Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Team finds link between stomach-cancer bug and cancer-promoting factor

07.01.2010
Researchers report that Helicobacter pylori, the only bacterium known to survive in the harsh environment of the human stomach, directly activates an enzyme in host cells that has been associated with several types of cancer, including gastric cancer.

Chronic infection with H. pylori is a well-documented risk factor for several forms of gastric cancer, but researchers have not yet determined the mechanisms by which specific bacterial factors contribute to cancer development. Nearly one-half of the world’s population is infected with H. pylori, and gastric cancer is one of the leading causes of cancer-related death.

The new study, in Proceedings of the National Academy of Sciences, is the first to show that a factor produced by the bacterium directly activates poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme found primarily within the nucleus of animal cells. PARP-1 is a regulator of the host’s inflammatory response and host cell death, both of which are hallmarks of H. pylori infection.

PARP-1 is best known as a normal part of the cellular machinery that repairs damaged DNA. But in certain types of cancer this enzyme actually enhances tumor survival and undermines chemotherapies designed to damage DNA in cancer cells. A recent human clinical trial found that drugs that inhibited PARP-1 reduced tumor growth in breast-cancer patients with mutations in certain DNA-repair (BRCA-1 and BRCA-2) genes. BRCA-1 mutations also are associated with an increased risk of stomach cancer.

The new study tackled the most urgent health problem associated with H. pylori infection, said Steven Blanke, a University of Illinois professor in the department of microbiology and Institute for Genomic Biology and principal investigator on the study.

“What is it about sustained infection with H. pylori that leads in some cases to the development of stomach cancer?” he said.

Like other disease-causing bacteria, H. pylori have evolved to evade the body’s defenses and even modify host proteins to help the bacteria survive.

Blanke and his graduate student Carlos Nossa previously had demonstrated that a protein factor released by H. pylori modifies an unidentified host protein in a manner consistent with an enzymatic reaction known as ADP-ribosylation. Other bacterial toxins, including cholera toxin and diphtheria toxin “ADP-ribosylate” host proteins in ways that enhance the survival or transmission of the bacteria that produce them.

“We were very excited about this finding, which we published in 2006,” Blanke said. “We thought we had discovered a new toxin.”

ADP-ribosylation can be tracked by incorporating a radio-isotope of phosphorous (32P) into a small molecule that is required for the reaction. During ADP-ribosylation, H. pylori transfers the 32P from the labeled molecule to a host protein, thereby tagging it with a radioactive fingerprint. Further analyses revealed that the radio-labeled host protein was PARP-1.

At this point, the team believed that the bacterium was ADP-ribosylating PARP-1. But when they genetically altered the functional regions of PARP-1, they completely blocked the H. pylori-dependent modification. Since PARP-1 also possesses poly-ADP-ribosylation enzymatic activity, which is necessary for its regulatory and DNA-repair function in cells, the team realized that something in the H. pylori arsenal was directly activating the PARP-1 enzymatic activity, rather than ADP-ribosylating it as they first suspected.

Additional studies validated that H. pylori indeed activates PARP-1 during infection of human gastric cells.

“These studies potentially provide a direct molecular link between H. pylori infection and the activation of a factor known to be involved in the survival of cancerous cells,” Blanke said. “Although PARP-1 can potentially be activated indirectly as a host cell response to some infections, this is the first example of a bacterium that can activate PARP-1 directly, perhaps in this case as a mechanism for H. pylori to promote inflammation and/or the death of host cells during long-term infection.”

The researchers are working to identify the bacterial factor that activates PARP-1, which would be a promising target for drugs to treat or prevent the problems associated with long-term infection with H. pylori, Blanke said.

The team also included researchers from the University of Houston; Ecole Supérieure de Biotechnologie Strasbourg, Illkirch, France; and Laval University, Quebec.

This study was supported from a grant from the National Institutes of Health.

Diana Yates | EurekAlert!
Further information:
http://www.illinois.edu

More articles from Health and Medicine:

nachricht World first: Massive thrombosis removed during early pregnancy
20.07.2017 | Universitätsspital Bern

nachricht Therapy of preterm birth in sight?
19.07.2017 | Universitätsspital Bern

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>