{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:43:27Z","timestamp":1792799007430,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,1,6]],"date-time":"2017-01-06T00:00:00Z","timestamp":1483660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:p>The aim of our study was to examine the relationship between tumour IKK\u03b1 expression and breast cancer recurrence and survival. Immunohistochemistry was employed in a discovery and a validation tissue microarray to assess the association of tumour IKK\u03b1 expression and clinico\u2010pathological characteristics. After siRNA\u2010mediated silencing of IKK\u03b1, cell viability and apoptosis were assessed in MCF7 and MDA\u2010MB\u2010231 breast cancer cells. In both the discovery and validation cohorts, associations observed between IKK\u03b1 and clinical outcome measures were potentiated in oestrogen receptor (ER) positive Luminal A tumours. In the discovery cohort, cytoplasmic IKK\u03b1 was associated with disease\u2010free survival (<jats:italic>p<\/jats:italic>\u2009=\u20090.029) and recurrence\u2010free survival on tamoxifen (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) in Luminal A tumours. Nuclear IKK\u03b1 and a combination of cytoplasmic and nuclear IKK\u03b1 (total tumour cell IKK\u03b1) were associated with cancer\u2010specific survival (<jats:italic>p<\/jats:italic>\u2009=\u20090.012 and <jats:italic>p<\/jats:italic>\u2009=\u20090.007, respectively) and recurrence\u2010free survival on tamoxifen (<jats:italic>p<\/jats:italic>\u2009=\u20090.013 and <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, respectively) in Luminal A tumours. In the validation cohort, cytoplasmic IKK\u03b1 was associated with cancer\u2010specific survival (<jats:italic>p<\/jats:italic>\u2009=\u20090.023), disease\u2010free survival (<jats:italic>p<\/jats:italic>\u2009=\u20090.002) and recurrence\u2010free survival on tamoxifen (<jats:italic>p<\/jats:italic>\u2009=\u20090.009) in Luminal A tumours. Parallel experiment with breast cancer cells <jats:italic>in vitro<\/jats:italic> demonstrated the non\u2010canonical NF\u2010\u03baB pathway was inducible by exposure to lymphotoxin in ER\u2010positive MCF7 cells and not in ER\u2010negative MDA\u2010MB\u2010231 cells. Reduction in IKK\u03b1 expression by siRNA transfection increased levels of apoptosis and reduced cell viability in MCF7 but not in MDA\u2010MB\u2010231 cells. IKK\u03b1 is an important determinant of poor outcome in patients with ER\u2010positive invasive ductal breast cancer and thus may represent a potential therapeutic target.<\/jats:p>","DOI":"10.1002\/ijc.30578","type":"journal-article","created":{"date-parts":[[2016,12,24]],"date-time":"2016-12-24T14:18:27Z","timestamp":1482589107000},"page":"1633-1644","source":"Crossref","is-referenced-by-count":23,"title":["High IKK\u03b1 expression is associated with reduced time to recurrence and cancer specific survival in oestrogen receptor (ER)\u2010positive breast cancer"],"prefix":"10.1002","volume":"140","author":[{"given":"Lindsay","family":"Bennett","sequence":"first","affiliation":[{"name":"Wolfson Wohl Cancer Research Centre Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow Scotland United 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