Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.579557
Title: Characterisation of genes associated with tamoxifen resistance
Author: Maraqa, Loaie
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2010
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Abstract:
Tamoxifen remains the therapy of choice for pre-menopausal ERa- positive breast cancer. However, resistance and recurrence remain serious problems. Previous work using Affymetrix microarrays identified 287 genes that were altered in tamoxifen-resistant MCF-7 derivatives. Of these CEACAM6 was significantly up- regulated. The aim of this study was to determine the role of CEACAM6 in endocrine resistant breast cancer and to retrospectively test whether it was predictive of breast cancer recurrence in a large cohort of breast cancers with long term follow up. The role of the related molecule CEACAM5 was also examined. Methods: CEACAM6 expression was investigated using real-time polymerase chain reactions and western blots. The clinical applicability of these findings was examined in' a case-controlled series using tissue microarrays constructed from 350 breast cancer patients. These findings were subsequently validated using an external cohort of unselected primary breast cancer patients (n = 1050). Results: Real-time polymerase chain reaction demonstrated 9-fold up-regulation of CEACAM6 in tamoxifen resistant cells compared to MCF -7 controls. This was confirmed by western blot. CEACAM6 in the initial case-control study was predominantly expressed in primary breast tumours that subsequently relapsed. Odds ratios (OR) for both l0-year Disease Free Survival (DFS) and metastasis was 3.15 (95%CI = 1.82 to 5.45, p
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.579557  DOI: Not available
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