Newsworthy Notes
Molecular 'atlas' provides new tool for understanding most common form of breast cancer
Lurking in unexplored regions of the human genome are thousands of previously unknown on/off switches that may influence how the growth of breast cancer is driven by estrogen, a study by Dana-Farber scientists has revealed.
The investigators produced the first complete map of the molecular "control panels" — stretches of DNA that turn genes on and off — operated by the cells' estrogen receptor (ER), the master regulator of cell growth in the most common form of breast cancer. The researchers coined the word "cistrome" to describe the map. ("Cis" refers to a DNA segment that regulates a gene's activity in response to an outside signal.) The map provides a new tool for understanding how genes are regulated and may eventually help researchers and physicians determine which treatments are likely to work best in indvidual patients.
The ER is an intricate protein net in the nucleus of breast cancer cells. When the receptor snares an estrogen molecule, it starts a cascade of activity among genes involved in cell growth and division.
"For the most part, the sequence of steps between the activation of the estrogen receptor and the beginning of tumor cell division has been unclear," says Dana-Farber's Myles Brown, MD, senior author of the study. "We've known of only a handful of the portions of genes that bind to the ER. With this project, we've located all of them and found there are thousands more than were previously known.
"More than 70 percent of breast cancers are ER-positive," meaning their growth is fueled by estrogen, Brown continues, "and the estrogen receptor is the most important target for therapy of these tumors. Knowing the complete set of ER binding sites gives us a new resource for understanding the role of estrogen in breast cancer."
