Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stanford study reveals protein’s Jekyll-and-Hyde role in cancer growth

21.10.2005


Tumor-suppressor proteins work to inhibit tumor growth in our bodies and when they win, they spare us a battle with cancer. But one such protein, menin, appears to have a split personality. Though menin is well-known for its ability to suppress endocrine tumors, researchers at Stanford University School of Medicine have discovered that it is also a key player in the development of some forms of acute leukemia.



The researchers, who made the discovery in working with mouse cells, say this is the first time a tumor-suppressor protein has been found to have such a dramatic dual role. But there may be a silver lining in menin’s dark side - understanding the mechanism could open up new avenues of treatment for the very leukemias that menin promotes.

Normally menin binds with another protein, known as MLL, in the nucleus of a cell, where the two are part of a complex of proteins that promote proper cell growth. But when MLL is mutated, it becomes a cancer-promoting oncoprotein. Usually this would put the tumor suppressor and the oncoprotein in direct conflict, as each sought to overwhelm the other, but not so in cases of acute leukemia. "We’ve discovered a situation where they’re not antagonizing each other’s actions, they’re actually working together," said Michael Cleary, MD, professor of pathology and of pediatrics and senior author of the paper published in the Oct. 21 issue of Cell.


When the blood system is functioning properly, the menin and the normal MLL proteins work together constructively, helping guide cells through all the stages of development from their beginnings as blood-forming stem cells to final maturation, or differentiation, into blood cells. But when MLL is mutated, the differentiation process stalls at an intermediate stage and the immature cells begin proliferating uncontrollably.

Given that menin is highly effective in suppressing endocrine tumors, Cleary and first author Akihiko Yokoyama, a postdoctoral scholar in pathology, suspected that MLL was somehow deactivating menin’s suppressive powers. They tested the theory with mouse cells in vitro by introducing the mutated MLL oncoprotein and letting leukemia begin to thrive. Yokoyama then genetically removed menin from the cancer cells.

If menin and MLL were struggling against each other, the researchers reasoned that removing menin would either have no effect on the rate of proliferation, or the leukemia would run even wilder, flourishing without restraint. But the leukemia ground to a halt.

"The cells actually stopped proliferating," said Yokoyama, adding, "If you had to predict the outcome, you would’ve predicted exactly the opposite of what occurred."

Even more unexpected was what happened next - the former cancer cells matured. Like juvenile delinquents steered away from a life of crime when a bad influence is removed, the immature blood cells not only ceased their bad behavior once the menin was gone, they resumed productive lives. They completed the differentiation process and became mature blood cells. The leukemia disappeared without a single cancer cell being killed.

Further work by Yokoyama established that menin was actively involved in promoting the acute leukemia, rather than simply being passive raw material for MLL to use. "This is the first example that we know of where an oncoprotein and a tumor-suppressor protein are physically working together to promote cancer," said Cleary.

Exactly what causes menin to behave as it does in acute leukemia isn’t clear. What at first appears to be Jekyll-and-Hyde behavior may simply be a matter of slavish devotion to its mission, with the protein plying the only trade it knows regardless of whether its actions inhibit cancer or, in the case of acute leukemia, promote it.

Not knowing just how menin does what it does, the researchers said it’s difficult to speculate whether similar processes could be happening elsewhere in the human body. But the findings offer tantalizing possibilities for pursuing new treatments for MLL-associated acute leukemias, which make up between 5 and 10 percent of all leukemias in both adults and children. Acute leukemias associated with MLL oncoproteins are extremely aggressive and patients generally don’t respond well to conventional treatments.

But the stunning reversal of leukemia in the mouse cells when menin was removed offers clues for developing treatments. If the team’s findings can be applied to humans, "we would probably stop a leukemia dead in its tracks," said Cleary. There’s a lot more that needs to be learned before that could be attempted, but Yokomama and Cleary are cautiously optimistic.

"We’re chipping away at the molecular mechanism for how the MLL oncoprotein works," said Cleary. "The more basic knowledge we have, the more chance we have of designing more effective and specific treatments."

Other Stanford researchers involved in the study are Tim Somervaille, MD, PhD, postdoctoral scholar in pathology, and Kevin Smith, PhD, basic life science research associate in pathology.

Louis Bergeron | EurekAlert!
Further information:
http://www.stanford.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>