Nouf Al-Subhi
Targeting ataxia telangiectasia mutated and Rad3 related kinase (ATR) in PTEN deficient breast cancers for personalized therapy
Al-Subhi, Nouf; Ali, Reem; Abdel-Fatah, Tarek; Moseley, Paul M.; Chan, Stephen Y.T.; Green, Andrew R.; Ellis, Ian O.; Rakha, Emad; Madhusudan, Srinivasan
Authors
Reem Ali
Tarek Abdel-Fatah
Paul M. Moseley
Stephen Y.T. Chan
ANDREW GREEN ANDREW.GREEN@NOTTINGHAM.AC.UK
Associate Professor
Professor IAN ELLIS IAN.ELLIS@NOTTINGHAM.AC.UK
Professor of Cancer Pathology
EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology
SRINIVASAN MADHUSUDAN srinivasan.madhusudan@nottingham.ac.uk
Professor of Medical Oncology
Abstract
Purpose: PTEN, a negative regulator of PI3K signaling, is involved in DNA repair. ATR is a key sensor of DNA damage and replication stress. We evaluated whether ATR signaling has clinical significance and could be targeted by synthetic lethality in PTEN deficient triple negative breast cancer (TNBC).
Methods: PTEN, ATR and pCHK1Ser345 protein level was evaluated in 1650 human breast cancers. ATR blockade by VE-821 was investigated in PTEN-proficient (MDAMB-231) and PTEN-deficient (BT-549, MDA-MB-468) TNBC cell lines. Functional studies included DNA repair expression profiling, MTS cell-proliferation assay, FACS (cell cycle progression & ?H2AX accumulation) and FITC-annexin V flow cytometry analysis.
Results: Low nuclear PTEN was associated with higher grade, pleomorphism, dedifferentiation, higher mitotic index, larger tumour size, ER negativity, and shorter survival (p values
Citation
Al-Subhi, N., Ali, R., Abdel-Fatah, T., Moseley, P. M., Chan, S. Y., Green, A. R., …Madhusudan, S. (2018). Targeting ataxia telangiectasia mutated and Rad3 related kinase (ATR) in PTEN deficient breast cancers for personalized therapy. Breast Cancer Research and Treatment, 169(2), 277–286. https://doi.org/10.1007/s10549-018-4683-4
Journal Article Type | Article |
---|---|
Acceptance Date | Jan 18, 2018 |
Online Publication Date | Feb 2, 2018 |
Publication Date | 2018-06 |
Deposit Date | Jan 23, 2018 |
Publicly Available Date | Feb 2, 2018 |
Journal | Breast Cancer Research and Treatment |
Print ISSN | 0167-6806 |
Electronic ISSN | 1573-7217 |
Publisher | Springer Verlag |
Peer Reviewed | Peer Reviewed |
Volume | 169 |
Issue | 2 |
Pages | 277–286 |
DOI | https://doi.org/10.1007/s10549-018-4683-4 |
Keywords | Breast cancer; biomarker; PTEN; ATR; Triple negative breast cancer; Synthetic lethality |
Public URL | https://nottingham-repository.worktribe.com/output/908295 |
Publisher URL | https://link.springer.com/article/10.1007%2Fs10549-018-4683-4 |
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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