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Research ArticleExperimental Studies

Subtypes of Triple-negative Breast Cancer Cell Lines React Differently to Eribulin Mesylate

KAREN BRÄUTIGAM, KATHARINA MITZLAFF, LISA UEBEL, FRANK KÖSTER, STEPHAN POLACK, MASCHA PERVAN, GUNNAR STEINERT, ACHIM RODY and CORNELIA LIEDTKE
Anticancer Research June 2016, 36 (6) 2759-2766;
KAREN BRÄUTIGAM
1Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Lübeck, Germany
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  • For correspondence: Karen.Braeutigam{at}uksh.de
KATHARINA MITZLAFF
1Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Lübeck, Germany
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LISA UEBEL
1Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Lübeck, Germany
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FRANK KÖSTER
1Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Lübeck, Germany
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STEPHAN POLACK
1Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Lübeck, Germany
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MASCHA PERVAN
1Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Lübeck, Germany
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GUNNAR STEINERT
2Eisai GmbH, Frankfurt am Main, Germany
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ACHIM RODY
1Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Lübeck, Germany
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CORNELIA LIEDTKE
1Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Lübeck, Germany
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    Figure 1.

    Determination of the half-maximum inhibitory concentration (IC50) of eribulin in 12 triple-negative breast cancer (TNBC) and five non-TNBC cell lines. a: Boxplot of the log IC50 concentration of eribulin for each cell line, with 95% confidence interval (CI). b: Comparison of the IC50 of TNBC vs. non-TNBC. c: Comparison of the IC50 among each subtype of TNBC. BL1: basal-like 1, BL2: basal-like 2, IM: immunomodulatory, M: mesenchymal, MSL: mesenchymal stem-like, LAR: luminal androgen receptor, U: unclassified.

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    Figure 2.

    Induction of apoptosis by eribulin treatment. a: Fluorescence-activated cell sorting (FACS) analysis in MDA-MB-468 triple-negative breast cancer (TNBC) and MCF-7 (non-TNBC) indicated increased apoptosis [early (Q2) and late (Q3)] after treatment with 10× the half-maximum inhibitory concentration (IC50) of eribulin for 24 h. b: Poly (ADP-ribose) polymerase (PARP) cleavage in western blot analyses in TNBC cell lines validated apoptosis induction by eribulin (Eri) (IC50 for 24 h), Con: Untreated, CAM: camptothecin treated (positive control).

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    Figure 3.

    Decrease of migration and invasion after eribulin treatment. a: A vertical scratch crossing the green line indicates the cell-free area. Cells migrating into the area were observed after 24 h. b: Invasion assays were performed with MDA-MB-231 cells seeded on Matrigel-coated Transwells in 24 well plates. After 24 h incubation, untreated cells and cells treated with the half-maximum inhibitory concentration (IC50) of eribulin that had migrated to bottom surfaces of the membranes were visualized by staining with Giemsa solution.

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    Figure 4.

    Gene expression changes after treatment with eribulin. The expression of gamma-aminobutyric acid type A receptor pi subunit (GABRP) (a) and (E74-like ETS transcription factor 5) ELF5 (b) after treatment with eribulin at the half-maximum inhibitory concentration (IC50) for 24 h compared to untreated controls in cell lines representing all triple-negative breast cancer (TNBC) subtypes and non-TNBC. c: The expression of tumor-related genes after eribulin treatment in four cell lines representing the TNBC subtypes basal-like 1 (BL1) (MDA-MB-468), BL2 (HDQ-P1), immunomodulatory (IM) (DU-4475) and mesenchymal stem-like (MSL) (MDA-MB-231). Expression ratios are shown as 2-log scale values. LAR: Luminal androgen receptor, U: unclassified. *Significantly different from the control at p<0.05.

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Vol. 36, Issue 6
June 2016
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Subtypes of Triple-negative Breast Cancer Cell Lines React Differently to Eribulin Mesylate
KAREN BRÄUTIGAM, KATHARINA MITZLAFF, LISA UEBEL, FRANK KÖSTER, STEPHAN POLACK, MASCHA PERVAN, GUNNAR STEINERT, ACHIM RODY, CORNELIA LIEDTKE
Anticancer Research Jun 2016, 36 (6) 2759-2766;

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Subtypes of Triple-negative Breast Cancer Cell Lines React Differently to Eribulin Mesylate
KAREN BRÄUTIGAM, KATHARINA MITZLAFF, LISA UEBEL, FRANK KÖSTER, STEPHAN POLACK, MASCHA PERVAN, GUNNAR STEINERT, ACHIM RODY, CORNELIA LIEDTKE
Anticancer Research Jun 2016, 36 (6) 2759-2766;
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Keywords

  • Triple-negative breast cancer
  • TNBC
  • subtypes
  • eribulin
  • cell lines
  • chemosensitivity
  • proliferation
  • apoptosis
  • migration
  • invasion
  • gene expression
  • malignant transformation
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