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New generation breast cancer cell lines developed from patient-derived xenografts.
Finlay-Schultz, Jessica; Jacobsen, Britta M; Riley, Duncan; Paul, Kiran V; Turner, Scott; Ferreira-Gonzalez, Andrea; Harrell, J Chuck; Kabos, Peter; Sartorius, Carol A.
Afiliação
  • Finlay-Schultz J; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
  • Jacobsen BM; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
  • Riley D; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
  • Paul KV; Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
  • Turner S; Department of Pathology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
  • Ferreira-Gonzalez A; Department of Pathology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
  • Harrell JC; Department of Pathology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
  • Kabos P; Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. Peter.Kabos@cuanschutz.edu.
  • Sartorius CA; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. Carol.Sartorius@cuanschutz.edu.
Breast Cancer Res ; 22(1): 68, 2020 06 23.
Article em En | MEDLINE | ID: mdl-32576280
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Carcinoma Lobular / Carcinoma Ductal de Mama / Linhagem Celular Tumoral Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Breast Cancer Res Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Carcinoma Lobular / Carcinoma Ductal de Mama / Linhagem Celular Tumoral Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Breast Cancer Res Ano de publicação: 2020 Tipo de documento: Article