Breast cancer could be prevented by targeting epigenetic proteins

Researchers found that epigenetic proteins promote the proliferation of mammary gland stem cells in response to the sex hormone progesterone. Mammary glands contain two types of cells, basal and luminal that arise from specialized stem or progenitor cells. During pregnancy or the menstrual cycle, progesterone induces basal and luminal progenitor cell numbers to expand and drive mammary gland formation. But mammary gland progenitors may also give rise to cancer. Progesterone exposure and stem cell proliferation have been linked to the development of breast cancer, and the number of progenitor cells is often elevated in women carrying mutations in BRCA1 or other genes that put them at a high risk of developing the disease.

Currently, there are no standard of care preventative interventions for women at high risk of breast cancer, although it is becoming increasingly clear that stem and progenitor cells underlie cancer development, we lack strategies to target these cells for chemoprevention. “The progenitor cells and identifies any vulnerability that could potentially be exploited to prevent the development of breast cancer. The RNA molecules produced by mammary gland cells. Now they quantified all of the cells' proteins and assessed the cells' epigenomes -the various chemical modifications to chromosomes that help determine which genes are turned on and off. Several of these drugs inhibited the proliferation of mammary gland progenitor cells and decreased their total number in mice. One, a drug called decitabine that inhibits DNA methyltransferase enzymes and is approved to treat myelodysplastic syndrome, delayed the formation of tumours in breast cancer-prone rodents.

Scientists then tested the effects of epigenetic inhibitors on mammary gland progenitor cells isolated from women at high risk of developing breast cancer. Progenitor cells from patients with BRCA1 mutations were particularly vulnerable to epigenetic inhibitors, including decitabine. Decitabine also suppressed the activity of progenitor cells from patients with mutations in the BRCA2 gene. “This demonstrates that the dependency of progenitor cells on specific epigenetic proteins is conserved between mice and humans and highlights the potential of epigenetic therapies to target these important cell types in the human breast as a form of chemoprevention.