Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New protein identified in development of lung cancer

17.11.2004


A newly-identified protein that can flag an important tumor suppressor gene for destruction may be a key player in the development of lung cancer.



Writing in the Nov. 17 issue of the Journal of the National Cancer Institute, scientists in the Ohio State University Comprehensive Cancer Center (OSUCCC) note that the protein, called Pirh2, when overexpressed, diminishes the activity of p53 – possibly the most powerful tumor suppressor in the entire genome. When it functions normally, p53 regulates several critical cellular processes, including cell growth and death, DNA repair and angiogenesis, the formation of new blood vessels. Studies show that p53 mutation is common, occurring in at least half of all cancer.

“The p53 gene is possibly the most important ‘manager’ in a cell. When it’s not working properly, it can be disastrous,” says Miguel Villalona, associate professor of internal medicine in the Ohio State University College of Medicine and Public Health and senior author of the study. Villalona says that this is the first time Pirh2 has been implicated in the loss of p53 function in tumors.


Villalona and his colleagues identified the link between Pirh2 and the development of cancer by evaluating Pirh2 expression in human and mouse lung tumor samples and comparing it with Pirh2 expression in normal tissue from the same samples. They found that Pirh2 expression was higher in 27 of 32 (84 percent) of human lung cancers and in 14 of 15 (93 percent) of mouse tumors than it was in the normal tissue. “This is the first demonstration that Pirh2 expression is elevated in patients’ tumors and supports the notion that it may be an important molecule in the development of lung cancer, says Gregory Otterson, associate professor of internal medicine in the OSU College of Medicine and Public Health and co-author of the study.

Wenrui Duan, the lead author of the study and a research scientist in the department of internal medicine, says that when Pirh2 is overexpressed, it “acts like glue,” binding a substance called ubiquitin to p53 protein. Ubiquitin acts like a flag, telling the cell’s recycling center – the proteasome – that the proteins are ready to be destroyed. Destruction of the proteins essentially cripples p53 and opens the door to malignant transformation. Supporting that notion, the researchers discovered that p53 protein was more ubiquitinated in the mouse lung cancers than in the normal tissue, and that generally, p53 expression was lower in tumor tissue than in normal tissue.

Interestingly, additional analysis revealed that Pirh2 overexpression is not related to any mutations in p53 – only loss of function. “In effect, we’ve discovered that Prih2 is an oncogene. It promotes cancer by undermining the tumor suppressor’s ability to do its job,” says Duan. At the same time, these findings may offer scientists a possible new target for intervention.

Villalona points out that new drugs are already on the market that can inhibit the activity of the proteasome, and suggests that these drugs may be able to counter Pirh2’s oncogenic behavior by restoring p53 function. Additional studies would be needed to demonstrate that, however. “We clearly need of new ways to fight lung cancer,” says Villalona, noting that lung cancer is the leading cause of cancer death in the United States and claims more than one million lives worldwide every year.

Grants from the National Cancer Institute supported the study.

Additional investigators from Ohio State who contributed to the project include Li Gao, Lawrence Druhan, Wei-Guo Zhu and Carl Morrison.

Michelle Gailiun | EurekAlert!
Further information:
http://www.osu.edu

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>