SIRT2: Tumour suppressor or tumour promoter in operable breast cancer?

McGlynn, L.M. et al. (2014) SIRT2: Tumour suppressor or tumour promoter in operable breast cancer? European Journal of Cancer, 50(2), pp. 290-301. (doi:10.1016/j.ejca.2013.10.005) (PMID:24183459)

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Abstract

Purpose Sirtuins comprise a family of genes involved in cellular stress, survival and damage responses. They have been implicated in a range of diseases including cancer, with most information pertaining to their function in tumourigenesis being derived from in vitro studies, or model organisms. Their putative roles as tumour suppressors or tumour promoters remain to be validated in vivo. Little is known about their role in breast tumourigenesis. We sought to evaluate the seven sirtuin family members (SIRT1–7) in a human breast cancer cohort, in relation to clinico-pathological features and outcome of the disease.<p></p> Materials and methods Immunohistochemical analysis of SIRT1–7 protein levels was undertaken in 392 oestrogen receptor (ER+ve) and 153 ER−ve breast tumour samples. SIRT1–7 transcriptional levels were assessed in normal (n = 25), non-malignant (n = 73) and malignant (n = 70) breast tissue using Relative Quantitative Real Time PCR. Statistical analyses determined if SIRT1–7 transcription or protein expression was associated with clinical parameters or outcome.<p></p> Results In ER−ve tumours, high protein levels of nuclear SIRT2 were associated with reduced time to recurrence and disease-specific death. This association was only observed in Grade 3 tumours. In the ER+ve cohort, high SIRT2 nuclear levels were associated with shorter disease-free survival and time to recurrence whilst on Tamoxifen, in patients with Grade 3 tumours. Conversely, in Grade 2 tumours, high SIRT2 levels were associated with increased time to recurrence.<p></p> Conclusions Our data suggest that SIRT2 is the sirtuin predominantly involved in breast tumourigenesis and prognosis. It indicates that SIRT2 acts as a tumour suppressor or tumour promoter dependent upon breast tumour grade.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Payne, Professor Anthony and Reilly, Miss Justice and McMillan, Professor Donald and Shiels, Professor Paul and Mallon, Dr Elizabeth and Mohammed, Miss Zahra and McGlynn, Dr Liane and Edwards, Dr Joanne and MacDonald, Dr Alasdair and Zino, Mr Samer
Authors: McGlynn, L.M., Zino, S., MacDonald, A.I., Curle, J., Reilly, J.E., Mohammed, Z.M.A., McMillan, D.C., Mallon, E., Payne, A.P., Edwards, J., and Shiels, P.G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:European Journal of Cancer
Publisher:Elsevier
ISSN:0959-8049
ISSN (Online):1879-0852

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