Featured Research

from universities, journals, and other organizations

Researchers Zero In On Estrogen's Role In Breast-cancer Cell Growth

Date:
September 9, 2005
Source:
University of Illinois at Urbana-Champaign
Summary:
Why do estrogen-dependent breast-cancer cells grow and spread rapidly? Researchers at the University of Illinois at Urbana-Champaign say it may be because estrogen virtually eliminates levels of a vitally important regulatory protein.

Jonna Frasor, a postdoctoral researcher, left, and Benita S. Katzenellenbogen, a Swanlund Professor of Cell and Developmental Biology, report that human breast-cancer cells exposed to estrogen in their laboratory showed a dramatic reduction in numbers of a crucial nuclear receptor corepressor, a protein known as N-CoR.
Credit: Photo by Kwame Ross

CHAMPAIGN, Ill. -- Why do estrogen-dependent breast-cancer cells grow and spread rapidly? Researchers at the University of Illinois at Urbana-Champaign say it may be because estrogen virtually eliminates levels of a vitally important regulatory protein.

In a paper that will appear in the Sept. 13 issue of the Proceedings of the National Academy of Sciences, the scientists report that human breast-cancer cells exposed to estrogen in their laboratory showed a dramatic reduction in numbers of a crucial nuclear receptor corepressor, a protein known as N-CoR (pronounced "en CORE"). They also found that the anti-estrogen drug tamoxifen, often used in breast-cancer treatments, encouraged N-CoR recovery, a beneficial activity. The paper was published online last week.

"Because estrogen has the ability to reduce the levels of N-CoR, estrogen then can promote the proliferation and progression of breast cancer, because the balance of co-activators and co-repressors involved in normal gene transcription is altered," said Benita S. Katzenellenbogen, a Swanlund Professor of Cell and Developmental Biology at Illinois. She also is a professor of molecular and integrative physiology.

The findings may have sweeping implications, said Katzenellenbogen and lead author Jonna Frasor, a postdoctoral researcher who joins the faculty of the department of physiology and biophysics in the U. of I. College of Medicine at Chicago this month.

For one, the mechanisms at play could explain at least some of the mixed results seen in women using estrogen and progesterone in hormone therapy, said Katzenellenbogen, who also is a professor in the U. of I. College of Medicine at Urbana-Champaign.

While numbers of N-CoR proteins fell to 20 percent of normal, the level of N-CoR's messenger RNA went untouched. The reduction of N-CoR followed an up regulation of the ubiquitin ligase Siah2, an enzyme that targets certain proteins for degradation, Frasor said.

"Here we had an effect on the level of the N-CoR protein without affecting the level of N-CoR mRNA," Katzenellenbogen said. "This is the result of the initial effect of estrogen on gene expression, which was to up regulate the mRNA levels for a ubiquitin ligase. So by changing the level of this ligase, it had a dramatic effect on the level of N-CoR protein without affecting gene expression for N-CoR itself."

This "secondary effect" may have broad implications for other important cellular activities, the researchers theorize. Reductions in N-CoR over time also could promote cancer development in other sites, such as the uterus, and could adversely affect the desired activities of vitamin D, retinoid and thyroid receptors, Katzenellenbogen said.

The study sheds light on the impact of estrogen on certain cells, as well as how tamoxifen works as an anti-estrogen to facilitate recovery of N-CoR, she and Frasor said.

"Eventually," Katzenellenbogen said, "understanding more of the mechanisms involved could lead to the development of other related agents that might reduce some of the unwanted side effects of tamoxifen, such as stimulation of the uterus."

In addition to Katzenellenbogen and Frasor, Jeanne M. Danes, a researcher in the department of molecular and integrative physiology, and doctoral student Cory C. Funk were co-authors of the study.

###

The National Institutes of Health and the Breast Cancer Research Foundation funded the research.


Story Source:

The above story is based on materials provided by University of Illinois at Urbana-Champaign. Note: Materials may be edited for content and length.


Cite This Page:

University of Illinois at Urbana-Champaign. "Researchers Zero In On Estrogen's Role In Breast-cancer Cell Growth." ScienceDaily. ScienceDaily, 9 September 2005. <www.sciencedaily.com/releases/2005/09/050909074901.htm>.
University of Illinois at Urbana-Champaign. (2005, September 9). Researchers Zero In On Estrogen's Role In Breast-cancer Cell Growth. ScienceDaily. Retrieved April 20, 2014 from www.sciencedaily.com/releases/2005/09/050909074901.htm
University of Illinois at Urbana-Champaign. "Researchers Zero In On Estrogen's Role In Breast-cancer Cell Growth." ScienceDaily. www.sciencedaily.com/releases/2005/09/050909074901.htm (accessed April 20, 2014).

Share This



More Health & Medicine News

Sunday, April 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Nine-Month-Old Baby Can't Open His Mouth

Nine-Month-Old Baby Can't Open His Mouth

Newsy (Apr. 19, 2014) Nine-month-old Wyatt Scott was born with a rare disorder called congenital trismus, which prevents him from opening his mouth. Video provided by Newsy
Powered by NewsLook.com
'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
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