Featured Research

from universities, journals, and other organizations

Study Uncovers 'Significant' Functional Differences Of Novel Estrogen Receptor

Date:
June 9, 2006
Source:
Scripps Research Institute
Summary:
Researchers have discovered a novel variant of a known human estrogen receptor. The new variant "functions very differently" in response to estrogen signaling, the study said, inhibiting key estrogen-dependent and estrogen-independent activities and stimulating cell growth. Because of these differences, this new estrogen receptor could become an important therapeutic target and may play a further signaling role in other estrogen target tissues, including uterus and prostate tissues.

Scientists at The Scripps Research Institute, working in collaboration with researchers from Creighton University and the Medical College of Zhejiang University (P.R. China), have discovered a novel variant of a known human estrogen receptor (hER-a66). The new variant -- called hER-a36 -- "functions very differently" from hER-a66 in response to estrogen signaling, the study said, inhibiting key estrogen-dependent and estrogen-independent activities of hER-a66 and stimulating cell growth.

Because of these differences, this new estrogen receptor could become an important therapeutic target and may play a further signaling role in other estrogen target tissues, including uterus and prostate tissues.

These new findings could significantly advance the understanding of the effects of estrogen in breast cancer and point the way towards new and potentially more effective treatments of the disease.

The new study was published this week in an advanced online edition of the Proceedings of the National Academy of Sciences.

Estrogen has long been linked to the development of breast cancer, both through the stimulation of breast cell growth, which can lead to mutation, and through estrogen metabolism, which can interfere with apoptosis and DNA repair. Estrogen receptors mediate the majority of the actions of estrogen, including the metastatic growth of breast cancer cells, and are an important marker in therapy; readable levels of estrogen receptor proteins are expressed in a large portion of human breast cells.

Professor Thomas F. Deuel, M.D., a Scripps Research scientist who participated in the study said, "The estrogen and anti-estrogen signaling pathways mediated by this new receptor could explain why some breast cancers grow worse or become resistant to anti-estrogen therapy, specifically the drug tamoxifen, which blocks estrogen signaled responses through ER-a66 in breast tissue." According to the National Cancer Institute, anti-estrogen therapy is most often used in postmenopausal women whose tumors grow in response to the hormone.

"Worldwide, breast cancer is the most common form of cancer in women and the second most common cause of death for women in the United States," Deuel said. "The toll in suffering and mortality is especially devastating because breast cancer strikes women at a time in their lives when they are most productive and they are busy with children and raising a family. This continues despite great progress in the diagnosis and development of treatment strategies in human breast cancer. Our new study may help in finding a solution to remaining critical questions surrounding the mechanisms that drive breast cancer."

Earlier research into how hormones signal various functions in hormone-responsive tissues led to the identification of the human estrogen receptor (hER), which is mediated by specific nuclear receptors including hER-a66. However, questions regarding the functional significance of cell plasma membrane-initiated estrogen signaling in human breast cancer and in other estrogen responsive tissues remain largely unanswered.

The significance of a cell plasma membrane-based estrogen receptor that triggers estrogen signaling has been a point of controversy for a long time, the researchers said. The study showed that hER-a36, unlike other estrogen receptors, is predominantly localized on the cell plasma membrane that surrounds the cell cytoplasm; the receptor stimulates cell growth by estrogens and anti-estrogens through activation of the MAPK/ERK signaling pathway-a pathway that is involved in cell differentiation and growth. According to the study, this new finding could lead to the potentially "critically important conclusion" that estrogens and anti-estrogens can both stimulate cell proliferation through membrane-associated hER-a36.

"By identifying and cloning a novel form of the human estrogen receptor, our studies suggest that hER-a36 may have a greater potential to signal estrogen stimulated membrane responses than hER-a66," Deuel said. "The results of our experiments demonstrate that the presence of hER-a36 strikingly inhibits both estrogen-dependent and estrogen-independent transactivation functions-which result in protein production-mediated by ER-a66."

The researchers expressed surprise that anti-estrogen treatments such as tamoxifen stimulate cell growth and that the anti-estrogens appear to have a stronger and a more prolonged activation of the MAPK/ERK signaling pathway than the estrogens tested.

These findings, the study said, support the conclusion that tamoxifen functions as both agonist and antagonist of estrogen signaling and that the expression of hER-a36 may be involved in the development of tamoxifen-resistant human breast cancer. This raises the possibility that estrogen-activated ER-a36 signaling initiated in the cell plasma membrane may actually accelerate the course of tamoxifen-resistant human breast cancer.

"The apparent ability of hER-a36 to trigger membrane-initiated estrogen and anti-estrogen signaling that leads to cell growth makes it an important new member of the estrogen signaling pathway," Deuel said. "Its potential to antagonize estrogen-stimulated transactivational functions transduced by hERa66 is also an important feature of the new receptor’s functional responses to estrogens. Based on our new findings, further studies of this potentially very important protein are likely to significantly advance our understanding of the diverse physiological and pathological effects of estrogen action."

Other authors of the study include ZhaoYi Wang, XinTian Zhang, Brian W. Loggie of Creighton University; Peng Shen (Zhejiang University PR China); and Yunchao Chang of Scripps Research.

This work was supported by the National Institutes of Health and the Nebraska Tobacco Settlement Biomedical Research program.


Story Source:

The above story is based on materials provided by Scripps Research Institute. Note: Materials may be edited for content and length.


Cite This Page:

Scripps Research Institute. "Study Uncovers 'Significant' Functional Differences Of Novel Estrogen Receptor." ScienceDaily. ScienceDaily, 9 June 2006. <www.sciencedaily.com/releases/2006/06/060609092018.htm>.
Scripps Research Institute. (2006, June 9). Study Uncovers 'Significant' Functional Differences Of Novel Estrogen Receptor. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2006/06/060609092018.htm
Scripps Research Institute. "Study Uncovers 'Significant' Functional Differences Of Novel Estrogen Receptor." ScienceDaily. www.sciencedaily.com/releases/2006/06/060609092018.htm (accessed August 1, 2014).

Share This




More Health & Medicine News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Quintuplets Head Home

Texas Quintuplets Head Home

Reuters - US Online Video (Aug. 1, 2014) After four months in the hospital, the first quintuplets to be born at Baylor University Medical Center head home. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Patient Coming to U.S. for Treatment

Ebola Patient Coming to U.S. for Treatment

Reuters - US Online Video (Aug. 1, 2014) A U.S. aid worker infected with Ebola while working in West Africa will be treated in a high security ward at Emory University in Atlanta. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Vaccine Might Be Coming, But Where's It Been?

Ebola Vaccine Might Be Coming, But Where's It Been?

Newsy (Aug. 1, 2014) Health officials are working to fast-track a vaccine — the West-African Ebola outbreak has killed more than 700. But why didn't we already have one? Video provided by Newsy
Powered by NewsLook.com
Study Links Certain Birth Control Pills To Breast Cancer

Study Links Certain Birth Control Pills To Breast Cancer

Newsy (Aug. 1, 2014) Previous studies have made the link between birth control and breast cancer, but the latest makes the link to high-estrogen oral contraceptives. 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