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Mechanism of metastasis of triple negative breast cancer

Al-Zubaidi, Makarim Atiyah Kadhim (2019) Mechanism of metastasis of triple negative breast cancer. PhD thesis, University of Essex.

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Abstract

Triple Negative Breast Cancer (TNBC) is increasingly recognised as a serious, worldwide public health concern. TNBC has the ability to recur after treatment and appears to be greatest in the first few years. The phenotypical changes of the TNBC metastasis represent a unique that heterogeneous tumour cell population with special biological features that permit travel to distant sites and the establishment of a clinically disseminated disease. Triple-negative tumours do not express the oestrogen-ERα receptor, progesterone PgR receptor and the epidermal growth factor receptor (Her2). However, the three biomarkers are used clinically to guide treatment. The main aim of this research is to elucidate recently identified molecular pathways that contribute to TNBC metastasis. It also provides a useful approach to understand the heterogeneity of TNBC at its different stages. Several protein candidates show differential expression between metastatic and non-metastatic tumours. This research had hypothesised that over expression by the group of proteins increases the metastatic propensity of TNBC. In this research, I studied selected protein candidates extracted from human breast cancer tumour tissue and breast cancer cell lines (MDA-MB- 468 and MCF-7) using quantitative detection by in-gel digestion mass spectrometry and proteomics, western blotting (WB), immunocytochemistry (ICC), CRISPR/Cas9 and Wound Healing. Here, I used the CRISPR/Cas9 techniques to induce EGFR and STAT1 over expression and then performed wound-healing experiments, which revealed that STAT1 over expression from its genomic locus significantly, decreased the potential of the cells to close the wound. Also, the present study demonstrates the over expression of EGFR in 26 tumour samples of TNBC patients with a p-value < 0.05. The data obtained provides valuable information in order to understand the mechanisms of metastasis.

Item Type: Thesis (PhD)
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Makarim Al-Zubaidi
Date Deposited: 08 Jan 2020 13:17
Last Modified: 08 Jan 2020 13:17
URI: http://repository.essex.ac.uk/id/eprint/26314

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