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Johns Hopkins researchers discover how some breast cancers alter their sensitivity to estrogen
Date:7/27/2011

Using human breast cancer cells and the protein that causes fireflies to glow, a Johns Hopkins team has shed light on why some breast cancer cells become resistant to the anticancer effects of the drug tamoxifen. The key is a discovery of two genetic "dimmer switches" that apparently control how a breast cancer gene responds to the female hormone estrogen.

In a report published online July 7 by Human Molecular Genetics, the scientists show how a gene known as RET in breast cancer cells responds to estrogen by dialing up the manufacture of a signaling protein that instructs cells to divide and causes tumors to become aggressive through the escape from estrogen dependence.

Scientists have long known that breast cancers are either estrogen-receptor positive or estrogen-receptor negative. The positive subset, generally associated with better outcomes for patients, is sensitive to the drug tamoxifen, which blunts aggressive tumor growth through estrogen receptor inhibition, according to Zachary E. Stine, the research team's lead author and a postdoctoral fellow working in the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.

Used for decades to prevent and treat breast tumors that kill about 40,000 women a year, tamoxifen works on some types of breast cancers by interfering with the activity of estrogen. However, resistance to the drug frequently develops over time, and previous experiments by other laboratories have shown that RET plays some role in either altering resistance or maintaining it.

Thus, the Hopkins scientists focused on RET, searching for pieces of DNA in the vicinity of that gene that had the potential, when combined with estrogen, to act as switches controlling the amount of protein product RET manufactures.

After identifying 10 sites in the RET locus that bind with estrogen receptor alpha, the investigators cloned the DNA sequences in those areas,
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Contact: Maryalice Yakutchik
myakutc1@jhmi.edu
443-287-2251
Johns Hopkins Medical Institutions
Source:Eurekalert

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