In the October issue of Nature Genetics, the investigators present the first complete map of the molecular "control panels" -- stretches of DNA that turn genes on and off -- operated by the cells' estrogen receptor, the master regulator of cell growth in the most common form of breast cancer. The map, which includes thousands of such control regions, provides scientists with a new tool for understanding how genes are regulated, and may eventually help doctors match patients with treatments that are most likely to be effective for them and overcome the problem of resistance to current hormone therapies, the study authors say.
The estrogen receptor (ER) is an intricate protein net in the nucleus of breast cancer cells. When the receptor snares an estrogen molecule, it sets in motion a cascade of activity among genes involved in cell growth and division. In many breast tumors, cells have an unusually large number of ERs, so they proliferate rapidly in the presence of estrogen. Drugs that block the ER, such as tamoxifen and fulvestrant, are often able to stop or slow the growth of these estrogen-driven tumors.
"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. We've known of only a handful of the portions of genes that bind to the ER -- the so-called control regions that activate or deactivate the genes," says Dana-Farber's Myles Brown, MD, the senior author of the new study. "With this project we've located all of them, and found there are thousands more than were previously known." Since most genes have more than one control region, the map points to about 1,000 genes influenced, to some degree, by the E
Source:Dana-Farber Cancer Institute