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
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.