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 Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

nachricht 127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>