OpenAIRE is about to release its new face with lots of new content and services.
During September, you may notice downtime in services, while some functionalities (e.g. user registration, login, validation, claiming) will be temporarily disabled.
We apologize for the inconvenience, please stay tuned!
For further information please contact helpdesk[at]

fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Francies, Hayley E.
Languages: English
Types: Doctoral thesis
Subjects: RC0254

Classified by OpenAIRE into

mesheuropmc: skin and connective tissue diseases
In ER+ breast cancer initial responses to antihormones are variable, complete\ud responses are rare and resistance is eventually acquired by many patients. It is\ud important to model these events to discover predictive markers of antihormone\ud outcome and so targeted strategies can be developed to maximise antihormone\ud effectiveness. To date, most studies have employed the MCF-7 cell line which fails\ud to represent the variability of ER+ disease. Focusing on Faslodex, the thesis\ud objective was to use 4 cell lines in vitro encompassing ER+/HER2- (MCF-7/T47D)\ud and ER+/HER2+ (BT474/MDA-MB-361) disease to (i) characterise the magnitude of\ud initial antihormone response, (ii) monitor the onset of resistance by prolonged\ud treatment and (iii) detail gene expression changes during Faslodex treatment.\ud All models were initially growth-inhibited by Faslodex, with superior responses in\ud HER2- lines. Microarray analysis revealed gene cohorts affected by Faslodex\ud treatment differed between HER2+ and HER2- models. While MCF-7, BT474 and\ud MDA-MB-361 cells acquired Faslodex resistance, this failed to develop in the T47D\ud line, providing a model of complete-response. A filtering process identified genes\ud involved in the varying Faslodex responses and clinical relevance was determined\ud using the NEWEST Faslodex clinical trial dataset.\ud Of interest was the Faslodex-induction of CXCR4, as a potential mediator of\ud acquired resistance, while suppression of the RET signalling pathway related to\ud improved initial response in the ER+/HER2- setting. Importantly up-regulation of\ud DCN by Faslodex was associated with improved Faslodex response in T47D cells and\ud also with proliferation (Ki67) fall in the NEWEST clinical trial. shRNA knockdown of\ud DCN reduced the sensitivity of T47D cells to Faslodex and enabled development of\ud resistance.\ud This thesis has successfully identified novel elements of Faslodex response and\ud resistance and further work is now required to clarify the importance of these\ud mediators and to determine if DCN could prove a useful clinical biomarker of\ud Faslodex response.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • She, Q-B., Chandarlapaty, S., Ye, Q., Lobo, J., Haskell, K. M., Leander, K. R., DeFeo-Jones, D., Huber, H. E., Rosen, N. Breast cancer cells with PI3K mutation or HER2 amplification are selectively addicted to Akt signalling. PLos ONE 2008: 3: [Epub]
    • Sheth, S. S., Bodnar, J. S., Ghazalpour, A., Thipphavong, C. K., Tsutsumi, S., tward, A. D., Demant, P., Kodama, T., Aburatani, H., Lusis, A. J. Hepatocellular carcinoma in Txnip-deficient mice. Oncogene. 2006: 25: 3528-353
    • Shimamura, S., Sasaki, K., Tanaka, M. The Src substrate SKAP2 regulates actin assembly by interacting with WAVE2 and cortactin proteins. Journal of Biological Chemistry 2013: 288: 1171-1183 Shim, W. S., Conaway, M., Masamura, S., Yue, W., Wang, J. P., Kmar, R., Santen. R. J. Estradiol hypersensitivity and mitogen-activated protein kinase expression in long-term estrogen deprived human breast cancer cells in vivo. Endocrinology 2000: 141: 396-405.
    • Shou, J., Massarweh, S., Osborne, C. K., Wakeling, A. E., Ali, S., Weiss, H., Schiff, R. Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. Journal of the National Cancer Institute 2004: 96: 926-935
    • Simoncini, T., Maffei, S., Basta, G., Barsacchi, G., Genazzani, A.R., Liao, J.K., De Caterina, R. Estrogens and glucocorticoids inhibit endothelial vascular cell adhesion molecule-1 expression by different transcriptional mechanisms. Circulation Research 2000, 87; 19-25.
    • Siskind, V., Schofield, F., Rice, D., Bain, C. Breast cancer and breast feeding: results from an Australian case-control study. American Journal of Epidemiology 1989: 130: 229-236 Slamon, D. J., Clark, G. M., Wong, S. G., Levin, W. J., Ullrich, A., McGuire, W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987: 235: 177-182
    • Skobe, M., hawighorst, T., Jackson, D. G., Prevo, R., Janes, L., Velasco, P., Riccardi, L., Alitalo, K., Claffey, K., Detmar, M. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nature Medicine 2001: 7: 192-198
    • Smith, C. L., Nawaz, Z., O'Malley, B. W. Coactivator and corepressor regulation of the agonist/antagonist activity of the mixed antiestrogen, 4-hydroxytamoxifen. Molecular Endocrinology 1997, 11; 657-666
    • Smith, M. C., Luker, K. E., Garbow, J. R., Prior, J. L., Jackson, E., Piwnica-Worms, D., Luker, G. D. CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Research 2004: 64: 8604-8612
    • Smith, I. E., Walsh, G., Skene, A., Llombart, A., Mayordomo, J. I., Detre, S., Salter, J., Clark, E., Magill, P., Dowsett, M. A phase II placebo-controlled trial of neoadjuvant anastrozole alone or with gefitinib in early breast cancer. Journal of Clinical Oncology 2007: 25: 3816-3822
    • Spector, N. L., Blackwell, K. L. Review Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer. Journal of Clinical Oncology 2009: 27: 5838-5847
    • Tang, J. Z., Kong, X. J., Kang, J., Fielder, G. C., Steiner, M., Perry, J. K., Wu, Z. S., Yin, Z., Zhu, T., Liu, D. X., Lobie, P. E. Artemin-stimulated progression of human non-small cell lung carcinoma is mediated by BCL2. Molecular Cancer Therapeutics 2010: 9: 1697-1708
    • Teicher, B. A., Fricker, S. P. CXCL12 (SDF-1)/CXCR4 Pathway in Cancer. Clinical Cancer Research 2010: 16: 2927-2931
    • Teixeira, C., Reed, J. C., Pratt, M. A. Estrogen promotes chemotherapeutic drug resistance by a mechanism involving Bcl-2 proto-oncogene expression in human breast cancer cells. Cancer Research 1995: 55: 3902-3907
    • Teyssier, C., Belguise, K., Galtier, F., Chalbos, D. Characterization of the physical interaction between estrogen receptor alpha and JUN proteins. Journal of Biological Chemistry 2001, 276; 36361-36369 Teutschbein, J., Haydn, J. M., Samans, B., Krause, M., Eilers, M., Schartl, M., Meierjohann, S. Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins. BMC Cancer 2010: 10: [Epub]
    • Thiery, J. P., Sleeman, J. P. Complex networks orchestrate epithelial-mesenchymal transitions. Nature Reviews Molecular Cell Biology 2006: 7: 131-142.
    • Thornberry, N., Bull, H., Calaycay, J., Chapman, K., Howard, A., Kostura, M., Miller, D., Molineaux, S., Weidner, J., Aunins, J., Elliston, K., Ayala, J., Casano, F., Chin, J., Ding, G., Egger, L., Gaffney, E., Limjuco, G., Palyha, O., Raju, S., Rolando, A., Salley, J., Yamin, T., Lee, T., Shively, J., MacCross, M., Mumford, R., Schmidt, J., Tocci, M. A novel heterodimeric cysteine protease is required for interleukin-1 β processing in monocytes. Nature 1992: 356: 768-774
    • Tian, M., Schiemann, W. P. The TGF-beta paradox in human cancer: an update. Future Oncology 2009: 5:259-271
    • Thrane, S., Lykkesfeldt, A. E., Larson, M. S., Sorenson, M. S., Yde, C. W. Estrogen receptor α is the major driving factor for growth in tamoxifen-resistant breast cancer and supported by HER/ERK signaling. Breast Cancer Research and Treatment 2013: 139: 71-80
    • Tobler, N. E., Detmar, M. Tumor and lymph node lymphangiogenesis-impact on cancer metastasis. Journal of Leukocyte Biology 2006: 80:691-696
    • Tralhao, J. G., Schaefer, L., Micegiva, M., Evaristo, C., Schonherr, E., Kaval, S., Veiga-Fernandes, H., Danel, C., Iozzo, R. V., Kresse, H., Lemarchand, P. In vivo selective and distant killing of cancer cells using adenovirus-mediated decorin gene transfer. FASEB Journal 2003: 17: 464-466 Troiani, T., Vecchione, L., Martinelli, E., Capasso, A., Constantion, A., Ciuffreda, L. P., Morgillo, F., Vitagliano, D., D'Aiuto, E., De Palma, R., Tejpar, S., Van Cutsem, E., De Lorenzi, M., Caraglia, M., Berriono, L., Ciardiello, F. Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase A activation in human lung and colorectal cancer cells. British Journal of Cancer 2012: 106: 1648-1659
    • Troup, S., Njue, C., Kliewer, E. V., Parisien, M., Roskelley, C., Chakravarti, S., Roughley, P. J., Murphy, L. C., Watson, P. H. Reduced expression of the small leucine-rich proteoglycans, lumican, and decorin is associated with poor outcome in node-negative invasive breast cancer. Clinical Cancer Research 2003: 9: 207-214
    • Wu, X. R., Kong, X. P., Pellicer, A., Krebich, G., Sun, T. T. Uroplakins in urothelial biology, function, and disease. Kidney International 2009: 75: 1153-1165
    • Yagi, H., Tan, W., Dillenburg-Pilla, P., Armando, S., Amornphimoltham, P., Simaan, M., Weigert, R., Molinolo, A. A., Bouvier, M., Gutkind, J. S. A synthetic biology approach reveals a CXCR4-G13-Rho signaling axis driving transendothelial migration of metastatic breast cancer cells. Science Signalling 2011: 4: [Epub]
    • Yamanaka, S., Olaru, A. V., An, F., Luvsaniav, D., Jin, Z., Agarwal, R., Tomuleasa, C., Popescu, I., Alexandrescu, S., Dima, S., Chivu-Economescu, M., Montgomery, E. A., Torbenson, M., Meltzer, S. J., Selaru, F. M. MicroRNA-21 inhibits Serpini1, a gene with novel tumour suppressive effects in gastric cancer. Digestive Liver Disease 2012: 44: 589-596
    • Yang, C., Yu, B., Zhou, D., Chen, S. Regulation of aromatase promoter activity in human breast tissue by nuclear receptors EAR-2, COUP-TF1 (EAR-3), and RARγ. Oncogene 2002: 21: 2854-2863 Yang, C., Zhou, D., Chen, S. Modulation of aromatase expression in the breast tissue by ERRα-1 orphan receptor. Cancer Research 1998: 58: 5695-5700
    • Yang, J. D., Seol, S. Y., Leem, S. H., Kim, Y. H., Sun, Z., Thorgeirsson, S. S., Chu, I. S., Roberts, L. R., Kang, K. J. Genes associated with recurrence of hepatocellular carcinoma: integrated analysis by gene expression and methylation profiling. Journal of Korean Medical Sciences 2011: 26: 1428-1438 Yarden, R. I., Wilson, M. A., Chrysogelos, S. A. Estrogen suppression of EGFR expression in breast cancer cells: a possible mechanism to modulate growth. Journal of Cellular Biochemistry Supplements 2001: Supplement 36: 232-246
    • Yip-Schneider ,M. T., Lin, A., Marshall, M. S. Pancreatic tumor cells with mutant K-ras suppress ERK activity by MEK-dependent induction of MAP kinase phosphatase-2. Biochemical and Biophysical Research Communications. 2001: 280: 992-997
    • Yu, F. X., Zhang, Y., Park, H. W., Jewell, J. L., Chen, Q., Deng, Y., Pan, D., Taylor, S. S., Lai, Z. C., Guan, K. L. Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation. Genes and Development 2013: 27: 1223-1232
    • Zeelenberg, I. S., Ruuls-Van Stalle, L., Roos, E. The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases. Cancer Research 2003: 63: 3833-3839 Zekri, A. R., Hassan, Z. K., Bahnassy, A. A., Sherif, G. M., Eldahshan, D., Abouelhoda, M., Ali, A., Hafez, M. M. Molecular prognostic profile of Egyptian HCC cases infected with hepatitis C virus. Asian Pacific Journal of Cancer Prevention 2012: 13: 2433-5438
    • Zhang, X., Diaz, M. R., Yee, D. Fulvestrant regulates epidermal growth factor (EGF) family ligands to activate EGF receptor (EGFR) signaling in breast cancer cells. Breast Cancer Research and Treatment 2013: 139: 351-360
  • No related research data.
  • Discovered through pilot similarity algorithms. Send us your feedback.

Share - Bookmark

Cite this article

Cookies make it easier for us to provide you with our services. With the usage of our services you permit us to use cookies.
More information Ok