Role of the EHF transcription factor in breast cancer

Summary The EHF transcription factor is inactivated in a subset of breast cancers. This project will investigate how loss of this factor contributes to the pathogenesis of this disease and test new treatment strategies based on re-inducing its expression.

Project Details

Role of the EHF transcription factor in breast cancer

EHF is a transcription factor which is highly expressed in the breast epithelium. We recently generated an Ehf knockout mouse, and found that female mice are unable to feed their pups. Examination of the mammary glands of Ehf KO mice revealed a pronounced defect in the development of this tissue during pregnancy. Expression of EHF is also downregulated in human breast cancers, particularly the triple negative subtype, where tumours with low EHF expression have a poorer outcome. Triple negative breast cancers (TNBC’s) comprise ~20% of all breast cancers, and have limited treatment options. There is therefore an urgent need to identify the driver genes which give rise of this subtype so that new treatments can be developed.

Project outline

The goal of this Honours project is to determine the role of EHF in the growth, survival, migration and chemotherapy response in triple negative breast cancer cells.  We will achieve this as follows:

1. Determine the level of EHF mRNA and protein expression in 20 breast cancer cell lines, including 5 TNBC cell lines.

2. Determine the effect of EHF re-expression on cell proliferation, survival, migration and response to chemotherapy in TNBC cells.

3. Determine the effect of EHF knockdown in TNBC cells which express EHF on cell proliferation, survival, migration and response to chemotherapy.

4. Identify the target genes of EHF in TNBC cells following EHF knockdown or overexpression.

The student undertaking this project will learn the fundamental concepts of cancer biology, and use a variety of techniques including working with cell line models of breast cancer, western blotting, immunohistochemistry, transfections and assessing response to drug treatment.