Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines

Hollestelle, Antoinette; Nagel, Jord H.A.; Smid, Marcel; Lam, Suzanne; Elstrodt, Fons; Wasielewski, Marijke; Ng, Soon Seng; French, Pim J.; Peeters, Justine K.; Rozendaal, Marieke; Riaz, Muhammad Bilal; Koopman, Daphne G.; Hagen, Timo L.M. ten; Leeuw, Bertie H.C.G.M. de; Zwarthoff, Ellen C.; Teunisse, Amina F.A.S.; Spek, Peter J. van der; Klijn, Jan G.M.; Dinjens, Winand N.M.; Ethier, Stephen P.; Clevers, Hans; Jochemsen, Aart G.; Bakker, Michael A. den; Foekens, John A.; Martens, John W.M.; Schutte, Mieke

doi:10.1007/s10549-009-0460-8

Cited by 261 publications

(278 citation statements)

References 45 publications

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“…Consistent with these notions are the recent findings that mutations in BRCA1 can affect the differentiation potential of luminal progenitor cells, leading to increased basal-like differentiation in tumors (5,11). Because carcinoma cells from luminal ER + and basal-like ER − breast cancers are reported to contain distinguishing and even mutually exclusive sets of mutated or misregulated genes (25), the genetic and epigenetic alterations sustained during early stages of transformation could alter differentiation commitment programs in a common cell of origin, leading to tumors with different phenotypes. In this model, undifferentiated tumors could result when the common cell of origin lost lineage commitment potential during the acquisition of malignancy.…”

Section: Discussionmentioning

confidence: 70%

Defining the cellular precursors to human breast cancer

Keller

Arendt

Skibinski

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

194

216

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Human breast cancers are broadly classified based on their geneexpression profiles into luminal-and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM + ) and basal/myoepithelial (CD10 + ). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM + epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10 + cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10 + breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues.cell of origin | epidermal progenitor cells | luminal progenitors

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Section: Discussionmentioning

confidence: 70%

Defining the cellular precursors to human breast cancer

Keller

Arendt

Skibinski

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

194

216

View full text Add to dashboard Cite

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“…In order to identify an additional marker expressed on EpCAM-negative breast cancer cells, we used our well-defined panel of 41 human breast cancer cell lines [13,14]. The intrinsic subtype of these cell lines has been determined by gene expression profiling previously [1].…”

Section: Breast Cancer Cell Linesmentioning

confidence: 99%

“…The transcript levels of the 41 cell lines were determined with Affymetrix GeneChip Exon 1.0 ST Arrays (Affymetrix UK Ltd., Wooburn Green, UK) as described previously [14].…”

Section: Cd146 Mrna Expression Levelsmentioning

confidence: 99%

“…As previously reported, our cell line panel consists of 10 normal-like, 5 basal-like, 5 erbb2 and 21 luminal breast cancers as determined by gene expression profiling according to the intrinsic subtypes of Perou and Sorlie [1,14]. As the MDA-MB-435 normal-like cell line has been the subject of debate in literature recently with doubts about its origin [18][19][20], we excluded this cell line from our experiments.…”

Section: Breast Cancer Cell Linesmentioning

confidence: 99%

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Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146

Mostert

Kraan

Vries

et al. 2010

Breast Cancer Res Treat

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PurposeMost assays to detect circulating tumor cells (CTCs) rely on EpCAM expression on tumor cells.Recently, our group reported that in contrast to other molecular breast cancer subtypes, "normallike" cell lines lack EpCAM expression and are thus missed when CTCs are captured with EpCAM-based technology [1]. Here, the use of CD146 is introduced to detect EpCAM-negative CTCs, thereby improving CTC detection. Methods CD146and EpCAM expression were assessed in our panel of 41 breast cancer cell lines. Cells from 14 cell lines, 9 of which normal-like, were spiked into healthy donor blood. Using CellSearch™ technology, 7.5 mL whole blood was enriched for CTCs by adding ferrofluids loaded with antibodies against EpCAM and/or CD146 followed by staining for Cytokeratin and DAPI. Hematopoietic cells and circulating endothelial cells (CECs) were counterstained with CD45 and CD34, respectively. A similar approach was applied for blood samples of 20 advanced breast cancer patients. ResultsEight of 9 normal-like breast cancer cell lines lacked EpCAM expression but did express CD146.Five of these 8 could be adequately recovered by anti-CD146 ferrofluids. Of 20 advanced breast cancer patients whose CTCs were enumerated with anti-EpCAM and anti-CD146 ferrofluids, 9 had CD146+ CTCs. ConclusionsCells from breast cancer cell lines that lack EpCAM expression frequently express CD146 and can be recovered by anti-CD146 ferrofluids. CD146+ CTCs are present in the peripheral blood of breast cancer patients with advanced disease. Combined use of anti-CD146 and anti-EpCAM is likely to improve CTC detection in breast cancer patients.3

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“…Over the past decade, several groups have mapped the genotypes, phenotypes, in vitro and in vivo behaviour of cell line models in order to define their relevance to human disease, provide benchmarks for assessing the integrity of cell line stocks around the world and to help contextualise experimental data. The approaches have included exome sequencing, copy-number analysis, whole-transcriptome and targeted analysis of biomarkers relevant to breast cancer or mammary gland development [1][2][3][4][5][6][7][8][9]. These studies proposed various frameworks in which each line could be categorized.…”

Section: Introductionmentioning

confidence: 99%

Multidimensional phenotyping of breast cancer cell lines to guide preclinical research

Saunus

Smart

Kutasovic

et al. 2017

Breast Cancer Res Treat

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Purpose Cell lines are extremely useful tools in breast cancer research. Their key benefits include a high degree of control over experimental variables and reproducibility. However, the advantages must be balanced against the limitations of modelling such a complex disease in vitro. Informed selection of cell line(s) for a given experiment now requires essential knowledge about molecular and phenotypic context in the culture dish.

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Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines

Cited by 261 publications

References 45 publications

Defining the cellular precursors to human breast cancer

Defining the cellular precursors to human breast cancer

Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146

Multidimensional phenotyping of breast cancer cell lines to guide preclinical research

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