Investigating the role of CBX2 in models of triple negative breast cancer

Warren, Chloe

Abstract

Breast cancer accounts for around 11,500 deaths per year in the UK in women. There are several subtypes of breast cancer including triple negative breast cancer (TNBC) which is categorised by a lack of oestrogen, progesterone and human epidermal growth factor 2 (HER2) hormone receptor expression. The prognosis for patients with TNBC is poor as it is an aggressive subtype of the disease that currently lacks any targeted therapeutics and is therefore hard to treat. The identification of novel therapeutic targets for TNBC is therefore crucial.

Epigenetics is the study of gene expression control via chemical modification of DNA and histone proteins. Recent studies have shown that altered histone modification is linked with cancer development. Epigenetic regulatory proteins may therefore be a source of novel therapeutic targets in cancer. CBX2 is an epigenetic reader protein and is part of the polycomb repressive complex 1 (PRC1). Expression of CBX2 is increased in TNBC compared to normal breast tissue indicating that it may play a role in the progression of this disease. This study aimed to investigate the function of CBX2 in TNBC by downregulating CBX2 expression in TNBC cell line models by RNA interference (RNAi) and analysing phenotypic and gene expression changes. We identified that CBX2 is present in an active phosphorylated form in TNBC cells and that cell proliferation decreased when CBX2 was knocked down. We identified that the expression of cell cycle regulatory genes such as Cyclin D1 (CCND1), CCND3, CCNA2 CDK1 and CDK4 decreased when CBX2 was knocked down and RNA-Seq analysis in TNBC cells following CBX2 knockdown showed that differentially expressed genes were associated with the cell cycle and multiple oncogenic signalling pathways. These results suggest that CBX2 may play a key role in TNBC development and may therefore be a potential future therapeutic target.

Citation

Warren, C. (2019). Investigating the role of CBX2 in models of triple negative breast cancer. (Thesis). University of Hull. Retrieved from https://hull-repository.worktribe.com/output/4222872

• Thesis Type: Thesis
• Deposit Date: Feb 25, 2021
• Publicly Available Date: Feb 23, 2023
• Keywords: Biomedical sciences
• Public URL: https://hull-repository.worktribe.com/output/4222872
• Additional Information: Department of Biomedical Sciences, The University of Hull
• Award Date: Sep 1, 2019