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Abstract
Thesis abstract: Breast cancer represents a leading cancer-related diagnosis of Australian women, with treatments ultimately still ineffective for many patients. Investigating the mechanisms behind normal breast development is a means to identify processes involved in carcinogenesis, as they are frequently corrupted to facilitate tumour initiation and progression. The PRL signaling pathway is vital for the function of the mammary tissue during pregnancy and lactation. The mouse ELF5 and its human counterpart, ESE2, were identified as downstream targets of this pathway and have subsequently been characterised as crucial players in mammary gland development. In addition, limited evidence has pointed to the possibility of this protein being involved in human breast carcinogenesis, although a direct link remains pending. The current body of work was aimed at exploring the role of the human ESE2 in breast cancer. This was achieved through the use of a range of large and small-scale in vitro techniques to, firstly, attempt to identify potential ESE2 binding partners. Secondly, a model of inducible, stable ESE2 downregulation was employed to establish the function of ESE2 in the T47D breast cancer cell line, in the context of progesterone signaling, which is an important mediator of normal and aberrant mammary gland behaviour. It was determined that inhibiting a progestin-mediated ESE2 increase led to the augmentation of the previously characterised anti-proliferative effects of this hormone. An equivalent overexpression model was generated and characterised in detail. Negative effects of ESE2 on cell proliferation and adhesion were identified and were accompanied by changes at the level of apoptosis, gene transcription activity and other molecular changes. The data gathered is the first study to directly examine the role of ESE2 in human breast cancer.