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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New gene catalog of ocean microbiome reveals surprises

18.08.2017 | Life Sciences

Astrophysicists explain the mysterious behavior of cosmic rays

18.08.2017 | Physics and Astronomy

AI implications: Engineer's model lays groundwork for machine-learning device

18.08.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>