Breast cancer stem cell-like cells are more sensitive to ionizing radiation than non-stem cells: role of ATM

Seog-Young Kim; Juong G Rhee; Xinxin Song; Edward V Prochownik; Douglas R Spitz; Yong J Lee

doi:10.1371/journal.pone.0050423

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Breast cancer stem cell-like cells are more sensitive to ionizing radiation than non-stem cells: role of ATM

Journal article

Open access

Peer reviewed

Breast cancer stem cell-like cells are more sensitive to ionizing radiation than non-stem cells: role of ATM

Seog-Young Kim, Juong G Rhee, Xinxin Song, Edward V Prochownik, Douglas R Spitz and Yong J Lee

PloS one, Vol.7(11), pp.e50423-e50423

2012

DOI: 10.1371/journal.pone.0050423

PMCID: PMC3503893

PMID: 23185620

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Abstract

There are contradictory observations about the different radiosensitivities of cancer stem cells and cancer non-stem cells. To resolve these contradictory observations, we studied radiosensitivities by employing breast cancer stem cell (CSC)-like MDA-MB231 and MDA-MB453 cells as well as their corresponding non-stem cells. CSC-like cells proliferate without differentiating and have characteristics of tumor-initiating cells [1]. These cells were exposed to γ-rays (1.25-8.75 Gy) and survival curves were determined by colony formation. A final slope, D(0), of the survival curve for each cell line was determined to measure radiosensitivity. The D(0) of CSC-like and non-stem MDA-MB-453 cells were 1.16 Gy and 1.55 Gy, respectively. Similar results were observed in MDA-MB-231 cells (0.94 Gy vs. 1.56 Gy). After determination of radiosensitivity, we investigated intrinsic cellular determinants which influence radiosensitivity including cell cycle distribution, free-radical scavengers and DNA repair. We observed that even though cell cycle status and antioxidant content may contribute to differential radiosensitivity, differential DNA repair capacity may be a greater determinant of radiosensitivity. Unlike non-stem cells, CSC-like cells have little/no sublethal damage repair, a low intracellular level of ataxia telangiectasia mutated (ATM) and delay of γ-H2AX foci removal (DNA strand break repair). These results suggest that low DNA repair capacity is responsible for the high radiosensitivity of these CSC-like cells.

Gamma Rays

Humans

DNA Repair - radiation effects

DNA Repair - genetics

Breast Neoplasms - metabolism

DNA-Binding Proteins - metabolism

Neoplastic Stem Cells - metabolism

DNA Fragmentation

Tumor Suppressor Proteins - genetics

Cell Cycle Proteins - genetics

Neoplastic Stem Cells - pathology

Female

Tumor Cells, Cultured

Protein-Serine-Threonine Kinases - metabolism

Neoplastic Stem Cells - radiation effects

Tumor Suppressor Proteins - metabolism

Free Radical Scavengers - metabolism

Cell Cycle - radiation effects

Cell Cycle Proteins - metabolism

Protein-Serine-Threonine Kinases - genetics

Radiation Tolerance - genetics

Ataxia Telangiectasia Mutated Proteins

DNA-Binding Proteins - genetics

Mice, SCID

Organ Specificity

Cell Survival - radiation effects

Xenograft Model Antitumor Assays

Animals

Breast Neoplasms - genetics

Histones - genetics

Breast Neoplasms - pathology

Gene Expression Regulation, Neoplastic - radiation effects

Mice

Histones - metabolism

Cell Proliferation - radiation effects

Details

Title: Subtitle: Breast cancer stem cell-like cells are more sensitive to ionizing radiation than non-stem cells: role of ATM
Creators: Seog-Young Kim - Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Juong G Rhee
Xinxin Song
Edward V Prochownik
Douglas R Spitz
Yong J Lee
Resource Type: Journal article
Publication Details: PloS one, Vol.7(11), pp.e50423-e50423
DOI: 10.1371/journal.pone.0050423
PMID: 23185620
PMCID: PMC3503893
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: BC103217 / NCI NIH HHS R01 CA123484 / NCI NIH HHS R01 CA116430 / NCI NIH HHS R01 CA094858 / NCI NIH HHS NIH R01CA133114 / NCI NIH HHS NIH P30 CA086862 / NCI NIH HHS R01 CA121904 / NCI NIH HHS R01 CA133114 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA100045 / NCI NIH HHS R01 CA140554 / NCI NIH HHS
Language: English
Date published: 2012
Academic Unit: Pathology; Radiation Oncology
Record Identifier: 9984047864802771

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