Scientists identify protein key to breast cancer spread, potential new drug target

Apr 09, 2007

Researchers at the Kimmel Cancer Center at Jefferson have identified a protein that they say is key to helping a quarter of all breast cancers spread. The finding, reported online the week of April 9, 2007 in the journal Proceedings of the National Academy of Sciences, could be a potential target for new drugs aimed at stopping or slowing the growth and progression of breast cancer.

Kimmel Cancer Center director Richard Pestell, M.D., Ph.D., professor and chair of cancer biology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and colleagues genetically engineered mice to lack the protein Akt1, which normally plays a role in keeping cells alive by interfering with programmed cell death. Breast and other cancers make an overabundance of the protein, and it’s thought to potentially affect survival of breast and other cancer cells as well.

To test that hypothesis, Dr. Pestell and his team bred the mice missing the gene for Akt1 with other mice that overexpressed the HER2-neu (ErbB2) oncogene, which leads to approximately 25 percent of all breast cancers. They then examined the role of Akt in the onset and progression of breast cancer in the resulting offspring.

To their surprise, mice lacking two copies of the gene that produces Akt1 rarely had any tumors. Those mice that carried only one copy of the Akt1 gene developed some tumors, but they were small and developed more slowly. Mice with two copies of Akt1 rapidly developed significant cancer.

“The finding was exciting because it told us that Akt1 is a potentially useful target for ErbB2-positive breast cancer,” Dr. Pestell says. “More interesting was that even if the mouse developed a tumor, it didn’t develop metastases. We proved that there was a requirement for Akt1 in metastasis, which makes Akt1 an exciting target for metastatic breast cancer. We knew that Akt1 could play a role in cell growth and size, but the idea that it could play a role in migration and metastasis was an unexpected new finding,”

The researchers also proved how, showing that Akt1 causes the cancer cells to secrete a factor – CXCL16 – that promotes breast cancer cell migration. Without Akt, cancer cells failed to migrate. They also showed that deleting Akt1 completely blocked breast cancer metastasis to the lungs, while mice that expressed Akt1 died from lung metastasis.

While scientists have looked at Akt as a drug target, notes Arthur Pardee, Ph.D., professor emeritus of medical oncology at the Dana-Farber Cancer Institute in Boston, its role in metastasis is less emphasized. “Blocking this with anti-Akt drugs might provide a novel treatment, especially against early cancers,” he says.

While the monoclonal antibody drug Herceptin has been very successful in treating ErbB2-positive breast cancer, patients can relapse, Dr. Pestell notes, and other drug targets are needed. The newly found secreted factor may prove to be such a target.

Source: Thomas Jefferson University

Explore further: Chronic inflammation linked to 'high-grade' prostate cancer

add to favorites email to friend print save as pdf

Related Stories

Researchers map new path to colon cancer therapy

Dec 15, 2008

University of Texas Medical Branch at Galveston researchers have identified a promising new target in the battle against colorectal cancer — a biochemical pathway critical to the spread of tumors to new locations in the ...

Recommended for you

Cancer stem cells linked to drug resistance

6 hours ago

Most drugs used to treat lung, breast and pancreatic cancers also promote drug-resistance and ultimately spur tumor growth. Researchers at the University of California, San Diego School of Medicine have discovered ...

Unraveling the 'black ribbon' around lung cancer

Apr 17, 2014

It's not uncommon these days to find a colored ribbon representing a disease. A pink ribbon is well known to signify breast cancer. But what color ribbon does one think of with lung cancer?

User comments : 0

More news stories

Less-schooled whites lose longevity, study finds

Barbara Gentry slowly shifts her heavy frame out of a chair and uses a walker to move the dozen feet to a chair not far from the pool table at the Buford Senior Center. Her hair is white and a cough sometimes interrupts her ...

Low tolerance for pain? The reason may be in your genes

Researchers may have identified key genes linked to why some people have a higher tolerance for pain than others, according to a study released today that will be presented at the American Academy of Neurology's 66th Annual ...

How to keep your fitness goals on track

(HealthDay)—The New Year's resolutions many made to get fit have stalled by now. And one expert thinks that's because many people set their goals too high.

Growing app industry has developers racing to keep up

Smartphone application developers say they are challenged by the glut of apps as well as the need to update their software to keep up with evolving phone technology, making creative pricing strategies essential to finding ...

Making graphene in your kitchen

Graphene has been touted as a wonder material—the world's thinnest substance, but super-strong. Now scientists say it is so easy to make you could produce some in your kitchen.