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'New' estrogen receptor found to be key player in tamoxifen resistance
Date:10/29/2008

d biophysics and director of GUMC's Biomedical Graduate Research Organization. "It identifies a new player and shows some of its downstream signaling and how this affects responsiveness to tamoxifen in these breast cancers."

The findings came about after the research team developed the first cell culture model of tamoxifen-resistant, invasive lobular carcinoma. To do this, they took cells of this subtype and exposed them to low amounts of tamoxifen and allowed the cells to adapt to the agent. The researchers slowly increased the tamoxifen to match the dosage that a woman taking the drug would be exposed, and during this 10-month process, watched the cells develop resistance to the drug.

"Initially the cells were sensitive to tamoxifen, but as the dose increased, the sensitive cells died off, and the tumor repopulated itself with resistant cells," Riggins says.

During the experiment, the investigators measured gene expression, and were able to track higher and higher expression of the gamma estrogen-related receptor subtype.

"Clearly, the gamma estrogen-related receptors, which have a role in cell metabolism, are stimulating cancer growth, and it is possible that tamoxifen is activating this receptor, " Riggins says.

If alpha estrogen receptors can be used as a drug target, then perhaps the gamma estrogen-related receptor subtype can as well, she adds.


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Contact: Karen Mallet
km463@georgetown.edu
215-514-9751
Georgetown University Medical Center
Source:Eurekalert

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