Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

If you think cancer genes are simple, you don't know JAK

19.09.2007
Cancer-causing genes can work in more powerful and sneaky ways than have been realized. Scientists have shown that a gene named JAK that is closely related to a common cancer-causing gene in people tips the scales toward cancer in an unexpected manner. JAK disrupts the activity of an organism’s DNA on a broad scale, thwarting a critical molecular event very early on in an embryo’s development.

A team from the University of Rochester Medical Center made the finding, published in the Sept. 7 issue of Public Library of Science (PLoS) Genetics, through research involving fruit flies, which share much of the same complex cellular signaling as humans. Sorting out the major molecular processes in fruit flies or other comparatively simple organisms first has often allowed scientists studying diseases like cancer to speed the development of new treatments by years or even decades.

By manipulating the DNA of fruit flies and analyzing their body types as they develop – as maggots – the team made a surprising finding: The cancer-promoting effects of a mutation to the DNA sequence of a gene that normally suppresses cancer can be passed from parents to offspring, even if the mutation itself is not passed to the offspring. Under some circumstances, having one parent with the mutation is enough to ultimately affect the offspring, even when the mutation itself is not passed to the next generation.

The work offers a stark illustration of a reality that scientists are coming to fully respect only recently: Even though the DNA code has been traditionally considered the only way to pass genetic information through the generations, there are other, more subtle genetic legacies, types of a “molecular memory” that can go from generation to generation as well.

The team made the finding with a cancer-causing gene, or oncogene, known as an activated JAK kinase. A biochemical system extremely similar to JAK is vital for people’s health, but when its signals run amok, the system can play a role in the development of leukemia or lymphoma.

For decades, scientists have been teasing out DNA’s secrets, learning how one snippet of DNA controls another, how some genes wield incredible power over others, and how the DNA code encrypts all kinds of biochemical signals – start, stop, turn on, turn off, and so on. Scientists have made great progress understanding the complex signals that govern diseases like cancer, often finding that a key gene that should be on is turned off, or that a gene that is supposed to be off is turned on, or that a mutant gene creates a faulty protein that doesn’t work correctly.

Now researchers are trying to make more sense of the glut of genetic information becoming available. For instance, what does a given sequence of chemical bases that make up our DNA, such as ACTGGGCTAGTTGGCAGT, really mean for our health" Scientists are turning more attention to the big picture, looking at broad mechanisms that determine how our bodies interpret the DNA, the master blueprint that controls how an organism develops and functions. It’s part of a body of work known as “epigenetics.” The main idea is that genetic information can be regulated on a more global scale than just on a gene-by-gene basis, which has been the focus of much genetic research thus far.

The team, based in the University’s Department of Biomedical Genetics and the James P. Wilmot Cancer Center, has shown how epigenetic information can play a significant role in causing cancer.

“You might assume that a fruit fly that inherits a mutation that can increase cancer is more at risk for the disease than its sibling that does not inherit that mutation,” said geneticist Willis Li, Ph.D., the lead author of the study and associate professor in the Department of Biomedical Genetics.

“We have found an example where this is not true. We found that the cancer-causing effects of certain mutations can persist in cells that don’t even carry the damaged gene, and that these effects can be passed from one generation to the next even though they’re not actually in the DNA code. The mutation’s effects on the DNA of one of its parents affect the genes of its offspring. Even though the mutation is in one fly but not in another, both are affected equally,” said Li.

To understand the work, it helps to think of large stretches of DNA, sometimes encompassing many genes, as valuable parcels of information that must be handled with precision and great care, not only as they are passed from generation to generation but also during the lifespan of an individual. Such packages contain little flags or markings. Just as a regular package might have the words “handle with care” stamped on it, our DNA has chemical signals that tell the body things like, “Don’t turn this set of genes on” or “Turn these genes on only in case of emergency.” No matter what’s “inside the package” – no matter the specific DNA code – such chemical signals on the outside provide instructions that help the body determine what to do with the DNA.

The instructions frequently come through a mechanism known as DNA methylation, which the body uses often to turn genes off. Normally, such chemical markings are wiped clean and reset very early in an organism’s life through a process known as epigenetic reprogramming. But Li’s team showed that JAK – specifically an activated JAK kinase known as HOP-Tum-l – can disrupt that reprogramming, so that the offspring inherit the methylation pattern of a parent. In other words, the specific pattern of genes that are destined to be turned on or off – the instructions for what to do with the DNA – is mistakenly passed on from parent to offspring.

While scientists have known that epigenetic information can be passed from generation to generation, Li says this is the first time the phenomenon has been linked to a cancer-causing gene.

To do the study, Li’s team focused on the interaction between JAK and a gene known as Krüppel, best known for playing a major role in the development of a fruit fly’s body. It turns out that Krüppel also enhances an organism’s ability to suppress tumors, and if the normal gene is knocked out or replaced by a faulty version, an organism is more likely to develop cancer when another cancer-causing gene like JAK is present.

His team found that some flies with a normal version of Krüppel got just as many tumors as their brethren with the bad copy – about three times as many tumors as most fruit flies with the normal version – simply because one of their parents harbored the JAK oncogene. Scientists believe the JAK mutation somehow messed up the “package” that contained Krüppel, and this damage causes problems a generation later, even when the faulty Krüppel gene is no longer around.

“In Jurassic Park, all the knowledge that was needed to re-create dinosaurs was gotten out of ancient DNA embedded in amber,” said Dirk Bohmann, Ph.D., a colleague and fellow fruit-fly researcher who was not directly involved in the study. “Willis and other scientists are showing that there is so much more that goes into controlling and regulating genetic information than just knowledge of the DNA code. Michael Crichton would have a harder time making that film today, given what has been discovered in recent years.

“This work tells us that we have to pay more attention to the ways in which DNA is packaged. It’s not just about the DNA sequence,” Bohmann added.

Last year in a paper in Nature Genetics, Li first showed that JAK is a more powerful oncogene than previously thought, with the ability to turn on cancer-causing genes that are normally silent, through another epigenetic mechanism involving gene packaging. The new work shows that the gene is also able to suppress cancer-suppressing genes that are normally turned on, making JAK even more of a threat than had been known.

Work like Li’s is getting the attention of pharmaceutical companies, which are developing drugs that target an organism’s DNA governance at the epigenetic or “packaging” level. Such work provides a new target for developing drugs to stop cancer, and it reminds scientists just how much more research is necessary before we fully understand the workings of ACTGGGCTAGTTGGCAGT and the countless other DNA sequences in our body.

Tom Rickey | EurekAlert!
Further information:
http://www.urmc.rochester.edu

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Nagoya physicists resolve long-standing mystery of structure-less transition

21.08.2017 | Materials Sciences

Chronic stress induces fatal organ dysfunctions via a new neural circuit

21.08.2017 | Health and Medicine

Scientists from the MSU studied new liquid-crystalline photochrom

21.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>