New research provides critical insights into how normal breast precursor cells may be genetically vulnerable to develop into cancer. The research is published June 4th in the inaugural issue of Stem Cell Reports, an open-access journal from the International Society of Stem Cell Research (ISSCR) published by Cell Press. Scientists discovered that a particular class of normal breast precursor cells have extremely short chromosome ends (known as telomeres). As a result, these cells would be expected to be prone to acquiring mutations that lead to cancer if they managed to stay alive. These findings suggest new indicators for identifying women at higher risk for breast cancer and provide insights into potential new strategies to detect, treat, and prevent the disease.
Dr. David Gilley's laboratory at the Indiana University School of Medicine in Indianapolis and Dr. Connie Eaves' laboratory at the BC Cancer Agency's Terry Fox Laboratory in Vancouver, Canada, collaborated to determine how telomeres are regulated in different types of normal breast cells. Their studies revealed that a subset of normal breast precursor cells, called luminal progenitors, have dangerously short telomeres and display a correspondingly high level DNA damage response localized at their chromosome ends. This shows how a normal process of tissue development produces a cell type that is predisposed to acquire cancer-causing mutations.
"This is the first report of a particular normal human precursor cell type that shows such telomere malfunction," says Dr. Eaves. "The luminal progenitors we have found to possess this feature are thus now being brought into the spotlight as a likely stage where breast cancer may 'take off.'" Recent studies have implicated luminal progenitor cells in the development of breast cancers with a mutated BRCA1 gene.
The research highlights the importance of investigating different cell types in normal human tissues to understand the cellular origin of cancer and the factors that may contribute to its development. "An im