New generation breast cancer cell lines developed from patient-derived xenografts
| العنوان: | New generation breast cancer cell lines developed from patient-derived xenografts |
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| المؤلفون: | Andrea Ferreira-Gonzalez, Jessica Finlay-Schultz, J. Chuck Harrell, Kiran V. Paul, Scott A. Turner, Duncan Riley, Peter Kabos, Carol A. Sartorius, Britta M. Jacobsen |
| المصدر: | Breast Cancer Research : BCR Breast Cancer Research, Vol 22, Iss 1, Pp 1-12 (2020) |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Receptor, ErbB-2, Breast cancer subtypes, Cell, Cell Culture Techniques, Estrogen receptor, Breast Neoplasms, Mice, SCID, Biology, Oncogenomics, lcsh:RC254-282, Mice, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, Cyclin D1, Mice, Inbred NOD, Cell Line, Tumor, medicine, Animals, Humans, skin and connective tissue diseases, 030304 developmental biology, 0303 health sciences, Fulvestrant, Gene Expression Profiling, Carcinoma, Ductal, Breast, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Breast cancer cell lines, Carcinoma, Lobular, Patient-derived xenografts, medicine.anatomical_structure, Receptors, Estrogen, 030220 oncology & carcinogenesis, Cancer research, Heterografts, Female, Receptors, Progesterone, Estrogen receptor alpha, Tamoxifen, Research Article, medicine.drug |
| الوصف: | Background Breast cancer is a highly heterogeneous disease characterized by multiple histologic and molecular subtypes. While a myriad of breast cancer cell lines have been developed over the past 60 years, estrogen receptor alpha (ER)+ disease and some mutations associated with this subtype remain underrepresented. Here we describe six breast cancer cell lines derived from patient-derived xenografts (PDX) and their general characteristics. Methods Established breast cancer PDX were processed into cell suspensions and placed into standard 2D cell culture; six emerged into long-term passageable cell lines. Cell lines were assessed for protein expression of common luminal, basal, and mesenchymal markers, growth assessed in response to estrogens and endocrine therapies, and RNA-seq and oncogenomics testing performed to compare relative transcript levels and identify putative oncogenic drivers. Results Three cell lines express ER and two are also progesterone receptor (PR) positive; PAM50 subtyping identified one line as luminal A. One of the ER+PR+ lines harbors a D538G mutation in the gene for ER (ESR1), providing a natural model that contains this endocrine-resistant genotype. The third ER+PR−/low cell line has mucinous features, a rare histologic type of breast cancer. The three other lines are ER− and represent two basal-like and a mixed ductal/lobular breast cancer. The cell lines show varied responses to tamoxifen and fulvestrant, and three were demonstrated to regrow tumors in vivo. RNA sequencing confirms all cell lines are human and epithelial. Targeted oncogenomics testing confirmed the noted ESR1 mutation in addition to other mutations (i.e., PIK3CA, BRCA2, CCND1, NF1, TP53, MYC) and amplifications (i.e., FGFR1, FGFR3) frequently found in breast cancers. Conclusions These new generation breast cancer cell lines add to the existing repository of breast cancer models, increase the number of ER+ lines, and provide a resource that can be genetically modified for studying several important clinical breast cancer features. |
| تدمد: | 1465-542X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5cc683ae8901a9483abdf40532ec4ff4 https://doi.org/10.1186/s13058-020-01300-y |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5cc683ae8901a9483abdf40532ec4ff4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1465542X |
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