Shifts in Cell Lineage Proportions With Aging Raise Cancer Risk

Researchers dig deeper into the mechanisms of breast cancer risk: "Age-related physiological changes, including endocrine profiles and alterations of the microenvironments surrounding breast cells, have been associated with increased cancer risks, but the underlying cellular mechanisms behind these changes and their links to cancer have not been explained. ... Studying the aging process in any human tissue is a challenge primarily because of limited access to samples ... Human mammary epithelial cells (HMECs) are one of the few examples of an epithelial tissue that affords relatively good access because of mastectomies and cosmetic reduction surgeries. In both cases, surgical discards provide sample tissue for research [and researchers] were able to generate a large collection of normal HMEC strains derived from primary tissue in women aged 16 to 91 years. ... [The result was] a study in which it was determined that aging causes an increase in multipotent progenitors - a type of adult stem cell believed to be at the root of many breast cancers - and a decrease in the myoepithelial cells that line the breast's milk-producing luminal cells and are believed to serve as tumor suppressors. ... [Researchers] discovered that in finite-lifespan cultured and uncultured epithelial cells, the advancing years usher in a reduction of myoepithelial cells and an increase in luminal cells that express the proteins keratin 14 and integrin α6. In women under 30, these proteins are expressed almost exclusively in myoepithelial cells. ... The aging process therefore results in both a shift in the balance of luminal/myoepithelial lineages and to changes in the functional spectrum of multipotent progenitors that together appear to increase the potential for malignant transformation. We corroborated our culture data with parallel analyses of in vivo samples, but we still have dots to connect to demonstrate that these changes relate to an increased risk of malignancy. All the signs are there, though."

Link: http://newscenter.lbl.gov/news-releases/2012/06/04/aging-and-breast-cancer/