Investigating the role of CBX2 in ER- positive breast cancer

Waters, Ella Jane

Abstract

Breast cancer is the most common form of cancer in women, with oestrogen receptor (ER) positive breast cancers being the most common subtype. Although there are targeted endocrine therapies for this receptor, resistance mechanisms mean that they are not always effective. Post-translational modifications of histone proteins are important for regulating gene expression. It is known that the pattern of modifications is different in cancerous tissue compared to normal tissue. Epigenetic reader proteins recognise histone post-translational modifications and help remodel the adjacent chromatin landscape, resulting in gene expression or repression. This means epigenetic reader proteins are possible novel therapeutic targets. CBX2 is an example of an epigenetic reader protein which is overexpressed in ER-positive breast cancer. The aim of this study was to analyse the role of CBX2 in ER-positive breast cancer. This was assessed by knocking down CBX2 gene and protein expression, using siRNAs in MCF-7 and T47D cell lines and analysing changes to cellular phenotype and gene expression regulation. It was determined that CBX2 in the breast cancer cell lines was a nuclear activated phosphorylated form of the protein, and that knockdown of CBX2 has little effect on H2AK119ub and H3K27me3, but causes decrease of H3K27ac. Phenotypic experiments analysed the effect of CBX2 on cell growth, using MTS and apoptosis assays, and showed that CBX2 knockdown reduced cell number and increased cell death. RNA- Sequencing analysis identified that CBX2 has a role in regulating genes within the cell cycle and ER-signalling pathway. The effect on ER-target genes was validated by quantitative-PCR. Additional investigation of the RNA-Seq data will further validate the role of CBX2 in ER-positive breast cancer. Continued research is important for developing therapies for the future treatment of this cancer.

Citation

Waters, E. J. (2019). Investigating the role of CBX2 in ER- positive breast cancer. (Thesis). University of Hull. Retrieved from https://hull-repository.worktribe.com/output/4222704

• Thesis Type: Thesis
• Deposit Date: Oct 16, 2020
• Publicly Available Date: Feb 23, 2023
• Keywords: Biomedical sciences
• Public URL: https://hull-repository.worktribe.com/output/4222704
• Additional Information: Department of Biomedical Sciences, The University of Hull
• Award Date: Sep 1, 2019