Further examination of experimental versus control rats demonstrated that use of genistein in puberty cut the number of so-called terminal end buds in the breast. These are the structures that lead to growth of the mammary epithelium, which are the cells lining milk ducts, etc., and it is in these epithelial cells that breast cancer originates. But Hilakivi-Clarke says it is not clear if a mere reduction in the number of these structures could reduce cancer risk, or why.
Other studies suggest that genistein controls expression of genes in terminal end buds that regulate cell growth, repair and death. For example, the chemical could be controlling the ability of stem cells, found on these buds, to reproduce themselves or to differentiate into more specialized cells. There is evidence that suggests that the more stem cells there are on these structures, the greater the risk of breast cancer development, she says. This evidence supports the theory that breast cancer arises from stem cells that have lost growth control.
Other associated research has found that the genes that genistein appears to activate in developing mammary glands are well known --- BRCA1, p53, and PTEN tumor suppressors, Hilakivi-Clarke says. These genes repair genetic damage and control cell survival and death, and they may also help control stem cell reproduction, she says, and genistein apparently up-regulates these genes, boosting production of their beneficial proteins.
What is perhaps most intriguing, she says, is that the same process that protects the breast from excess growth during pregnancy seems to be at work during puberty. In pregnancy, BRCA1 is also up-regulated, perhaps in order to control the fate of stem cells, allowing them to make more cells for
|Contact: Karen Mallet|
Georgetown University Medical Center