Regulation of drug and xenobiotic UDP glucuronosyltransferases
Some chemicals made in the body or from the environment may initiate breast cancer. Once the cancer begins, the estrogen hormone fuels its growth. We are investigating an enzyme that inactivates chemical carcinogens and controls estrogen levels in the breast. In addition to estrogen, the breast is exposed to androgen from the blood and it is thought that androgen may counteract the positive influence of estrogen on breast cancer growth. Hence, enzymes that inactivate androgens in the breast are also important in controlling estrogen-driven cancer growth.
We have found that the levels of enzymes that inactivate and remove androgens and estrogen are related to how well the cancer cell responds to either androgen or estrogen. Up to 100-fold variations in the levels of these enzymes were observed, indicating their suitability as targets for controlling estrogen-mediated growth of breast cancer cells. We have also identified a major mechanism regulating the two androgen-inactivating enzymes.
What we aim to achieve
We aim to increase our knowledge of the mechanisms that result in the removal of carcinogens and steroids which drive breast cancer growth. This research will provide the framework for the design of therapeutic strategies aimed at increasing the levels of the enzymes that protect against chemical carcinogens and reduce the deleterious effects of excessive estrogen action on cancer growth. Knowledge of these mechanisms will also help in the design of diagnostic tests to aid in predicting breast cancer risk. These may include gene-based tests to identify defects that alter the expression of enzymes that remove carcinogens and dampen excess estrogen action.
Our next steps and milestones
The findings of the project will be expanded to look for small molecules that can support breast cells to detoxify and aid in the removal of the drivers of breast cancer growth. These molecules would be designed to induce the expression of the enzymes involved in inactivating carcinogens and steroid hormones.
What motivates me
I am motivated to understand how we can protect normal cells from carcinogens and reduce cancer growth and, in the process, find markers that might indicate that a particular individual may be at increased risk of developing a particular cancer.
My message to supporters
Funding from Cancer Council SA donors has enabled me to initiate this project looking at enzymes in breast cancer that inactivate and remove carcinogens and steroid hormones. This research would not have started nor attracted funding from the NHMRC without this generous support.