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Article

Establishment and Characterization of a Brca1−/−, p53−/− Mouse Mammary Tumor Cell Line

1
Institute of Enzymology, Research Centre for Natural Sciences, 1117 Budapest, Hungary
2
Institute of Cancer Research, Medical University of Vienna, 1090 Vienna, Austria
3
Central Hospital of Southern Pest—National Institute of Hematology and Infectious Diseases, 1097 Budapest, Hungary
4
Department of Experimental Pharmacology, National Institute of Oncology, 1122, Budapest, Hungary
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(4), 1185; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041185
Received: 30 December 2019 / Revised: 25 January 2020 / Accepted: 1 February 2020 / Published: 11 February 2020
(This article belongs to the Special Issue Genetically Engineered Mice to Study Cancer)
Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. By the age of 80, the estimated risk for breast cancer for women with germline BRCA1 or BRCA2 mutations is around 80%. Genetically engineered BRCA1-deficient mouse models offer a unique opportunity to study the pathogenesis and therapy of triple negative breast cancer. Here we present a newly established Brca1−/−, p53−/− mouse mammary tumor cell line, designated as CST. CST shows prominent features of BRCA1-mutated triple-negative breast cancers including increased motility, high proliferation rate, genome instability and sensitivity to platinum chemotherapy and PARP inhibitors (olaparib, veliparib, rucaparib and talazoparib). Genomic instability of CST cells was confirmed by whole genome sequencing, which also revealed the presence of COSMIC (Catalogue of Somatic Mutations in Cancer) mutation signatures 3 and 8 associated with homologous recombination (HR) deficiency. In vitro sensitivity of CST cells was tested against 11 chemotherapy agents. Tumors derived from orthotopically injected CST-mCherry cells in FVB-GFP mice showed sensitivity to cisplatin, providing a new model to study the cooperation of BRCA1-KO, mCherry-positive tumor cells and the GFP-expressing stromal compartment in therapy resistance and metastasis formation. In summary, we have established CST cells as a new model recapitulating major characteristics of BRCA1-negative breast cancers. View Full-Text
Keywords: breast cancer; BRCA1; cancer cell line; genetically engineered mouse model breast cancer; BRCA1; cancer cell line; genetically engineered mouse model
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MDPI and ACS Style

Hámori, L.; Kudlik, G.; Szebényi, K.; Kucsma, N.; Szeder, B.; Póti, Á.; Uher, F.; Várady, G.; Szüts, D.; Tóvári, J.; Füredi, A.; Szakács, G. Establishment and Characterization of a Brca1−/−, p53−/− Mouse Mammary Tumor Cell Line. Int. J. Mol. Sci. 2020, 21, 1185. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041185

AMA Style

Hámori L, Kudlik G, Szebényi K, Kucsma N, Szeder B, Póti Á, Uher F, Várady G, Szüts D, Tóvári J, Füredi A, Szakács G. Establishment and Characterization of a Brca1−/−, p53−/− Mouse Mammary Tumor Cell Line. International Journal of Molecular Sciences. 2020; 21(4):1185. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041185

Chicago/Turabian Style

Hámori, Lilla, Gyöngyi Kudlik, Kornélia Szebényi, Nóra Kucsma, Bálint Szeder, Ádám Póti, Ferenc Uher, György Várady, Dávid Szüts, József Tóvári, András Füredi, and Gergely Szakács. 2020. "Establishment and Characterization of a Brca1−/−, p53−/− Mouse Mammary Tumor Cell Line" International Journal of Molecular Sciences 21, no. 4: 1185. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041185

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