Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New protein associated with aggressiveness in breast and ovarian cancer

25.10.2004


A research team led by The University of Texas M. D. Anderson Cancer Center has found a potential new protein marker for prognosis of breast and ovarian cancer.



In the November, 2004 issue of the journal Nature Medicine, the researchers report tumor cells that "overexpress" the protein Rab25 are more aggressive and associated with poorer outcome. Thus, Rab25 could represent a novel therapeutic target or marker of tumor behavior, they say.

The researchers matched tumor samples to outcomes in about 100 patients diagnosed with either breast or ovarian cancer and found that a low level of Rab25 protein on a patient’s cancer sample was associated with a better clinical outcome in both cancer types. For example, patients with early stage (I and II) ovarian cancer who had low Rab25 tumor expression had an 80 percent survival five years after treatment, compared to 50 percent survival if Rab25 expression was high. In women with advanced breast cancer, a low level of Rab25 protein expression was associated with a 60 percent five-year survival, compared to 40 percent if Rab25 protein expression was high.


Adding this protein to other known molecular markers of progression could contribute to a "highly predictive test of outcome in breast or ovarian cancer," says the study’s lead investigator, Gordon Mills, M.D., Ph.D., a professor and chair of the Department of Molecular Therapeutics at M. D. Anderson. He adds that the protein might also, one day, be a target for cancer treatment. "We are pursuing Rab25 both as a test for outcomes and as a possible treatment."

Researchers from Lawrence Berkeley National Laboratory, the University of British Columbia, the University of California San Francisco, and Northwestern University participated in the research study, which was funded by the National Cancer Institute and the U. S. Department of Defense. The study is the first to link Rab25 to cancer, although several other members of the large Rab family of proteins, and the even bigger Ras protein superfamily to which it belongs, have been linked to the disease, says Mills. Members of the Ras protein family are mutated in a significant percentage of cancers, he says, and experimental drugs based on blocking Ras function are now being tested.

Rab proteins are anchored to intracellular membranes, and are activated when a receptor on the outside of the membrane is stimulated and the signal is brought into the cell. The "best current evidence" is that Rab25 is involved in deciding whether those internalized cell surface receptors "will either be degraded or will be returned to the cell surface," he says. Based on that knowledge, Mills and the team of researchers theorize that the receptors that Rab25 is deciding the fate of are those related to cell growth. "If you had more growth receptor going back to the surface instead of being degraded, you would have increased signaling, and more cell proliferation," says Mills. "But that working hypothesis has not yet been proven."

The other vital role of Rab25 is to activate the critical "PI3 kinase/AKT/PTEN" protein pathway involved in cell survival and growth. This pathway, however, is known to contain multiple tumor suppressor genes and oncogenes "and is targeted by genetic mutations in cancer more frequently than any other signaling pathway," says Mills. The fact that Rab25 is involved in this pathway "appears to be very important," and may provide a way to target the effects of Rab25, he adds.

The researchers discovered that the gene that produces the Rab25 protein is copied many more times than is normal in some breast and ovarian tumor cells, which then increases expression, or production, of the Rab25 protein. They then conducted laboratory in vitro cell line studies, and in vivo studies using human breast and ovarian tumor xerographs in mice, and were able to demonstrate that either increasing or decreasing expression of Rab25 altered tumor growth. Finally, using the human tumor samples, the researchers correlated Rab25 expression with survival. "We know now that change in expression is associated with a poorer patient outcome in both breast and ovarian cancer, and that may help us predict outcomes in patients in the future" says Mills. "But we have a long way to go to understanding exactly what it is that Rab25 is doing, and how we might be able to use it in treatment."

Co-authors include, from M. D. Anderson: Kwai Wa Cheng, Ph.D., John P. Lahad, Jinsong Liu, M.D., and Karen Lu, M.D.; from Lawrence Berkeley National Laboratory, Berkeley, CA: Wen-lin Kuo, Ph.D., Anna Lapuk, Ph.D., Kyosuke Yamada, Ph.D., and Joel Gray, Ph.D.; Nelly Auersperg, Ph.D., and David Fishman, M.D., from the University of British Columbia and Northwestern University respectively; Karen Smith-McCune, M.D., from the University of California San Francisco.

Nancy Jensen | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>