RECQL4 helicase has oncogenic potential in sporadic breast cancers.

Autor: Arora A; Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, UK.; Department of Oncology, Nottingham University Hospitals, UK., Agarwal D; School of Science and Technology, Nottingham Trent University, Clifton Campus, Nottingham, UK., Abdel-Fatah TM; Department of Oncology, Nottingham University Hospitals, UK., Lu H; Laboratory of Molecular Gerontology, Biomedical Research Center, National Institute on Ageing, National Institutes of Health, Baltimore, MD, USA., Croteau DL; Laboratory of Molecular Gerontology, Biomedical Research Center, National Institute on Ageing, National Institutes of Health, Baltimore, MD, USA., Moseley P; Department of Oncology, Nottingham University Hospitals, UK., Aleskandarany MA; Department of Pathology, School of Medicine, University of Nottingham, UK., Green AR; Department of Pathology, School of Medicine, University of Nottingham, UK., Ball G; School of Science and Technology, Nottingham Trent University, Clifton Campus, Nottingham, UK., Rakha EA; Department of Pathology, School of Medicine, University of Nottingham, UK., Chan SY; Department of Oncology, Nottingham University Hospitals, UK., Ellis IO; Department of Pathology, School of Medicine, University of Nottingham, UK., Wang LL; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA., Zhao Y; Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, People's Republic of China., Balajee AS; REAC/TS, Oak Ridge Associated Universities, Oak Ridge Institute for Science and Education, TN, USA., Bohr VA; Laboratory of Molecular Gerontology, Biomedical Research Center, National Institute on Ageing, National Institutes of Health, Baltimore, MD, USA., Madhusudan S; Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, UK.; Department of Oncology, Nottingham University Hospitals, UK.
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2016 Mar; Vol. 238 (4), pp. 495-501. Date of Electronic Publication: 2016 Feb 02.
DOI: 10.1002/path.4681
Abstrakt: RECQL4 helicase is a molecular motor that unwinds DNA, a process essential during DNA replication and DNA repair. Germ-line mutations in RECQL4 cause type II Rothmund-Thomson syndrome (RTS), characterized by a premature ageing phenotype and cancer predisposition. RECQL4 is widely considered to be a tumour suppressor, although its role in human breast cancer is largely unknown. As the RECQL4 gene is localized to chromosome 8q24, a site frequently amplified in sporadic breast cancers, we hypothesized that it may play an oncogenic role in breast tumourigenesis. To address this, we analysed large cohorts for gene copy number changes (n = 1977), mRNA expression (n = 1977) and protein level (n = 1902). Breast cancer incidence was also explored in 58 patients with type II RTS. DNA replication dynamics and chemosensitivity was evaluated in RECQL4-depleted breast cancer cells in vitro. Amplification or gain in gene copy number (30.6%), high-level mRNA expression (51%) and high levels of protein (23%) significantly associated with aggressive tumour behaviour, including lymph node positivity, larger tumour size, HER2 overexpression, ER-negativity, triple-negative phenotypes and poor survival. RECQL4 depletion impaired the DNA replication rate and increased chemosensitivity in cultured breast cancer cells. Thus, although recognized as a 'safe guardian of the genome', our data provide compelling evidence that RECQL4 is tumour promoting in established breast cancers. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
(Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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