Navigation Links
Weill Cornell team identifies potential new drug targets against hormone-dependent breast cancer
Date:2/28/2008

NEW YORK (Feb. 27, 2008) -- The identification of two cellular receptors that likely contribute to the genesis of hormone-dependent breast cancer points the way to new, highly targeted therapies against the disease, says a team led by scientists at Weill Cornell Medical College in New York City.

The finding also helps explain how daily use of medicines such as aspirin might help keep these breast tumors at bay.

"These two receptors, called EP2 and EP4, form key links in a biochemical pathway that boosts estrogen production in fat and breast cancer cells -- this, in turn, may increase a woman's risk for developing hormone receptor-positive breast cancer. Finding ways to interrupt this pathway in a manner that causes few side effects is the ultimate goal of this research," explains the study's senior author Dr. Andrew Dannenberg, director of the newly established Cancer Center at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, and the Henry R. Erle, M.D.Roberts Family Professor of Medicine at Weill Cornell Medical College.

The new findings were published recently in the online edition of the Journal of Biological Chemistry.

About 75 percent of all breast malignancies are "estrogen receptor-positive," meaning that their cells carry receptors attuned to estrogen. In the presence of the hormone, these cancer cells will divide and grow. For this reason, anti-estrogen drugs such as tamoxifen and aromatase inhibitors have come to the forefront in the fight against hormone-dependent breast cancer.

"Aromatase, an enzyme, boosts the amount of estrogen made by both fat cells and breast cancer cells," explains the study's lead author, Dr. Kotha Subbaramaiah, recently appointed the Jack Fishman Associate Professor of Cancer Prevention at Weill Cornell. "Cancer researchers have for years been exploring the pathway by which aromatase is regulated. We know that if you reduce aromatase activity that you also reduce levels 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.

"We also validated the presence of this pathway in an animal model, the first time that's ever been done," Dr. Dannenberg notes.

The finding has many implications going forward. First of all, it adds valuable new information to the study of hormone-dependent breast cancer generally. "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," Dr. Dannenberg says.

Finally, the receptors offer brand new targets for pharmaceutical research. "In fact, drugs that work against EP2 and EP4 ('antagonists') are already in development by pharmaceutical companies," Dr. Subbaramaiah says. "Our confirmation of the receptors' key role in regulating aromatase activity supports the further development of this form of targeted therapy."


'/>"/>

Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

Related medicine news :

1. NIH selects Weill Cornell Medical College to lead new NYC translational research collaboration
2. The latest about male infertility and testosterone from NewYork-Presbyterian/Weill Cornell
3. White House awards Weill Cornells Bruce McCandliss highest honor for early career scientists
4. Weill Cornell receives $2.4 million in grants from Gates Foundation to fight tuberculosis
5. NewYork-Presbyterian/Weill Cornell creates world-class cancer center
6. $50 million gift to NewYork-Presbyterian Hospital/Weill Cornell Medical Center
7. Healthy restaurants help make us fat, says a new Cornell study
8. By color-coding atoms, new Cornell electron microscope promises big advance in materials analysis
9. UCLA study identifies designer estrogen as potential MS drug
10. Study identifies key player in the bodys immune response to chronic stress
11. University of Iowa professor identifies new eating disorder
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/29/2016)... Village, CA (PRWEB) , ... April 29, 2016 ... ... Philadelphia Pet Expo to promote their animal line of probiotics, Petbiotics ™, ... see the large turnout of animal rescue groups networking for their non-profit organizations. ...
(Date:4/29/2016)... Wilmington, DE (PRWEB) , ... April 29, 2016 ... ... annual SMG Finance, which will be held May 16th to 18th at the ... all of the SMG managed facilities to collaborate on best practices in public ...
(Date:4/29/2016)... , ... April 29, 2016 , ... In its efforts ... Caregiver Services continues its successful franchise development and expansion as it welcomes Ferdie Vasquez ... managerial and administrative experience in his 32 years of working in various industries. ...
(Date:4/28/2016)... CITY (PRWEB) , ... April 28, 2016 , ... ... is on the world stage this week. A group of researchers and leaders ... on the Progress of Regenerative Medicine and Its Cultural Impact ” and receive ...
(Date:4/28/2016)... (PRWEB) , ... April 28, 2016 , ... University of ... McDonald to the role of vice president of Student Engagement. In addition to ... facilities, athletics and student life areas. , “In the space of just one ...
Breaking Medicine News(10 mins):
(Date:4/27/2016)... SHAWNEE, Kan. , April 27, 2016 /PRNewswire/ ... Martabano , a senior from the University of ... winner of the Bayer Excellence in Communication Award ... veterinary schools, which were awarded a total of ... Over the last four years, Bayer has provided ...
(Date:4/27/2016)... 2016 Global  urinalysis market ... by 2022, according to a new report by ... http://photos.prnewswire.com/prnh/20150105/723757 ) , Automation ... and accuracy delivered by the new generation urinalysis ... urinalysis instruments and consumables. For instance, the automatic ...
(Date:4/26/2016)... April 26, 2016 Hill-Rom Holdings, Inc. (NYSE: ... presentation at the Deutsche Bank 41 st Annual Health ... EDT. You are invited to listen to the ... or access it directly at http://edge.media-server.com/m/p/mr4uxgas . A recorded ... conclusion of the live event and accessible at the links ...
Breaking Medicine Technology: