The role of HP1α and HP1β in breast cancer progression : a thesis presented to Massey University in partial fulfilment of the requirements for the degree of Master of Science in Biochemistry at Massey University, Palmerston North, New Zealand

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Breast cancer is the foremost cause of cancer-related deaths in New Zealand women. Metastasis of breast tumours increases the likelihood of fatality of the disease as treatment becomes more difficult and the tumours may interfere with the function of multiple organ systems. Consequently, the identification of biomarkers that may indicate the potential for a tumour to become metastatic are of great importance and may allow for the selection of more targeted treatment regimes. Heterochromatin Protein 1 (HP1) is a chromatin associating protein that facilitates heterochromatic spreading through its interaction with trimethylated H3K9. There are three HP1 isoforms found in mammals, HP1α, HP1β and HP1γ, each with differing functions and chromatin localisation patterns. Previous research has demonstrated that deregulation of either HP1α or HP1β expression occurs in several types of cancers. Both increases and decreases in HP1α expression have been reported in breast tumour samples, with a decrease in HP1α associated with breast metastases. However, what role loss of HP1α may have in promoting a metastatic phenotype is unclear, and any contribution of HP1β to this process is also explored. This thesis examined the roles of HP1α and HP1β in breast cancer progression through the creation of breast cancer cell lines with knock-down of either HP1α or HP1β. These cell lines were characterised for changes in proliferation, cell cycle profile, global chromatin compaction, invasive potential and anchorage independence. Though no changes were observed in the majority of these characteristics, a novel role for HP1β as a potential suppressor of anchorage independence was identified. Additionally, it was found that HP1α may act to enhance anchorage independence. This information could help to further knowledge of how breast cancer cells proceed towards metastasis, and provide new avenues of research into the potential for levels of HP1α or HP1β to be used as biomarkers for breast cancer progression.
Breast cancer, Heterochromatin protein, Chromatin, Metastasis, Biomarkers, Breast tumour physiology, Cell transformation