V Scholar Plus Award – extended funding for exceptional V Scholars
Breast cancer is the most common cancer in women. Despite advances in understanding how breast cancer develops, this has not translated into better therapies. The majority of breast cancers are positive for hormone receptors, such as the estrogen and progesterone receptor (PR), and are dependent on these receptors and their hormone ligands (estrogen and progesterone) for growth. However, as tumors progress they become hormone-independent, meaning they grow in the absence of hormones normally required for cell growth, perhaps due to unregulated hormone receptors. It was recently shown that women who were taking hormone replacement therapy that included progesterone had an increased risk of developing breast cancer, underscoring the importance of studying PR in breast cancer. Understanding PR action in the context of breast cancer is important to the development of better therapies.
PR is required during normal breast development and pregnancy, activating genes in the nucleus that stimulate cell growth. Recently, we identified that PR also regulates genes that drive inflammation, a normal cellular process that can function uncontrollably in cancer, generating mutations that may drive cancer growth. Decreasing inflammation has been shown to reduce the risk of developing breast cancer. The objective of the proposed experiments is to determine how PR regulates genes involved in inflammation, and if PR-dependent inflammation can be detected, and eventually blocked, in breast cancer. Understanding how PR regulates inflammation could lead to the development of a new area of therapies for breast cancer, combining currently existing hormone-based therapies with treatment aimed at reducing inflammation