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 Cells communicate in a dynamic code
19.02.2018 | California Institute of Technology

nachricht Studying mitosis' structure to understand the inside of cancer cells
19.02.2018 | Biophysical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Contacting the molecular world through graphene nanoribbons

19.02.2018 | Materials Sciences

When Proteins Shake Hands

19.02.2018 | Materials Sciences

Cells communicate in a dynamic code

19.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>