Evidence map›Paper›PMID 30987655›Full record

ArticleRadiation oncology (London, England)2019

Development and characterisation of acquired radioresistant breast cancer cell lines.

Mark Gray, Arran K Turnbull, Carol Ward, James Meehan, Carlos Martínez-Pérez, Maria Bonello, Lisa Y Pang, Simon P Langdon, Ian H Kunkler, Alan Murray and 1 more

Abstract read
In one paragraph

Article in Radiation oncology (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  6. Article
  7. Role of Different Enzymes in HInternational journal of molecular sciences · 2025
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  17. Neoadjuvant radiotherapy in ERFrontiers in immunology · 2024
    Article
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1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Mark GrayThe Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Edinburgh, Scotland. s9900757@sms.ed.ac.uk.ORCID http://orcid.org/0000-0003-2035-1425
Arran K TurnbullCancer Research UK Edinburgh Centre and Division of Pathology Laboratories, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, Scotland.
Carol WardThe Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Edinburgh, Scotland.
James MeehanCancer Research UK Edinburgh Centre and Division of Pathology Laboratories, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, Scotland.
Carlos Martínez-PérezCancer Research UK Edinburgh Centre and Division of Pathology Laboratories, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, Scotland.
Maria BonelloCancer Research UK Edinburgh Centre and Division of Pathology Laboratories, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, Scotland.
Lisa Y PangThe Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Edinburgh, Scotland.
Simon P LangdonCancer Research UK Edinburgh Centre and Division of Pathology Laboratories, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, Scotland.
Ian H KunklerCancer Research UK Edinburgh Centre and Division of Pathology Laboratories, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, Scotland.
Alan MurraySchool of Engineering, Faraday Building, The King's Buildings, University of Edinburgh, Edinburgh, Scotland.
David ArgyleThe Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Edinburgh, Scotland.

Funding

Engineering and Physical Sciences Research Council EP/K-34510/1
6 · The paper itself

Abstract

backgroundRadiotherapy plays an important role in the multimodal treatment of breast cancer. The response of a breast tumour to radiation depends not only on its innate radiosensitivity but also on tumour repopulation by cells that have developed radioresistance. Development of effective cancer treatments will require further molecular dissection of the processes that contribute to resistance.

methodsRadioresistant cell lines were established by exposing MDA-MB-231, MCF-7 and ZR-751 parental cells to increasing weekly doses of radiation. The development of radioresistance was evaluated through proliferation and colony formation assays. Phenotypic characterisation included migration and invasion assays and immunohistochemistry. Transcriptomic data were also generated for preliminary hypothesis generation involving pathway-focused analyses.

resultsProliferation and colony formation assays confirmed radioresistance. Radioresistant cells exhibited enhanced migration and invasion, with evidence of epithelial-to-mesenchymal-transition. Significantly, acquisition of radioresistance in MCF-7 and ZR-751 cell lines resulted in a loss of expression of both ERα and PgR and an increase in EGFR expression; based on transcriptomic data they changed subtype classification from their parental luminal A to HER2-overexpressing (MCF-7 RR) and normal-like (ZR-751 RR) subtypes, indicating the extent of phenotypic changes and cellular plasticity involved in this process. Radioresistant cell lines derived from ER+ cells also showed a shift from ER to EGFR signalling pathways with increased MAPK and PI3K activity.

conclusionsThis is the first study to date that extensively describes the development and characterisation of three novel radioresistant breast cancer cell lines through both genetic and phenotypic analysis. More changes were identified between parental cells and their radioresistant derivatives in the ER+ (MCF-7 and ZR-751) compared with the ER- cell line (MDA-MB-231) model; however, multiple and likely interrelated mechanisms were identified that may contribute to the development of acquired resistance to radiotherapy.

Indexed as

Gamma RaysRadiation ToleranceApoptosisBiomarkers, TumorBreast NeoplasmsCell MovementCell ProliferationFemaleGene Expression ProfilingHumansNeoplasm InvasivenessRadiation-Sensitizing AgentsSignal TransductionSulfonamidesTumor Cells, CulturedBiomarkers, TumorRadiation-Sensitizing AgentsSulfonamidesBreast cancerCharacterisation of radioresistant cell linesER and EGFR signallingGlobal gene analysisRadioresistance

Identifiers

PMID30987655
PMCPMC6466735

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.