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Breast Cancer Research

, 19:65

First Online: 05 June 2017Received: 13 January 2017Accepted: 09 May 2017DOI: 10.1186-s13058-017-0855-0

Cite this article as: Smith, S.E., Mellor, P., Ward, A.K. et al. Breast Cancer Res 2017 19: 65. doi:10.1186-s13058-017-0855-0

Abstract

BackgroundBreast cancer cell lines are frequently used as model systems to study the cellular properties and biology of breast cancer. Our objective was to characterize a large, commonly employed panel of breast cancer cell lines obtained from the American Type Culture Collection ATCC 30-4500 K to enable researchers to make more informed decisions in selecting cell lines for specific studies. Information about these cell lines was obtained from a wide variety of sources. In addition, new information about cellular pathways that are activated within each cell line was generated.

MethodsWe determined key protein expression data using immunoblot analyses. In addition, two analyses on serum-starved cells were carried out to identify cellular proteins and pathways that are activated in these cells. These analyses were performed using a commercial PathScan array and a novel and more extensive phosphopeptide-based kinome analysis that queries 1290 phosphorylation events in major signaling pathways. Data about this panel of breast cancer cell lines was also accessed from several online sources, compiled and summarized for the following areas: molecular classification, mRNA expression, mutational status of key proteins and other possible cancer-associated mutations, and the tumorigenic and metastatic capacity in mouse xenograft models of breast cancer.

ResultsThe cell lines that were characterized included 10 estrogen receptor ER-positive, 12 human epidermal growth factor receptor 2 HER2-amplified and 18 triple negative breast cancer cell lines, in addition to 4 non-tumorigenic breast cell lines. Within each subtype, there was significant genetic heterogeneity that could impact both the selection of model cell lines and the interpretation of the results obtained. To capture the net activation of key signaling pathways as a result of these mutational combinations, profiled pathway activation status was examined. This provided further clarity for which cell lines were particularly deregulated in common or unique ways.

ConclusionsThese two new kinase or -Kin-OMIC- analyses add another dimension of important data about these frequently used breast cancer cell lines. This will assist researchers in selecting the most appropriate cell lines to use for breast cancer studies and provide context for the interpretation of the emerging results.

KeywordsBreast cancer cell lines Signaling pathway activation Tumorigenic Metastatic Mutations Protein expression AbbreviationsATCCAmerican Type Culture Collection

CCLECancer Cell Line Encyclopedia

COSMICCatalogue of Somatic Mutations in Cancer

CREB3L1cAMP responsive element binding protein 3-like 1

EGFREpidermal growth factor receptor

EphA-BEphrin A-B

EREstrogen receptor

FBSFetal bovine serum

FGFRFibroblast growth factor receptor

GAPDHGlyceraldehyde-3-phosphate dehydrogenase

HER2Human epidermal growth factor receptor 2

PI3KPhosphatidylinositol 3-kinase

PRProgesterone receptor

PTENPhosphatase and tensin homolog

RMARobust multi-array average

Tie2Tyrosine kinase with immunoglobulin-like and EGF-like domains 2

TNBCTriple negative breast cancer

VEGFRVascular endothelial growth factor receptor

Electronic supplementary materialThe online version of this article doi:10.1186-s13058-017-0855-0 contains supplementary material, which is available to authorized users.





Author: Shari E. Smith - Paul Mellor - Alison K. Ward - Stephanie Kendall - Megan McDonald - Frederick S. Vizeacoumar - Franco J

Source: https://link.springer.com/



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