High IKKα expression is associated with reduced time to recurrence and cancer specific survival in oestrogen receptor (ER)-positive breast cancer

Bennett, L., Quinn, J. , McCall, P., Mallon, E. A., Horgan, P. G. , McMillan, D. C. , Paul, A. and Edwards, J. (2017) High IKKα expression is associated with reduced time to recurrence and cancer specific survival in oestrogen receptor (ER)-positive breast cancer. International Journal of Cancer, 140(7), pp. 1633-1644. (doi:10.1002/ijc.30578) (PMID:28006839)

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Abstract

The aim of our study was to examine the relationship between tumour IKKα expression and breast cancer recurrence and survival. Immunohistochemistry was employed in a discovery and a validation tissue microarray to assess the association of tumour IKKα expression and clinico-pathological characteristics. After siRNA-mediated silencing of IKKα, cell viability and apoptosis were assessed in MCF7 and MDA-MB-231 breast cancer cells. In both the discovery and validation cohorts, associations observed between IKKα and clinical outcome measures were potentiated in oestrogen receptor (ER) positive Luminal A tumours. In the discovery cohort, cytoplasmic IKKα was associated with disease-free survival (p = 0.029) and recurrence-free survival on tamoxifen (p < 0.001) in Luminal A tumours. Nuclear IKKα and a combination of cytoplasmic and nuclear IKKα (total tumour cell IKKα) were associated with cancer-specific survival (p = 0.012 and p = 0.007, respectively) and recurrence-free survival on tamoxifen (p = 0.013 and p < 0.001, respectively) in Luminal A tumours. In the validation cohort, cytoplasmic IKKα was associated with cancer-specific survival (p = 0.023), disease-free survival (p = 0.002) and recurrence-free survival on tamoxifen (p = 0.009) in Luminal A tumours. Parallel experiment with breast cancer cells in vitro demonstrated the non-canonical NF-κB pathway was inducible by exposure to lymphotoxin in ER-positive MCF7 cells and not in ER-negative MDA-MB-231 cells. Reduction in IKKα expression by siRNA transfection increased levels of apoptosis and reduced cell viability in MCF7 but not in MDA-MB-231 cells. IKKα is an important determinant of poor outcome in patients with ER-positive invasive ductal breast cancer and thus may represent a potential therapeutic target.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Horgan, Professor Paul and Mallon, Dr Elizabeth and Bennett, Miss Lindsay and Quinn, Dr Jean and Edwards, Professor Joanne and McMillan, Professor Donald and McCall, Dr Pamela
Authors: Bennett, L., Quinn, J., McCall, P., Mallon, E. A., Horgan, P. G., McMillan, D. C., Paul, A., and Edwards, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:International Journal of Cancer
Publisher:Wiley
ISSN:0020-7136
ISSN (Online):1097-0215
Published Online:06 January 2017
Copyright Holders:Copyright © 2017 Wiley
First Published:First published in International Journal of Cancer 140(7):1633–1644
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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