Featured Research

from universities, journals, and other organizations

An Early Warning System For Dangerous Breast Cancer?

April 12, 2002
University Of Michigan Health System
A tiny protein called RhoC found in breast tumors may someday give doctors and patients an early warning system that could spot dangerously aggressive breast cancer long before it begins to spread, and identify the need for aggressive treatment.

SAN FRANCISCO, CA — A tiny protein called RhoC found in breast tumors may someday give doctors and patients an early warning system that could spot dangerously aggressive breast cancer long before it begins to spread, and identify the need for aggressive treatment.

Related Articles

A test to detect the protein is still more than a year away from clinical trials. But promising early results show that RhoC can serve as a marker for breast tumors that are most likely to spread, or metastasize — even identifying them when they’re less than a centimeter in diameter.

Physicians from the University of Michigan Comprehensive Cancer Center developed the test based on their prior research on the RhoC gene, and proved its effectiveness in 182 tissue samples from the U-M’s breast cancer library. Results will be presented April 9 at the meeting of the American Association for Cancer Research.

The test detected invasive cancer that had the potential to metastasize with 88 percent specificity, and had 92 percent specificity for tiny tumors that had already metastasized. Samples of normal breast, benign breast cysts, or non-invasive breast cancer had little RhoC.

“This is a very promising marker for small but invasive breast cancers that may metastasize, which right now are hard to identify,” says lead author Celina Kleer, M.D., an assistant professor of pathology at the U-M Medical School who specializes in breast cancer. “While more research is needed before clinical testing can begin, we hope it will help identify early-stage cancer that could be vulnerable to aggressive treatment, perhaps with drugs that target Rho protein.”

Kleer and her colleagues, including experienced RhoC researchers Sofia Merajver, M.D., Ph.D., associate professor of internal medicine, and Kenneth van Golen, Ph.D., assistant professor, embarked on the study to find out how much RhoC was produced in different kinds of breast cancer cells, compared with normal breast cells.

Previously, they had shown that the RhoC gene was overexpressed in inflammatory breast cancer, a particularly deadly variety that grows and metastasizes quickly. Overexpression of the gene, they believed, might also occur in other kinds of aggressive breast cancer – leading to larger quantities of the RhoC protein in cells of those cancers.

RhoC, whose full name is RhoC-GTPase, is an enzyme involved in changing the internal skeleton of a cell — changes that allow a cell to polarize or move. That ability is important in muscle cells, which produce a lot of RhoC. But in cancerous non-muscle cells, RhoC is key to the structural changes that give a cell the ability to break off from a tumor, float through the body in the bloodstream, and take hold in a satellite location – in other words, to metastasize.

In finding the inflammatory breast cancer correlation, the U-M team was the first to show that RhoC, already implicated in liver, pancreas and skin cancer, was also involved in breast cancer. U-M researchers, led by Merajver, then showed that transplanting the RhoC gene into normal breast cells in mice transforms those cells into cancerous ones with metastatic potential.

The new research started with the development of a RhoC test. With help from the U-M Protein Structure Facility, and their knowledge of the RhoC gene, the team created an antibody that would latch on to RhoC protein anywhere in a tissue sample. A stain specific to the antibody then allowed the U-M researchers to see how concentrated the protein was in different tissue samples from breast tumors and surrounding areas.

The breast cancer library at the Cancer Center provided 182 tissue samples from 164 patients whose breasts had been biopsied at the U-M, as well as information about whether they had cancer or benign breast disease like fibrocystic changes. Samples of breast cancer tissue were accompanied by information describing exactly what variety of cancer it was, how large the tumor was, whether it was invasive (spreading beyond the layer of cells where it started and into healthy tissue), what stage it was in, and whether it had metastasized through the body.

The cancerous samples included everything from ductal carcinoma in situ (a low-grade localized condition), to stage IV invasive ductal carcinomas that had spread to lymph nodes or other parts of the body. The wide spectrum allowed the team to look for differences between cancers of different sizes, stages, types and levels of invasiveness.

Antibody staining revealed the expected high levels of RhoC in muscle and blood vessel cells surrounding the breast tissue, and none in normal breast tissue. But the concentrations of the reddish-brown stain in the cancerous tissue varied greatly. When Kleer correlated the samples that stained darkest with their clinical characteristics, she discovered a connection.

“We found RhoC only in invasive cancers, and it almost always correlated with the presence of metastases. Very few non-metastatic cancers contained high levels of RhoC,” she says. “The level of RhoC expression also increased as the stage of the breast cancer increased, which is another confirmation that it’s a marker of more aggressive cancer. We had enough samples from invasive metastatic cancers of less than one centimeter in size to show that RhoC is highly specific for those tumors, but we’d like to look at more samples to be sure.”

Kleer, Merajver, van Golen and their colleagues are preparing to examine even more breast samples for the presence of RhoC, to see if their initial results hold up. The team is also in the process of planning clinical studies on the predictive power of RhoC.

The study was funded by the National Institutes of Health, the Department of Defense’s breast cancer research program, and a grant from the John and Suzanne Munn Endowment at the U-M Comprehensive Cancer Center. In addition to Kleer, Merajver, and van Golen, the study’s authors are Zhi-Fen Wu, M.D.; Yanhong Zhang, Ph.D.; and Mark Rubin, M.D.

Story Source:

The above story is based on materials provided by University Of Michigan Health System. Note: Materials may be edited for content and length.

Cite This Page:

University Of Michigan Health System. "An Early Warning System For Dangerous Breast Cancer?." ScienceDaily. ScienceDaily, 12 April 2002. <www.sciencedaily.com/releases/2002/04/020411072646.htm>.
University Of Michigan Health System. (2002, April 12). An Early Warning System For Dangerous Breast Cancer?. ScienceDaily. Retrieved January 28, 2015 from www.sciencedaily.com/releases/2002/04/020411072646.htm
University Of Michigan Health System. "An Early Warning System For Dangerous Breast Cancer?." ScienceDaily. www.sciencedaily.com/releases/2002/04/020411072646.htm (accessed January 28, 2015).

Share This

More From ScienceDaily

More Health & Medicine News

Wednesday, January 28, 2015

Featured Research

from universities, journals, and other organizations

Featured Videos

from AP, Reuters, AFP, and other news services

Poultry Culled in Taiwan to Thwart Bird Flu

Poultry Culled in Taiwan to Thwart Bird Flu

Reuters - News Video Online (Jan. 28, 2015) Taiwan culls over a million poultry in efforts to halt various strains of avian flu. Julie Noce reports. Video provided by Reuters
Powered by NewsLook.com
Shark Bite Victim Making Amazing Recovery

Shark Bite Victim Making Amazing Recovery

AP (Jan. 27, 2015) A Texas woman who lost more than five pounds of flesh to a shark in the Bahamas earlier this month could be released from a Florida hospital soon. Experts believe she was bitten by a bull shark while snorkeling. (Jan. 27) Video provided by AP
Powered by NewsLook.com
Shoveling Snow: How to Prevent Back Injuries

Shoveling Snow: How to Prevent Back Injuries

Washington Post (Jan. 26, 2015) What&apos;s the proper technique for shoveling snow? A physical therapist offers specific tips for protecting your back while you dig out this winter. Video provided by Washington Post
Powered by NewsLook.com
Ebola Mistakes Should Serve a Lesson Says WHO

Ebola Mistakes Should Serve a Lesson Says WHO

AFP (Jan. 25, 2015) The World Health Organization&apos;s chief on Sunday admitted the UN agency had been caught napping on Ebola, saying it should serve a lesson to avoid similar mistakes in future. Duration: 00:55 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.


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


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