Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sleeping beauty plays a significant role in identifying cancer genes

14.07.2005


Researchers at the University of Minnesota Cancer Center and the National Cancer Institute (NCI), part of the National Institutes of Health, have discovered a new method that could accelerate the way cancer-causing genes are found and could lead to a more accurate identification of the genes, according to two studies in the July 14, 2005, issue of Nature*.

The gene identification method was developed in genetically modified mice and utilized a piece of jumping DNA, called Sleeping Beauty. Jumping genes, or transposons, insert themselves into or between genes and can activate or inactivate a gene’s normal function. Related transposons are natural to the genetic makeup of humans, animals and fish, but, through millions of years of evolution, most transposons became inactive dead-ends. In 1997, in another study, University of Minnesota researchers took defunct, non-functioning jumping genes from fish and made the genes jump again. This research had reactivated the jumping genes from millions of years of evolutionary sleep; hence the name Sleeping Beauty.

In the two current research studies, specially designed Sleeping Beauty transposons were introduced into mouse DNA and made to jump around in the nucleus of mouse cells. Eventually the transposons jumped into cancer-causing genes and caused a tumor to form. By isolating and studying the genes from tumors that contained Sleeping Beauty, researchers were able to efficiently find genes linked to cancer by seeing whether Sleeping Beauty turned them on or off -- in effect, uncovering the fingerprint of each tumor’s cancer genes.



David Largaespada, Ph.D., associate professor and leader of the Genetic Mechanisms of Cancer Program, led the University of Minnesota Cancer Center research team. Their work focused on cancer gene discovery in solid tumors using transposon-based techniques. "Current cancer gene identification methods, such as microarrays, give correlations typically of thousands of genes, and it’s hard to know from the correlations which genes relate to cancer and which do not," said Largaespada. "By comparison, the jumping gene has inserted itself into cancer genes in the tumors we studied and thereby allows us to focus on smaller numbers of genes -- genes that we know are important to the genesis of tumors. The result is a quicker, more efficient and accurate identification of cancer-causing genes."

Nancy Jenkins, Ph.D., head of NCI’s Molecular Genetics of Development, and Neal Copeland, Ph.D., head of the Molecular Genetics of Oncogenesis in the Mouse Cancer Genetics program, led the NCI research team, which investigated the use of a highly mobile Sleeping Beauty transposon system to study lymphomas, a cancer that strikes the immune system.

"Although our discovery was made in laboratory mice," said Jenkins, "we believe that the technology used will reveal new insights into human cancer and could be translated for clinical use. Hopefully, this discovery will speed up the development of new drugs and improve already-in-use drugs that target specific genes for treatment of various types of cancer, including lymphomas.

The outcome of the new Sleeping Beauty method could be a major leap forward in understanding cancer’s weak points and thus lead to better treatments."

According to Largaespada, "About 300 human cancer-related genes have thus far been reported in the scientific literature. Most of those identified are involved in cancers of the blood system. So, there are likely to be many more cancer genes that still need to be identified."

Additionally, he noted that the Sleeping Beauty technology is capable of providing important information about the genes that current methods do not -- such as the specific combinations of mutant genes that can work together to cause cancer. "With this information, we will understand the development of tumors at the genetic level in much finer detail," he said. "This is important because no single kind of cancer is going to be cured by one drug; it is going to take a combination of drugs to attack the pathways that are required for cancer to start and continue growing."

The next step for Largaespada, Jenkins, Copeland and their colleagues will be to generate and analyze a large number of other tumors induced in mice using the Sleeping Beauty jumping gene. Largaespada and his team will focus on identifying genes causing prostate, lung and colorectal cancer; Jenkins and her team will study genes for tumors in the brain, melanoma, breast, leukemia and lymphoma.

Largaespada, Jenkins and Copeland acknowledge the difference between research in mice and actual use in humans. But as Largaespada pointed out, "We have proof of principle that we’re on the right track. We know that some of the same genes that are mutated in cancer in mice using Sleeping Beauty are also mutated in the same form of cancer in humans. An example is the Notch1 gene, which was mutated in 50 percent of mice with T cell lymphoma induced by Sleeping Beauty. The same gene is mutated in about 50 percent of people with a similar type of cancer. We believe the Sleeping Beauty method will allow us to identify many other such genes for other cancers."

*Collier L., Carlson C., Ravimohan S., Dupuy A., Largaespada D. "Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse," Nature, Vol. 436, No. 7047.

Dupuy A., Akagi K., Largaespada D., Copeland N., Jenkins N. "Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system," Nature, Vol. 436, No. 7047.

Michael Miller | EurekAlert!
Further information:
http://www.nih.gov

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>