Local oestrogen production within the breast is critically important for breast cancer progression. While the genetic factors that contribute to estrogen production are fairly well understood, epigenetic factors are much less well studied. Understanding these factors is critical to the development of tissue-specific strategies to inhibit this process.
Development of breast cancer is characterised by a variety of genetic lesions including gene amplifications and deletions, point mutations, chromosomal rearrangements and overall aneuploidy. One of the most common molecular alterations in cancer is epigenetic change. Epigenetics describes a trait that is heritable, yet not based upon a change in primary DNA sequence.
These epigenetic changes occur at a higher frequency than genetic changes, occur at defined regions in a gene, and most importantly are reversible upon treatment with pharmacological agents. DNA methylation is one well-known epigenetic mechanism that has a clear synergy with alterations in gene regulation that is associated with the onset of a developing cancer.
We have shown that aromatase is under epigenetic regulation in breast cells and are currently expanding this theme to investigate the epigenetic regulation of key genes involved in estrogen synthesis.
This research has received funding from the Victorian Breast Cancer Research Consortium and the US Department of Defence Congressionally Directed Medical Research Programs.
Tohuku University, Sendai, Japan
Walter & Eliza Hall Institute, Melbourne
Peter MacCallum Cancer Centre, Melbourne