Featured Research

from universities, journals, and other organizations

Study Pinpoints Mechanism Behind Tamoxifen Side Effect

Date:
March 29, 2002
Source:
Dana-Farber Cancer Institute
Summary:
Researchers at Dana-Farber Cancer Institute have identified the underlying mechanism that causes one of the unwanted side effects of tamoxifen. The study, published in the March 29 issue of Science, may help researchers home in on new medications that, like tamoxifen, reduce the risk of certain types of breast cancer, but do not carry tamoxifen’s potentially dangerous downside.

BOSTON – Researchers at Dana-Farber Cancer Institute have identified the underlying mechanism that causes one of the unwanted side effects of tamoxifen. The study, published in the March 29 issue of Science, may help researchers home in on new medications that, like tamoxifen, reduce the risk of certain types of breast cancer, but do not carry tamoxifen’s potentially dangerous downside.

Related Articles


“Tamoxifen was the first drug shown capable of reducing the chances of breast cancer development in some women at risk for the disease,” says Myles Brown, MD, Dana-Farber researcher and the study’s senior author. “But many women have been reluctant to take it because of potential side effects. By understanding the basic mechanism by which the drug works, we can look for medications whose profile of effects is more advantageous to patients.”

Tamoxifen is currently used to lower the risk of breast cancer recurrence in women whose breast cell growth is fueled by the hormone estrogen. In the breast, tamoxifen acts as an anti-estrogen, blocking the hormone from latching onto cells and delivering a growth signal. In some other parts of the body, however, tamoxifen and estrogen have similar effects: both substances help strengthen women’s bones, for example, and may help keep their cardiovascular systems healthy.

Unfortunately, estrogen and tamoxifen also have a common detrimental effect – a heightened risk of the development of endometrial cancer. A nationwide study is under way to determine whether a drug called raloxifene, which may reduce breast cancer risk without raising the risk of endometrial cancer, prevents breast cancer as effectively as tamoxifen does.

Both tamoxifen and raloxifene belong to a class of substances known as selective estrogen receptor modulators, or SERMs, which bind inside cells at the same receptors that estrogen does. In some types of cells, such as those in bones and the cardiovascular system, the effects of this binding are similar for estrogen and tamoxifen. In breast cells, however, a coupling with estrogen spurs cell growth – increasing the chances they’ll become cancerous – whereas a coupling with tamoxifen or raloxifene restrains their growth. In uterine cells, estrogen and tamoxifen have the same growth-promoting effect, whereas raloxifene does not.

The challenge for scientists has been to understand and explain these differences. Knowing why tamoxifen and raloxifene behave like estrogen in some cells but not in others may help researchers “fine-tune” SERMs so they provide the benefits of current drugs without the shortcomings.

Eight years ago, Brown and his associates proposed that the reason for the differences lay in other proteins that bind to the estrogen receptor once estrogen or a SERM is nestled there. Brown’s team theorized that some of these proteins, known as co-regulators, turn on genes that initiate cell division, while others restrain it. If more activators than repressors are attracted to the estrogen receptors, growth is stimulated; if more repressors than activators, growth is restrained.

The new study offers convincing evidence that the theory is right. Brown and Yongfeng Shang, PhD, the paper’s lead author and an instructor in medicine at the Dana-Farber and Harvard Medical School, found that in breast cells, both tamoxifen and raloxifene draw repressor proteins to the estrogen receptors. In endometrial cells, tamoxifen, but not raloxifene, acts like estrogen by luring activating proteins to the site, potentially sparking the excessive growth associated with cancer.

“Our findings demonstrate that the make-up of the co-regulating proteins present in a cell determines how it will respond to treatment with different SERMs,” states Brown, who is also an associate professor of medicine at Harvard Medical School. “This knowledge will help us better predict the range of effects of newly developed SERMs, and study those that are likely to have the best spectrum of benefits.”

###The research was supported by the National Cancer Institute and the Department of Defense Breast Cancer Research Program.

Dana-Farber Cancer Institute (http://www.danafarber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Cite This Page:

Dana-Farber Cancer Institute. "Study Pinpoints Mechanism Behind Tamoxifen Side Effect." ScienceDaily. ScienceDaily, 29 March 2002. <www.sciencedaily.com/releases/2002/03/020329072214.htm>.
Dana-Farber Cancer Institute. (2002, March 29). Study Pinpoints Mechanism Behind Tamoxifen Side Effect. ScienceDaily. Retrieved October 26, 2014 from www.sciencedaily.com/releases/2002/03/020329072214.htm
Dana-Farber Cancer Institute. "Study Pinpoints Mechanism Behind Tamoxifen Side Effect." ScienceDaily. www.sciencedaily.com/releases/2002/03/020329072214.htm (accessed October 26, 2014).

Share This



More Health & Medicine News

Sunday, October 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Nurse Nina Pham Cured of Ebola

Texas Nurse Nina Pham Cured of Ebola

AFP (Oct. 25, 2014) — An American nurse who contracted Ebola while caring for a Liberian patient in Texas has been declared free of the virus and will leave the hospital. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
Toxin-Packed Stem Cells Used To Kill Cancer

Toxin-Packed Stem Cells Used To Kill Cancer

Newsy (Oct. 25, 2014) — A Harvard University Research Team created genetically engineered stem cells that are able to kill cancer cells, while leaving other cells unharmed. Video provided by Newsy
Powered by NewsLook.com
IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins