Featured Research

from universities, journals, and other organizations

Lactation protein suppresses tumors and metastasis in breast cancer

Date:
October 24, 2012
Source:
University at Buffalo
Summary:
A protein that is necessary for lactation in mammals inhibits the critical cellular transition that is an early indicator of breast cancer and metastasis, according to new research.

A protein that is necessary for lactation in mammals inhibits the critical cellular transition that is an early indicator of breast cancer and metastasis, according to research conducted at the University at Buffalo and Princeton University and highlighted as the cover paper in November issue of Nature Cell Biology.

Related Articles


"This is the first confirmed report that this protein, called Elf5, is a tumor suppressor in breast cancer," explains Satrajit Sinha, PhD, associate professor of biochemistry in the UB School of Medicine and Biomedical Sciences and a corresponding author on the paper with Yibin Kang, PhD, in the Department of Molecular Biology at Princeton University.

The researchers say the findings provide new avenues to pursue in treating and diagnosing breast cancer and possibly cancers of other organs as well. The paper includes findings from both animal and human breast cancer models.

Under normal circumstances, Elf5 is a transcription factor that controls the genes that allow for milk production.

But when the researchers used knockout mice developed at UB, in whom Elf5 was removed, they found more than just an inability to produce milk. They found that epithelial cells in the mammary glands also became more mesenchymal, that is, more like stem cells, an early harbinger of cancer, Sinha says.

"We found that when Elf5 levels are low or absent, epithelial cells become more like stem cells, morphing into mesenchymal cells, changing their shape and appearance and migrating elsewhere in the body," says Sinha. "This is how cancer spreads."

The UB-Princeton collaboration began when lead author Rumela Chakrabarti, PhD, originally a postdoctoral researcher in Sinha's laboratory at UB, took a position in the laboratory of Yibin Kang, PhD, Warner-Lambert/Parke-Davis Professor of Molecular Biology at Princeton, whose research focus is breast cancer metastasis. This allowed Chakrabarti to harness the expertise of the two laboratories to generate such a breakthrough finding.

"Elf5 keeps normal breast cells in their current shape and restricts their movement," says Chakrabarti. She found that the protein accomplishes this by suppressing the epithelial-mesenchymal transition by directly repressing transcription of Snail2, a master regulator of mammary stem cells known to trigger the EMT.

"Elf5 keeps Snail2 repressed, but once Elf5 is lost, then there is nothing to repress Snail 2," she explains.

The paper notes that Elf5 loss is frequently detected early in the disease at the breast hyperplasia stage, when the number of cells increases. In experiments conducted by the Princeton scientists, the researchers also found that little or no Elf5 in human breast cancer samples correlated with increased morbidity.

"It seems that loss of Elf5 is an initial event in the disease, so it could also be an important diagnostic tool," Sinha notes, which is a current focus of the UB and Princeton team.

"We want to know, how early does the loss of Elf5 occur? Could we use loss of Elf5 as a reliable diagnostic tool?" he asks.

The finding reveals the complex pathways through which breast cancers develop, he says, while also providing new avenues to pursue for diagnostics and treatments.

"Our research shows that the EMT-Snail 2 pathway is a valuable one to target for early breast cancer intervention," says Sinha, "possibly by designing something to recapture the repressive effect of Elf5 or a drug that could mimic Elf5 activity. And this is just one molecule, part of a big network. That's why we are now creating a detailed map of this molecule and its associated partners in order to give us a better idea of what to look for."

Other UB co-authors on the paper are Rose-Anne Romano, PhD, research assistant professor in biochemistry, and Kirsten Smalley, research technician. Other coauthors are: Julie Hwang, Mario Andres Blanco, Martin Lukacisin and Yong Wei from Princeton; Song Liu of Roswell Park Cancer Institute; Qifeng Yang and Bruce F. Haffty of the Department of Radiation Oncology in the University of Medicine and Dentistry of New Jersey and the Cancer Institute of New Jersey; and Toni Ibrahim, Laura Mercatali and Dino Amadori of the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori in Italy.

The research was supported by the National Institutes of Health, the Department of Defense, Komen for the Cure, the Brewster Foundation and the Champalimaud Foundation.


Story Source:

The above story is based on materials provided by University at Buffalo. Note: Materials may be edited for content and length.


Journal Reference:

  1. Rumela Chakrabarti, Julie Hwang, Mario Andres Blanco, Yong Wei, Martin Lukačišin, Rose-Anne Romano, Kirsten Smalley, Song Liu, Qifeng Yang, Toni Ibrahim, Laura Mercatali, Dino Amadori, Bruce G. Haffty, Satrajit Sinha, Yibin Kang. Elf5 inhibits the epithelial–mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2. Nature Cell Biology, 2012; DOI: 10.1038/ncb2607

Cite This Page:

University at Buffalo. "Lactation protein suppresses tumors and metastasis in breast cancer." ScienceDaily. ScienceDaily, 24 October 2012. <www.sciencedaily.com/releases/2012/10/121024101531.htm>.
University at Buffalo. (2012, October 24). Lactation protein suppresses tumors and metastasis in breast cancer. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2012/10/121024101531.htm
University at Buffalo. "Lactation protein suppresses tumors and metastasis in breast cancer." ScienceDaily. www.sciencedaily.com/releases/2012/10/121024101531.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
Dads-To-Be Also Experience Hormone Changes During Pregnancy

Dads-To-Be Also Experience Hormone Changes During Pregnancy

Newsy (Dec. 18, 2014) A study from University of Michigan researchers found that expectant fathers see a decrease in testosterone as the baby's birth draws near. Video provided by Newsy
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 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