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New generation breast cancer cell lines developed from patient-derived xenografts.

Abstract：

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.

journal_name

Breast Cancer Res

journal_title

Breast cancer research : BCR

authors

Finlay-Schultz J,Jacobsen BM,Riley D,Paul KV,Turner S,Ferreira-Gonzalez A,Harrell JC,Kabos P,Sartorius CA

doi

10.1186/s13058-020-01300-y

subject

Has Abstract

pub_date

2020-06-23 00:00:00

pages

issue

eissn

1465-5411

issn

1465-542X

pii

10.1186/s13058-020-01300-y

journal_volume

pub_type

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New generation breast cancer cell lines developed from patient-derived xenografts.