Receptors May Be Drug Targets in Hormone Dependent Breast Cancer

Aromatase (Cytochrome P450 aromatase), a product of the CYP19 gene, catalyzes the synthesis of estrogens from androgens.

Since aromatase-dependent estrogen biosynthesis has been linked to hormone-dependent breast carcinogenesis, investigators at the Weill Cornell Medical College (New York, NY, USA) set out to clarify the mechanisms that regulate CYP19 gene expression.

They reported in the February 8, 2008, online edition of the Journal of Biological Chemistry that two receptors, called EP2 and EP4, were key links in a biochemical pathway that boosted estrogen production in fat and breast cancer cells. This effect was linked to the production of the prostaglandin PGE2 through the activity of the enzyme cyclooxygenase.

"Finding ways to interrupt this pathway in a manner that causes few side effects is the ultimate goal of this research,” said senior author Dr. Andrew Dannenberg, professor of medicine at Weill Cornell Medical College. "Pinpointing the role of these receptors is like adding two important new parts to the tumor's ‘instruction kit.' You have to understand all the players involved if you hope to uncover weaknesses to fight or prevent the disease.”

The EP2 and EP4 receptors are novel targets for pharmaceutical research, and their antagonists are already in development by pharmaceutical companies.


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Weill Cornell Medical College