Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists find unusual lung-cancer tumor-suppressor gene

19.01.2006


Researchers have identified a new and unusual tumor suppressor gene that may be important in cancers of the lung and head and neck. The study shows that restoring the inactivated gene can slow the growth of tumor cells.



The gene, known as TCF21, is silenced in tumor cells through a chemical change known as DNA methylation, a process that is potentially reversible.

The findings might therefore lead to new strategies for the treatment and early detection of lung cancer, a disease that killed an estimated 163,510 Americans in 2005. The study could also lead to a better understanding of the molecular changes that occur in tumor cells during lung-cancer progression.


Tumor-suppressor genes are genes that normally prevent cells from growing out of control. The loss or silencing of one or more tumor-suppressor genes is believed to be an important part of cancer development.

The study, by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, was published online in the Jan. 13 early edition of the Proceedings of the National Academy of Sciences.

The newly discovered gene is unusual because it can alter normal epithelial cells, causing them to change to a more primitive state. Epithelial cells form the skin and line the body’s passageways and hollow organs. They are also the source of the most common forms of cancer.

The more primitive cell type, known as a mesenchymal cell, is more commonly found in embryos and is capable of migrating to other tissues. This suggests that the silencing of the TCF21 gene might help a tumor to spread to other areas of the body, a process known as metastasis.

The gene is also often silenced or lost in a variety of other cancers, including breast and ovarian cancer, melanoma and lymphoma.

“The fact that this gene is silenced in many cancer types strongly suggests that it plays an important role in cancer development,” says principal investigator Christoph Plass, a professor of molecular virology, immunology and medical genetics and a researcher in the OSU Human Cancer Genetics Program.

In addition, says first author Laura T. Smith, a postdoctoral fellow in Plass’ laboratory, “because this gene is silenced by DNA methylation, it might be possible to reactivate it using drugs that reverse the methylation process. This could provide a new strategy for treating these cancers.”

The gene is found on chromosome 6 in a region known as 6q23-24, an area that contains hundreds of genes. Other researchers have searched this region looking for mutations that might lead them to a silenced tumor-suppressor gene, but, Plass says, “that strategy has been unsuccessful.”

DNA methylation, which is a chemical change and not a mutation, is another way that genes are silenced. For this study, Plass and his colleagues systematically scanned the same chromosome region using a technology known as restriction landmark genome scanning, which identifies methylated genes.

The researchers examined the region in about 50 tumor samples from patients with head and neck squamous-cell carcinomas and with non-small-cell lung cancer, which is responsible for about 85 percent of lung cancer cases. From this, they identified TCF21 as a gene often silenced by methylation compared with normal airway cells.

“A picture is emerging that certain genes tend to be silenced mainly by DNA methylation, while others tend to be silenced by genetic mutations,” Plass says. “This gene seems to be silenced by DNA methylation.”

Through a series of experiments, Plass and his colleagues showed that an active TCF21 gene can, in fact, be silenced by DNA methylation, and that drugs that reverse methylation can reactive it.

The researchers also used a lung-cancer cell line to show that if the active version of the TCF21 gene is placed in tumor cells, the active gene will slow the cells’ growth rate.

Lastly, the researchers showed that mice injected with lung-tumor cells that had an active TCF21 gene developed tumors that were two to three times smaller than tumors that developed from cancer cells with a silent TCF21 gene.

Plass and his colleagues are now studying the possible role of TCF21 in metastasis.

Funding from the National Cancer Institute and the National Institute of Dental and Craniofacial Research supported this research.

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

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>