Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

One Wwox isn't enough (to protect against cancer)

19.03.2007
A new study shows that the loss of even one of the two copies of a particular tumor-suppressor gene greatly increases the risk that lung cancer will develop in experimental animals.

The study examined the Wwox gene, a suspected tumor-suppressor gene, and showed that even when mice have one working copy of the gene, they nonetheless develop five times more lung tumors than do mice with both copies of the gene. Tumor-suppressor genes normally keep damaged cells from becoming cancerous.

The findings were published in the Proceedings of the National Academy of Sciences by investigators at the Ohio State University Comprehensive Cancer Center.

“Classic tumor-suppressor genes don't increase cancer risk until cells lose both copies of the gene or when both copies are mutated,” says first author Rami I. Aqeilan, research assistant professor of molecular virology, immunology and medical genetics at Ohio State.

... more about:
»Aqeilan »Wwox »develop »lung cancer

“These findings suggest that losing one copy of Wwox can predispose normal cells to become cancerous. This emphasizes the importance that Wwox may have in initiating the disease.”

Surprisingly, the research also links loss of the gene and a form of bone cancer called chondroid osteosarcoma. The research may offer the first animal model for the study of this human disease.

Osteosarcoma is rare in humans, but it is the most common form of bone tumor and the second highest cause of cancer-related death in children, after leukemia, he says.

“Osteosarcoma forms at an early age due to the rapid growth of the bones and skeleton,” says Aqeilan, who is also a researcher with the Ohio State human cancer genetics program.

“These mice have given us a very interesting clue that loss of both copies of Wwox gene may initiate tumors in the bone.”

This study initially set out to prove that Wwox is a bona fide tumor suppressor gene. The gene is missing or altered in 85 percent of lung cancers, 65 percent of breast cancers, and in a high proportion of cancers of the stomach, colon and prostate and some lymphomas.

Wwox is located on chromosome 16, spanning a region called a fragile site, a place where the chromosome often breaks during environmental stress. Breakage at fragile sites results in the loss of pieces of chromosomes and in chromosomal abnormalities. Both can lead to cancer.

“The location of this gene in a fragile site is important,” Aqeilan says. “Our findings suggest that if an environmental stress, such as tobacco smoke, causes the loss of one copy of the gene, it might predispose a person to lung cancer.”

For this study, Aqeilan and colleagues at Ohio State and the University of Massachusetts Medical School developed strains of mice that were missing one copy of the Wwox gene. The mice were bred to produce animals lacking both Wwox genes and mice having both copies of the gene. Mice with both copies served as controls.

Mice born with no copies of Wwox died by four weeks of age. Thirteen of those animals were studied closely, and four of them (31 percent) showed evidence of early osteosarcoma.

Of 58 animals with only one copy of the gene, 16 percent – or nearly one in six – developed lung cancer compared with only 3 percent of the control mice, a five-fold increase.

The researchers also exposed animals with one copy of the gene to a carcinogen, ethyl nitrosourea, to learn about the kinds of tumors that Wwox might help suppress.

Of 46 animals exposed to the chemical, 80 percent developed tumors vs. just under half of control animals that had both copies of the gene. Most of the animals developed lung cancer or lymphoma. Liver cancer, squamous cell carcinoma and malignant B-cell infiltration into the liver and lungs developed in small numbers.

The researchers are now looking for the loss of Wwox in human osteosarcomas and are generating a mouse model that will allow them to study the ability of the gene to reverse tumor growth after it is restored in adult animals with cancer.

“Wwox-mutant mice are useful in understanding the role of this gene in human cancer, and they provide models for studying the carcinogenecity of compounds, and the development, prevention and treatment of common cancers,” Aqeilan says.

A Kimmel Scholar Award and funding from the National Cancer Institute supported this research.

Other OSU researchers involved in this study were Francesco Trapasso, Stefan Costinean, Dean Marshall, Yuri Pekarsky, John P. Hagan, Nicola Zanesi, Mohamed Kaou and Carlo M. Croce.

Darrell E. Ward | EurekAlert!
Further information:
http://www.osumc.edu

Further reports about: Aqeilan Wwox develop lung cancer

More articles from Life Sciences:

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

nachricht Pollen taxi for bacteria
18.07.2018 | Technische Universität München

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

NYSCF researchers develop novel bioengineering technique for personalized bone grafts

18.07.2018 | Life Sciences

Machine-learning predicted a superhard and high-energy-density tungsten nitride

18.07.2018 | Materials Sciences

Why might reading make myopic?

18.07.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>