Targeting Epigenetic Proteins to Prevent Breast Cancer

Breast cancer can occur in both women and men, and arises from the proliferation of abnormal cells. Mammary glands contain two types of cells, basal and luminal, which are formed from specialized stem or progenitor cells. The sex hormone, progesterone, can surge and induce these cells to increase mammary gland formation during pregnancy or menstruation. Epigenetic proteins can trigger stem cell proliferation in response to the increased levels of progesterone. Unfortunately, progesterone has been linked to the development of breast cancer. The number of progenitor cells is often higher in women carrying BRCA1 mutations and other genes that increase the risk of developing cancer. At this time, there are no standard preventative strategies targeting stem and progenitor cells for women at high risk of cancer.

A recent report suggests epigenetic proteins promote the proliferation of mammary gland stem cells in response to progesterone. Researchers isolated cells from the mammary glands of mice and examined the effects of exposure to progesterone. Protein levels were quantified, which indicated upregulation of epigenetic regulatory proteins that can modify chromosomes. Multiple epigenetic inhibitors that inhibited the proliferation of mammary gland progenitor cells, including FDA approved drugs, were tested. One drug, decitabine, that inhibits DNA methyltransferase enzymes, was found to reduce tumor development in cancer-prone rodents. Furthermore, progenitor cells from BRCA1 mutation patients were shown to be vulnerable to epigenetic inhibitors. Targeted drug inhibition of epigenetic proteins could prevent the development of breast cancer in women with a high risk of the disease.

For more information: http://jcb.rupress.org/content/early/2018/06/18/jcb.201804042

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