Radiation-Induced Reprogramming of Breast Cancer Cells§

Authors

  • Chann Lagadec,

    1. Department of Radiation Oncology, David Geffen School of MedicineUniversity of California Los Angeles, Los Angeles, California, USA
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  • Erina Vlashi,

    1. Department of Radiation Oncology, David Geffen School of MedicineUniversity of California Los Angeles, Los Angeles, California, USA
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  • Lorenza Della Donna,

    1. Department of Radiation Oncology, David Geffen School of MedicineUniversity of California Los Angeles, Los Angeles, California, USA
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  • Carmen Dekmezian,

    1. Department of Radiation Oncology, David Geffen School of MedicineUniversity of California Los Angeles, Los Angeles, California, USA
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  • Frank Pajonk

    Corresponding author
    1. Department of Radiation Oncology, David Geffen School of MedicineUniversity of California Los Angeles, Los Angeles, California, USA
    2. Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, USA
    • Department of Radiation Oncology, David Geffen School of Medicine, UCLA, 10833 Le Conte Ave, Los Angeles, California 90095-1714, USA
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    • Telephone: +1-310-206-8733; Fax: +1-310-206-1260


  • Author contributions: C.L.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; E.V.: conception and design and data analysis and interpretation; L.D.D.: conception and design; C.D.: collection and assembly of data; F.P.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript, and financial support.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS February 10, 2012.

Abstract

Breast cancers are thought to be organized hierarchically with a small number of breast cancer stem cells (BCSCs) able to regrow a tumor while their progeny lack this ability. Recently, several groups reported enrichment for BCSCs when breast cancers were subjected to classic anticancer treatment. However, the underlying mechanisms leading to this enrichment are incompletely understood. Using non-BCSCs sorted from patient samples, we found that ionizing radiation reprogrammed differentiated breast cancer cells into induced BCSCs (iBCSCs). iBCSCs showed increased mammosphere formation, increased tumorigenicity, and expressed the same stemness-related genes as BCSCs from nonirradiated samples. Reprogramming occurred in a polyploid subpopulation of cells, coincided with re-expression of the transcription factors Oct4, sex determining region Y-box 2, Nanog, and Klf4, and could be partially prevented by Notch inhibition. We conclude that radiation may induce a BCSC phenotype in differentiated breast cancer cells and that this mechanism contributes to increased BCSC numbers seen after classic anticancer treatment. STEM CELLS 2012;30:833–844

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