Featured Research

from universities, journals, and other organizations

Stomach-cancer bug linked to cancer-promoting factor

Date:
January 7, 2010
Source:
University of Illinois at Urbana-Champaign
Summary:
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.

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 phosphorus (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 Supιrieure de Biotechnologie Strasbourg, Illkirch, France; and Laval University, Quebec.

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


Story Source:

The above story is based on materials provided by University of Illinois at Urbana-Champaign. Note: Materials may be edited for content and length.


Journal Reference:

  1. Nossa et al. Activation of the abundant nuclear factor poly(ADP-ribose) polymerase-1 by Helicobacter pylori. Proceedings of the National Academy of Sciences, 2009; DOI: 10.1073/pnas.0906753106

Cite This Page:

University of Illinois at Urbana-Champaign. "Stomach-cancer bug linked to cancer-promoting factor." ScienceDaily. ScienceDaily, 7 January 2010. <www.sciencedaily.com/releases/2010/01/100106193330.htm>.
University of Illinois at Urbana-Champaign. (2010, January 7). Stomach-cancer bug linked to cancer-promoting factor. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2010/01/100106193330.htm
University of Illinois at Urbana-Champaign. "Stomach-cancer bug linked to cancer-promoting factor." ScienceDaily. www.sciencedaily.com/releases/2010/01/100106193330.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) — A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
Too Few Teens Receiving HPV Vaccination, CDC Says

Too Few Teens Receiving HPV Vaccination, CDC Says

Newsy (July 24, 2014) — The Centers for Disease Control and Prevention is blaming doctors for the low number of children being vaccinated for HPV. Video provided by Newsy
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) — The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) — Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins