Featured Research

from universities, journals, and other organizations

Study finds new points of attack on breast cancers not fueled by estrogen

Date:
July 29, 2011
Source:
Dana-Farber Cancer Institute
Summary:
Although it sounds like a case of gender confusion on a molecular scale, the male hormone androgen spurs the growth of some breast tumors in women. In a new study, scientists provide the first details of the cancer cell machinery that carries out the hormone's relentless growth orders.

Although it sounds like a case of gender confusion on a molecular scale, the male hormone androgen spurs the growth of some breast tumors in women. In a new study, scientists at Dana-Farber Cancer Institute provide the first details of the cancer cell machinery that carries out the hormone's relentless growth orders.

The study, published the journal Cancer Cell on July 12, provides scientists with several inviting targets -- cell proteins that snap into action in response to androgen -- for future therapies. Drugs that block those proteins could slow or stifle tumor growth in many breast cancer patients who are not helped by standard hormone-blocking agents such as tamoxifen.

"We identified a novel subtype of breast tumor which grows in response to androgen but not estrogen, and have uncovered the signaling pathways involved in its growth," says senior author Myles Brown, MD. "And we've demonstrated that drugs capable of blocking these pathways, including the receptor for androgen itself, can inhibit tumor growth. This opens new avenues to the treatment of some women with breast cancer that doesn't respond to standard endocrine therapies."

About 70-75 percent of breast tumors are fueled by the female hormone estrogen. Their cells are loaded with estrogen receptors (ER), trap-like structures specially shaped to ensnare estrogen molecules. When estrogen becomes lodged in an estrogen receptor, it sets off a chain of events that prompts the cell to grow and proliferate. Drugs such as tamoxifen block estrogen from entering the receptor, thereby thwarting the growth process.

The remaining 25-30 percent of breast cancers, dubbed ER-negative tumors, lack estrogen receptors, and thus do not respond to tamoxifen and similar agents. Scientists know that the majority of breast tumors -- even those with estrogen receptors -- have receptors for androgen, but the reasons for these receptors' presence, and how they might influence tumor growth, have been unknown.

It might seem odd that some women's breast cancers carry receptors for a hormone associated with males, but androgen is also involved in the normal development of secondary sexual characteristics in females, Brown remarks. Scientists have theorized that androgen propels the growth of breast cancer cells that have receptors for androgen but not for estrogen. The current study set out to find if that is the case and, if so, why.

Using published data on the genomic make-up of breast tumor cells, Brown and his colleagues found a distinctive group -- accounting for five to 10 percent of all breast cancer patients -- that had large numbers of androgen receptors, no ERs, and an oversupply of a protein called HER2. Cells of this type proliferated rapidly when exposed to androgen.

To understand the mechanism behind this growth, investigators did a mass screening of these tumor cells' genetic material to see which sections of DNA bind to the androgen receptor -- an indication of which genes the receptor directly switches on and off. By combining these findings with a survey of all the genes active within these cells, the researchers found that the androgen receptor governs two "transmission lines" -- or pathways -- for growth signals. The pathways, named for important proteins within them (WNT and HER2), play central roles in cell division and proliferation.

When researchers used drugs to handcuff the androgen receptor or the WNT or HER2 proteins in ER-negative breast cancer cells, tumor growth slowed -- both in laboratory cell cultures and in mice grafted with the cells.

"These findings are strong evidence that therapies that shut down proteins in the WNT or HER2 pathways, or block the androgen receptor itself, can be effective anti-tumor agents for women with this variety of breast cancer," Brown says. "Combination therapies that target proteins at different points in the pathways are likely to have the greatest success."

The study involved a close collaboration between Brown's lab and the computation biology group at Dana-Farber headed by Shirley Liu, PhD. Brown and Liu recently founded the Dana-Farber Center for Functional Cancer Epigenetics in order to make the genomic and computational approaches used in this study more widely available to the scientific community.

The co-first authors of the study are Min Ni, PhD, and Yiwen Chen, PhD, of Dana-Farber. Co-authors include Elgene Lim, MD, PhD, Shannon Bailey, PhD, and Yuuki Imai, MD, PhD, of Dana-Farber; and Hallie Wimberly and David Rimm, MD, PhD, of Yale University School of Medicine.

The study was supported by grants from the National Cancer Institute, National Institutes of Health, and Department of Defense.


Story Source:

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


Journal Reference:

  1. Min Ni, Yiwen Chen, Elgene Lim, Hallie Wimberly, Shannon T. Bailey, Yuuki Imai, David L. Rimm, X. Shirley Liu, Myles Brown. Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer. Cancer Cell, 2011; 20 (1): 119-131 DOI: 10.1016/j.ccr.2011.05.026

Cite This Page:

Dana-Farber Cancer Institute. "Study finds new points of attack on breast cancers not fueled by estrogen." ScienceDaily. ScienceDaily, 29 July 2011. <www.sciencedaily.com/releases/2011/07/110711131324.htm>.
Dana-Farber Cancer Institute. (2011, July 29). Study finds new points of attack on breast cancers not fueled by estrogen. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2011/07/110711131324.htm
Dana-Farber Cancer Institute. "Study finds new points of attack on breast cancers not fueled by estrogen." ScienceDaily. www.sciencedaily.com/releases/2011/07/110711131324.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

House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Despite Health Questions, E-Cigs Are Beneficial: Study

Despite Health Questions, E-Cigs Are Beneficial: Study

Newsy (July 31, 2014) Citing 81 previous studies, new research out of London suggests the benefits of smoking e-cigarettes instead of regular ones outweighs the risks. Video provided by Newsy
Powered by NewsLook.com
Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
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