Parallel Evolution under Chemotherapy Pressure in 29 Breast Cancer Cell Lines Results in Dissimilar Mechanisms of Resistance

Publication: Research - peer-reviewJournal article – Annual report year: 2012

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  • Author: Tegze, Balint

    Semmelweis University, Hungary

  • Author: Szallasi, Zoltan Imre

    Department of Systems Biology, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Haltrich, Iren

    Semmelweis University, Hungary

  • Author: Penzvalto, Zsofia

    Semmelweis University, Hungary

  • Author: Toth, Zsuzsa

    Semmelweis University, Hungary

  • Author: Liko, Istvan

    Gedeon Richter Plc, Budapest, Hungary

  • Author: Gyoerffy, Balazs

    Charité-Universitätsmedizin Berlin, Germany

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Background: Developing chemotherapy resistant cell lines can help to identify markers of resistance. Instead of using a panel of highly heterogeneous cell lines, we assumed that truly robust and convergent pattern of resistance can be identified in multiple parallel engineered derivatives of only a few parental cell lines. Methods: Parallel cell populations were initiated for two breast cancer cell lines (MDA-MB-231 and MCF-7) and these were treated independently for 18 months with doxorubicin or paclitaxel. IC50 values against 4 chemotherapy agents were determined to measure cross-resistance. Chromosomal instability and karyotypic changes were determined by cytogenetics. TaqMan RT-PCR measurements were performed for resistance-candidate genes. Pgp activity was measured by FACS. Results: All together 16 doxorubicin-and 13 paclitaxel-treated cell lines were developed showing 2-46 fold and 3-28 fold increase in resistance, respectively. The RT-PCR and FACS analyses confirmed changes in tubulin isofom composition, TOP2A and MVP expression and activity of transport pumps (ABCB1, ABCG2). Cytogenetics showed less chromosomes but more structural aberrations in the resistant cells. Conclusion: We surpassed previous studies by parallel developing a massive number of cell lines to investigate chemoresistance. While the heterogeneity caused evolution of multiple resistant clones with different resistance characteristics, the activation of only a few mechanisms were sufficient in one cell line to achieve resistance.
Original languageEnglish
JournalP L o S One
Publication date2012
Volume7
Issue2
Pagese30804
ISSN1932-6203
DOIs
StatePublished

Bibliographical note

This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial License 2.5, which permits unrestricted use, distribution, and reproduction in any noncommercial medium, provided the original work is properly cited.

CitationsWeb of Science® Times Cited: 5

Keywords

  • BIOLOGY, TOPOISOMERASE-II ACTIVITY, MULTIDRUG-RESISTANCE, LUNG-CANCER, PACLITAXEL RESISTANCE, PREDICTS RESISTANCE, ACQUIRED-RESISTANCE, EXPRESSION, PROTEIN, AMPLIFICATION, DOXORUBICIN
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