BRCA2: 1994 and beyond. Nat. Rev. Cancer 4:665–676; 2004. CrossRef
- Pechoux, C.; Gudjonsson, T.; Ronnov-Jessen, L.; Bissell, M. J.; Petersen, O. W. Human mammary luminal epithelial cells contain progenitors to myoepithelial cells. Dev. Biol. 206:88–99; 1999. CrossRef
- Provencher, D. M.; Lounis, H.; Champoux, L., et al. Characterization of four novel epithelial ovarian cancer cell lines. In Vitro Cell. Dev. Biol. 36A:357–361; 2000. CrossRef
- Samouelian, V.; Maugard, C. M.; Jolicoeur, M.; Bertrand, R.; Arcand, S. L.; Tonin, P. N.; Provencher, D. M.; Mes-Masson, A. M. Chemosensitivity and radiosensitivity profiles of four new human epithelial ovarian cancer cell lines exhibiting genetic alterations in BRCA2, TGFbeta-RII, KRAS2, TP53 and/or CDNK2A. Cancer Chemother. Pharmacol. 54:497–504; 2004. CrossRef
- Sigurdsson, S.; Thorlacius, S.; Tomasson, J.; Tryggvadottir, L.; Benediktsdottir, K.; Eyfjord, J. E.; Jonsson, E. BRCA2 mutation in Icelandic prostate cancer patients. J. Mol. Med. 75:758–761; 1997. CrossRef
- Spain, B. H.; Larson, C. J.; Shihabuddin, L. S.; Gage, F. H.; Verma, I. M. Truncated BRCA2 is cytoplasmic: implications for cancer-linked mutations. Proc. Natl. Acad. Sci. USA 96:13920–13925; 1999. CrossRef
- Thorlacius, S.; Olafsdottir, G.; Tryggvadottir, L., et al. A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes. Nat. Genet. 13:117–119; 1996. CrossRef
- Thorlacius, S.; Struewing, J. P.; Hartge, P., et al. Population-based study of risk of breast cancer in carriers of BRCA2 mutation. Lancet 352:1337–1339; 1998. CrossRef
- Tomlinson, G. E.; Chen, T. T.; Stastny, V. A., et al. Characterization of a breast cancer cell line derived from a germ-line BRCA1 mutation carrier. Cancer Res. 58:3237–3242; 1998.
- Tonin, P. N.; Hudson, T. J.; Rodier, F., et al. Microarray analysis of gene expression mirrors the biology of an ovarian cancer model. Oncogene 20:6617–6626; 2001. CrossRef
- Venkitaraman, A. R. Tracing the network connecting BRCA and Fanconi anaemia proteins. Nat. Rev. Cancer 4:266–276; 2004. CrossRef
- Warren, M.; Lord, C. J.; Masabanda, J.; Griffin, D.; Ashworth, A. Phenotypic effects of heterozygosity for a BRCA2 mutation. Hum. Mol. Genet. 12:2645–2656; 2003. CrossRef
- Wistuba, I. I.; Bryant, D.; Behrens, C.; Milchgrub, S.; Virmani, A. K.; Ashfaq, R.; Minna, J. D.; Gazdar, A. F. Comparison of features of human lung cancer cell lines and their corresponding tumors. Clin. Cancer Res. 5:991–1000; 1999.
- Yuan, S. S.; Lee, S. Y.; Chen, G.; Song, M.; Tomlinson, G. E.; Lee, E. Y. BRCA2 is required for ionizing radiation-induced assembly of Rad51 complex in vivo. Cancer Res. 59:3547–3551; 1999.
- Establishment of three human breast epithelial cell lines derived from carriers of the 999del5 BRCA2 icelandic founder mutation
In Vitro Cellular & Developmental Biology - Animal
Volume 41, Issue 10 , pp 337-342
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- breast cancer
- cell lines
- 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