The ETS transcription factor E74-like-factor 5 (Elf5) is an epithelial restricted protein found in the mammary gland, kidney, salivary gland and stomach. In the mammary gland, Elf5 expression dramatically increases during pregnancy and high levels of Elf5 are maintained throughout lactation. Elf5 is downstream to the prolactin receptor and is necessary for lobuloalveolar development and milk production. It has been found that Elf5 drives the production of alveolar cells from the luminal progenitor cell in the mammary gland cell hierarchy. We have pursued a developmental understanding of the normal growth and development that occurs in the mammary gland, which encompasses proliferation, apoptosis and invasion, in order to understand molecular pathways which breast cancer cells utilise. In human breast cancers it has been shown that, when compared to patient-matched microdissected controls, Elf5 is one of the most consistently downregulated genes at all stages of breast cancer. Elf5 expression is consistently lower in the luminal subgroups relative to basal subgroups of breast cancer, suggesting a crucial role for Elf5 in both tumour initiation and subgroup determination. By using the metastatic breast cancer mouse model MMTV-PyMT we have found that inducing the overexpression of Elf5 leads to a change in the proliferative ability of the primary tumour cells. We hypothesised that overexpression of Elf5 may also change the metastatic phenotype of breast cancer cells.
Using differentially expressed surface proteins in lung and mammary epithelium we are able to purify breast cancer metastatic cells from the lung of PyMT animals. Following a genome wide expression profiling approach, we are studying the cellular effect of Elf5 on lung metastasis in comparison with the primary tumour cells in the MMTV-PyMT mouse model. In addition, we have developed an inducible model for Elf5 overexpression coupled with luciferase. Metastatic human cancer cell lines carrying this construct are used to create mouse xenografts, allowing us to explore the role of Elf5 on metastasis in vivo using a combination of in vivo imaging and cell sorting. This will allow study of key genes involved in the progression to metastasis. While Elf5 has previously been identified to be involved in mouse mammary gland development, this is the first look at its role in cancer and progression to metastasis.