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

Bennett, Lindsay and Quinn, Jean and McCall, Pamela and Mallon, Elizabeth A. and Horgan, Paul G. and McMillan, Donald C. and Paul, Andrew and Edwards, Joanne (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. ISSN 0020-7136 (https://doi.org/10.1002/ijc.30578)

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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.

ORCID iDs

Bennett, Lindsay, Quinn, Jean, McCall, Pamela, Mallon, Elizabeth A., Horgan, Paul G., McMillan, Donald C., Paul, Andrew ORCID logoORCID: https://orcid.org/0000-0001-5775-2332 and Edwards, Joanne;
  • Item type:Article
    ID code:59645
    Dates:
    Date
    Event
    1 April 2017
    Published
    22 December 2016
    Published Online
    9 December 2016
    Accepted
    Notes:This is the peer reviewed version of the following article: Bennett, L., Quinn, J., McCall, P., Mallon, E. A., Horgan, P. G., McMillan, D. C., ... Edwards, J. (2016). 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, which has been published in final form at https://dx.doi.org/10.1002/ijc.30578. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
    Keywords:breast cancer, oestrogen receptor, IKKα, non canonical NF-kB pathway, recurrence on tamoxifen, tumour markers, endocrine treated breast cancer, Neoplasms. Tumors. Oncology (including Cancer), Oncology
    Subjects:Medicine > Internal medicine > Neoplasms. Tumors. Oncology (including Cancer)
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:30 Jan 2017 15:45
    Last modified:04 Dec 2022 04:02
    URI:https://strathprints.strath.ac.uk/id/eprint/59645
CORE (COnnecting REpositories)