Weill Cornell team identifies potential new drug targets against hormone-dependent bre...(ls of cancer-causing estrogen in breast ...),Health
ls of cancer-causing estrogen in breast tissues."
In 2006, researchers led by Dr. Dannenberg discovered that cyclooxygenase (COX) protein-derived prostaglandin E2 (PGE2) could turn on the gene that expresses aromatase. More recently, the healthy form of the BRCA1 tumor-suppressor gene was found to quiet the aromatase gene -- performing its duty in keeping breast cancer risk low.
"Maintaining this BRCA1-aromatase relationship in a healthy balance may help to keep patients free of hormone-dependent breast cancer," Dr. Dannenberg explains.
Studies have shown that use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) can also dampen PGE2 production and aromatase activity. COX-2 inhibitors (which include Vioxx and Celebrex) may do the same. However, these drugs also suppress a prostanoid that helps protect the heart, and in 2004 Vioxx was withdrawn from the market due to an excess of cardiovascular events noted in long-term users.
"So, we are always looking for other points in the prostaglandin -- aromatase -- estrogen pathway that can shield women from breast cancer without raising risks in other areas," Dr. Dannenberg says.
That's one of the reasons the results of the new study are intriguing. Using experiments conducted in cell culture and in the mammary tissues of mice, the Weill Cornell team discovered that two cellular receptors -- EP2 and EP4 -- switch on a complex biochemical pathway that activates the aromatase gene.
"It appears that PGE2 binds to these receptors and that this causes a downregulation of BRCA1," Dr. Subbaramaiah says. "As we already know, less BRCA1 means more aromatase activity to produce estrogen, and that could mean a higher risk for estrogen-receptor positive cancer."
The team found that EP2 and EP4 performed in this way in both adipocytes (fat cells) and in breast cancer cells. This could be important for both the development and growth of breast cancer.
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| Contact: Andrew Klein ank2017@med.cornell.edu 212-821-0560 New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College Source:Eurekalert |
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