Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene identified that prevents stem cells from turning cancerous

15.10.2010
Stem cells, the prodigious precursors of all the tissues in our body, can make almost anything, given the right circumstances. Including, unfortunately, cancer.

Now research from Rockefeller University shows that having too many stem cells, or stem cells that live for too long, can increase the odds of developing cancer.

By identifying a mechanism that regulates programmed cell death in precursor cells for blood, or hematopoietic stem cells, the work is the first to connect the death of such cells to a later susceptibility to tumors in mice. It also provides evidence of the potentially carcinogenic downside to stem cell treatments, and suggests that nature has sought to balance stem cells' regenerative power against their potentially lethal potency.

Research associate Maria Garcia-Fernandez, Hermann Steller, head of the Strang Laboratory of Apoptosis and Cancer Biology, and their colleagues explored the activity of a gene called Sept4, which encodes a protein, ARTS, that increases programmed cell death, or apoptosis, by antagonizing other proteins that prevent cell death. ARTS was originally discovered by Sarit Larisch, a visiting professor at Rockefeller, and is found to be lacking in human leukemia and other cancers, suggesting it suppresses tumors. To study the role of ARTS, the experimenters bred a line of mice genetically engineered to lack the Sept4 gene.

For several years, Garcia-Fernandez studied cells that lacked ARTS, looking for signs of trouble relating to cell death. In mature B and T cells, she could not find any, however, so she began to look at cells earlier and earlier in development, until finally she was comparing hematopoietic progenitor and stem cells. Here she found crucial differences, to be published Friday in Genes and Development.

Newborn ARTS-deprived mice had about twice as many hematopoietic stem cells as their normal, ARTS-endowed peers, and those stem cells were extraordinary in their ability to survive experimentally induced mutations.

"The increase in the number of hematopoietic progenitor and stem cells in Sept4-deficient mice brings with it the possibility of accelerating the accumulation of mutations in stem cells," says Garcia-Fernandez. "They have more stem cells with enhanced resistance to apoptosis. In the end, that leads to more cells accumulating mutations that cannot be eliminated."

Indeed, the ARTS-deprived mice developed spontaneous tumors at about twice the rate of their controls. "We make a connection between apoptosis, stem cells and cancer that has not been made in this way before: this pathway is critically important in stem cell death and in reducing tumor risk," Steller says. "The work supports the idea that the stem cell is the seed of the tumor and that the transition from a normal stem cell to a cancer stem cell involves increased resistance to apoptosis."

ARTS interferes with molecules called inhibitor of apoptosis proteins (IAPs), which prevent cells from killing themselves. By inhibiting these inhibitors, under the right circumstances ARTS helps to take the brakes off the process of apoptosis, permitting the cell to die on schedule. Pharmaceutical companies are working to develop small molecule IAP antagonists, but this research is the first to show that inactivating a natural IAP antagonist actually causes tumors to grow, Steller says. It also suggests that the premature silencing of the Sept4/ARTS pathway at the stem cell level may herald cancer to come.

"This work not only defines the role of the ARTS gene in the underlying mechanism of mammalian tumor cell resistance to programmed cell death, but also links this gene to another hallmark of cancer, stem and progenitor cell proliferation," said Marion Zatz, who oversees cell death grants, including Steller's, at the NIH's National Institute of General Medical Sciences. "The identification of the ARTS gene and its role in cancer cell death provides a potential target for new therapeutic approaches."

Brett Norman | EurekAlert!
Further information:
http://www.rockefeller.edu

More articles from Life Sciences:

nachricht Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen

nachricht New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Unraveling the nature of 'whistlers' from space in the lab

15.08.2018 | Physics and Astronomy

Diving robots find Antarctic winter seas exhale surprising amounts of carbon dioxide

15.08.2018 | Earth Sciences

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>