Chemoprophylaxis of cancer
Researchers from the Princess Margaret Cancer Center in Toronto found that methylated proteins promote the proliferation of breast stem cells under the influence of progesterone. Drug inhibition of enzymes that attach methyl groups to proteins can prevent the development of breast cancer in women at high risk of the disease.
The mammary gland contains two types of cells: basal and luminal. They are formed from progenitor (specialized stem) cells. During pregnancy or during a certain phase of the menstrual cycle, progesterone stimulates progenitor progenitor cells of basal and luminal cells to expand the network of milk ducts.
This mechanism can also lead to cancer. The long-term effect of progesterone and the proliferation of stem cells are associated with the development of breast cancer. The number of progenitor cells is often increased in carriers of BRCA1 mutations and other genes, the presence of which puts women at high risk.
Currently, there is no standard of preventive interventions for women at risk of breast cancer. And although the role of progenitor cells in the progression of cancer is already obvious, there are no chemoprophylaxis strategies targeting these cells.
The researchers studied changes in the mammary gland cells of mice in response to the effects of progesterone. They identified all cell proteins and evaluated epigenomes – various chemical modifications of cell chromosomes that help determine which genes are turned on or off.
This broad review of breast cells showed that progesterone contributes to an increase in the activity of regulatory proteins responsible for chromosome changes in progenitor, to a greater extent luminal, cells.
The researchers suggested that the suppression of these proteins may stop the proliferation of progenitor cells in response to the effects of progesterone. They tested several epigenesis inhibitors on animals, many of which are already approved by the FDA for the treatment of various diseases. Some drugs were able to block the proliferation of breast progenitor cells and reduced their total number in mice. Decitabine, a drug that inhibits DNA methyltransferase enzymes and is approved for the treatment of myelodysplastic syndrome, has led to a delay in tumor formation in rodents prone to breast cancer.
DNA methyltransferase-1 (green) in luminal cells of the ducts of the breast before (left) and after (right) decitabine treatment. Source: article in the Journal of Cell Biology.
In breast cancer progenitor cell cultures taken from high-risk women, decitabine suppressed the activity of progenitor cells with BRCA1 and BRCA2 gene mutations.
The results of the study confirm the potential of epigenetic therapy aimed at preventing the development of breast cancer.
Article by A. E. Casey et al. Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities published in the Journal of Cell Biology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to EurekAlert: Breast cancer could be prevented by targeting epigenetic proteins, study suggests.