Featured Research

from universities, journals, and other organizations

How Tamoxifen Stimulates Uterine Cell Growth And Cancer

Date:
July 14, 2009
Source:
University of California - San Francisco
Summary:
Researchers have identified a new "feed-forward" pathway linking estrogen receptors in the membrane of the uterus to a process that increases local estrogen levels and promotes cell growth.

UCSF researchers have identified a new "feed-forward" pathway linking estrogen receptors in the membrane of the uterus to a process that increases local estrogen levels and promotes cell growth.

The research is significant in helping determine why tamoxifen and other synthetic estrogens are linked to increased rates of endometriosis and uterine cancer, and identifies a pathway that could be targeted in drug therapies for those diseases, researchers say.

Findings are published in the July 1, 2009 issue of Cancer Research, the journal of the American Association for Cancer Research.

The research found that when activated by estrogens, endometrial cells obtained from patients suffering from endometriosis or human uterine cancer cells initiate a previously unknown cascade of signals that leads to cellular replication and further estrogen production, the paper says.

The ensuing cycle leads to abnormal growth of the cells lining the uterus, or endometrium, which occurs in endometriosis and uterine cancer, according to senior author Holly A. Ingraham, PhD, a professor in the UCSF School of Medicine's Department of Cellular and Molecular Pharmacology.

"It turns out that displaced endometrial cells, such as those used in this study, are estrogen factories," said Ingraham, who also is affiliated with the UCSF Helen Diller Family Comprehensive Cancer Center and the UCSF Center for Reproductive Sciences. "They pump out estrogen in a feed-forward pathway, so the more estrogen they produce, the more estrogen they're capable of producing."

While this pathway was previously unknown, Ingraham said a June 2009 paper led by researchers at the University of New Mexico and published in the journal "Nature Chemical Biology" showed that blocking the GPR30 receptor in this pathway decreases uterine proliferation in a mouse. The two together, she said, validate what researchers now think may be a key area in addressing both uterine cancer and endometriosis.

Uterine cancer is the fourth most common cancer in women, with more than 37,000 women being diagnosed each year in the United States alone, according to data from the Centers for Disease Control.

Endometriosis, in which endometrial cells grow in areas other than the uterus, is the most common gynecological disease and affects more than 5.5 million women in North America, according to the National Institutes of Health. The disease often causes severe pain and can lead to infertility.

Working in collaboration with clinicians at Northwestern University in Chicago, the UCSF team analyzed cells from women with ectopic endometriosis. By studying those patients' endometrial cells, the team was able to identify an unusual, circular pathway involving these cells, the transmembrane estrogen receptor GPR30 and the nuclear receptor SF-1.

The researchers propose that this pathway increases local concentrations of estrogen and, together with classic estrogen-receptor signaling, control the proliferative effects of these estrogens in promoting endometriosis and endometrial cancers.

The UCSF team used a unique chemical biology approach, making use of a tamoxifen-like compound developed in the laboratory of co-author Thomas Scanlan, PhD, who is affiliated with both the UCSF Department of Pharmaceutical Chemistry and the Department of Chemical Biology at the Oregon Health Sciences University in Portland.

"Tamoxifen and other synthetic estrogens have been known to increase the risk of uterine cancer, but until now, we didn't know why that was on a cellular level," Ingraham said. "We think this pathway is going to be an important one in solving that mystery."

The lead investigator on the paper was Benjamin C. Lin. Lin and co-author Sandra C. Tobias are affiliated with the Department of Pharmaceutical Chemistry at UCSF. Other co-authors are Miyuki Suzawa, in the UCSF Department of Cellular and Molecular Pharmacology; Raymond D. Blind in the UCSF Department of Pharmaceutical Chemistry and Department of Cellular and Molecular Pharmacology; and Serdar E. Bulun, in the Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University.

The authors report no potential conflicts of interest in this research.


Story Source:

The above story is based on materials provided by University of California - San Francisco. Note: Materials may be edited for content and length.


Journal Reference:

  1. Benjamin C. Lin et al. Stimulating the GPR30 Estrogen Receptor with a Novel Tamoxifen Analogue Activates SF-1 and Promotes Endometrial Cell Proliferation. Cancer Research, 69, 5415, July 1, 2009 DOI: 10.1158/0008-5472.CAN-08-1622

Cite This Page:

University of California - San Francisco. "How Tamoxifen Stimulates Uterine Cell Growth And Cancer." ScienceDaily. ScienceDaily, 14 July 2009. <www.sciencedaily.com/releases/2009/07/090702170211.htm>.
University of California - San Francisco. (2009, July 14). How Tamoxifen Stimulates Uterine Cell Growth And Cancer. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2009/07/090702170211.htm
University of California - San Francisco. "How Tamoxifen Stimulates Uterine Cell Growth And Cancer." ScienceDaily. www.sciencedaily.com/releases/2009/07/090702170211.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. Video provided by Newsy
Powered by NewsLook.com
We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 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:
from the past week

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