TY - JOUR
T1 - Establishment and Characterization of a Brca1−/−, p53−/− Mouse Mammary Tumor Cell Line
AU - Hámori, Lilla
AU - Kudlik, Gyöngyi
AU - Szebényi, Kornélia
AU - Kucsma, Nóra
AU - Szeder, Bálint
AU - Póti, Ádám
AU - Uher, Ferenc
AU - Várady, György
AU - Szüts, Dávid
AU - Tóvári, József
AU - Füredi, András
AU - Szakács, Gergely
N1 - Funding: This research was funded by the National Research, Development and Innovation Fund of Hungary (2019‐1.3.1‐KK‐2019‐00007 to G.S. and A.F., K_124881 to D.S., and K116295 to J.T.) and a Momentum Grant from the Hungarian Academy of Sciences (G.S.). Financial support from the 2019 Thematic Excellence Program (TUDFO/51757/2019‐ITM) is also acknowledged.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/2/11
Y1 - 2020/2/11
N2 - 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.
AB - 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.
KW - BRCA1
KW - Breast cancer
KW - Cancer cell line
KW - Genetically engineered mouse model
UR - http://www.scopus.com/inward/record.url?scp=85079337505&partnerID=8YFLogxK
U2 - 10.3390/ijms21041185
DO - 10.3390/ijms21041185
M3 - Article
C2 - 32053991
AN - SCOPUS:85079337505
SN - 1661-6596
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 4
M1 - 1185
ER -