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thesis Final complete
The cellular evaluation of Tamoxifen resistant breast cancer hormone therapy

A report submitted in part fulfilment of the examination requirements for the award of a B.Sc. (Hons) degree title awarded by the University of Lincoln, June 2014, supervised by Issam Hussain.

Samuel Good
11211175

CERTIFICATE OF ORIGINALITY

This is to certify that I am responsible for the work submitted in this thesis, that the original work is my own, except as specified in the acknowledgements and in references, and that neither the thesis nor the original work contained therein has been previously submitted to any institution for a degree.

Signature:
Name:
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Word count excluding references approx. 9000
Abstract
Breast cancer is one of the leading causes of death in women in western countries (Cancer Research, 2009). There are a number of risk factors which include, gender, age and familial susceptibility. Estrogens are integral regulators in the development of normal breast tissue, however it also plays a role in cancer development and progression (Martin et al, 2000). Tamoxifen is known as a selective estrogen receptor modulator (SERM), it has been the “mainstay of endocrine therapy in breast cancer” (Martin et al, 2000). Tamoxifen is effective when used against estrogen receptor positive (ER+) breast cancers, problems arise when the breast cancer is estrogen receptor negative (ER-). We took two cell lines, MDA MB 231 (ER-) and MCF7/WT (ER+), and tested the ability of Tamoxifen on both. As hypothesised, we discovered that estrogen had a better response when used with the ER+ cell line. To take the research further, we calculated the ED50 for both lines, and found that the ER- negative cell line had a much higher value, again due to its ER status.
The second part of the thesis was aimed at investigating the idea of cancer stem cells (CSC’s) and its cell surface marker CD44 and CSC’s transcription factors OCT4 and NANOG.
CSC’s are a “subpopulation of tumour cells” that



References: Anderson W, Jatoi I, Devesa S (2005). Distinct breast cancer incidence and prognostic patterns in the NCI’s SEER program: Arnes J, Stefansson I, Straume O, Baak J, Lønning P, Foulkes W, et al Benson JR, Jatoi I, Keisch M, Esteva FJ, Makris A, Jordan VC (2009). Early breast cancer. The Lancet 373(9673): 1463-1479. Burmi R, McClelland R, Barrow D, Ellis I, Robertson J, Nicholson R, et al Cancer Research UK (2009a). Breast Cancer Risk Factors Vol. 2009, p Breast Cancer Risk Factors Chen, H., Tritton, T.R., Kenny, N., Absher, M Colditz GA (2005). Estrogen, Estrogen Plus Progestin Therapy, and Risk of Breast Cancer. Clin Cancer Res 11(2): 909s-917. Croix BS, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E, et al Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. (2007). Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence. Clinical Cancer Research 13(15): 4429-4434. Early Breast Cancer Trialists’ Collaborative Group Early Breast Cancer Trialists ' Collaborative G (2011). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant Tamoxifen: patient-level meta-analysis of randomised trials. The Lancet 378(9793): 771-784. Honma N, Horii R, Iwase T, Saji S, Younes M, Takubo K, et al. (2008). Clinical importance of estrogen receptor-beta evaluation in breast cancer patients treated with adjuvant Tamoxifen therapy. J Clin Oncol 26(22): 3727-3734 Hussain, I., Magd, S Martin A-M, Weber BL (2000). Genetic and Hormonal Risk Factors in Breast Cancer. Journal of the National Cancer Institute 92(14): 1126-1135 Musgrove EA, Sutherland RL (2009) Naoto T. Ueno DZ (2011). Targeting EGFR in Triple Negative Breast Cancer. J Cancer 2: 324-328 Neil D Jelly, Issam I Hussain, Jennifer Eremin, Oleg Eremin and Mohamed El-Sheemy Ring A, Dowsett M (2004). Mechanisms of Tamoxifen resistance. Endocrine-Related Cancer 11(4): 643-658 Shou J, Massarweh S, Osborne CK, Wakeling AE, Ali S, Weiss H, et al Weigelt B, Peterse JL, van 't Veer LJ (2005). Breast cancer metastasis: markers and models. Nat Rev Cancer 5(8): 591-602

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