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New mode of action discovered for tamoxifen

IOWA CITY, Iowa -- First used to treat breast cancer more than 30 years ago, tamoxifen now is one of the most widely used breast cancer therapies. University of Iowa researchers have discovered a new mode of action for tamoxifen, which could lead to better targeting of the therapy and possibly the development of new anti-cancer drugs.

In breast tissue, tamoxifen acts as an anti-estrogen, meaning that it blocks the action of the hormone estrogen. Normal breast cells grow in response to estrogen in a controlled fashion. However, in breast cancer, this cell growth is out of control. Treatment with the anti-estrogen tamoxifen inhibits the uncontrolled cell growth and keeps cancer in check.

In a new study, which appears in the Jan. 15 issue of Clinical Cancer Research, researchers based at the Holden Comprehensive Cancer Center at the UI have identified another way that tamoxifen can prevent cancerous growth. The study indicates that tamoxifen treatment causes the re-expression of a tumor suppressor gene known as maspin.

Maspin protein has been shown to inhibit tumor invasion and metastasis, and in normal breast cells, maspin protein is abundant. However, in breast cancer, maspin gene expression is diminished or lost and tumors can form and spread unchecked. Previous studies have shown that reintroducing maspin into breast cancer cells, which have lost the gene expression, causes cancers to be less invasive.

The UI study showed that treatment with tamoxifen turned maspin expression back on in breast cancer cells that had lost the gene expression. The study suggests that one of tamoxifen's beneficial effects is due to its ability to turn maspin expression back on. Moreover, the researchers also found similar results in tissue samples from breast cancer patients who had been treated with tamoxifen.

"Looking at the tumor samples we found up-regulation of maspin in these samples too. That was further confirmation of what we s
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Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-335-9917
University of Iowa
30-Jan-2004


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