Breast cancer
Breast cancer is the most common cause of cancer in women, accounting for 30 per cent of all cancers affecting women. One in nine women in Australia will develop this disease by the age of 85. Breast cancer represents a huge challenge in terms of improving cancer outcomes for patients and their families.
One of our key research areas is to try to understand the cells that give rise to breast cancer and to delineate the key signalling pathways that become disrupted in these cells during cancer development. Towards this end we have been investigating the mammary stem cell and its descendents in normal breast tissue and identifying master regulator genes that control normal development. Aberrant signalling by transcriptional regulatory genes often underpins cancer development.
Our team is deciphering the cellular and molecular controls on normal breast development and determining how these controls break down to cause breast cancer. Key areas of research in the breast cancer laboratory include the identification of normal breast cell types, of molecular regulators that control cell proliferation and maturation, and cell types that are predisposed to carcinogenesis.
In 2006, we identified the mammary stem cell and showed that a single rare cell isolated from a mouse mammary gland could generate a fully functional mammary gland. Recently we extended these studies to human breast tissue, where we isolated stem, progenitor and mature cells from normal breast tissue and showed that they share remarkable functional properties with those in the mouse mammary gland. Molecular profiling of the different subsets of cells showed that a large number of genes are conserved across species, highlighting the utility of mouse models to understand mammary development and breast cancer.
One of our key working hypotheses is that the different sub-types of breast cancer arise in different types of breast epithelial cells. Using the cellular hierarchy as a framework, we have discovered that ductal progenitors are the likely culprits for breast cancers that develop in women carrying a BRCA1 mutation. The cells were found to be expanded and exhibited aberrant growth properties.
In collaboration with Associate Professor Gordon Smyth’s group in the Bioinformatics Division, we further showed that the gene profiles of basal breast cancers (an aggressive subtype) were most similar to that of ductal progenitor cells, suggesting that these cells go awry in individuals that develop basal breast cancer. This study also revealed a number of markers over-expressed by the perturbed progenitor cells, potentially providing novel therapeutic targets to be tested in the preclinical models of breast cancer that we have developed in our laboratory.