Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancers’ love-hate relationship with proteins offers new treatment window

18.12.2003


Scientists at Washington University School of Medicine in St. Louis have found that the absence of two proteins cells use to cope with heat stress can make it easier for the cells to become cancerous, but that same absence also makes it harder for cancerous cells to survive exposure to heat and radiation.



The findings mark the two proteins, Heat shock protein (Hsp) 70.1 and 70.3, as potential targets for gene therapy that could increase cancer cells’ vulnerability to treatments.

"This is the first time we’ve linked these proteins to the cancer cell’s response to ionizing radiation," says Tej Pandita, Ph.D., assistant professor of radiation oncology and lead investigator of the new study. "Understanding the pathobiology of the genes that make these proteins -- how they function in normal circumstances and how they work in an unusual context like the cancer cell -- will help radiation oncologists devise gene therapy protocols that enhance cell kill from radiation treatments."


The findings will appear in the second January 2004 issue of Molecular and Cellular Biology (volume 24, issue 2), which will be available online on Dec. 28.

All cancers are caused to some degree by loss of genetic stability, according to Pandita. Genetic instability provides a chance for regulation of cell growth, cell division or other important processes to slip out of control, allowing a cancer to get its start. But too much genetic instability, a potential risk during the rapid and repeated cell division that is a hallmark of cancer, can increase vulnerability to stress and the chance that cells will self-destruct.

Pandita studies telomerase, an enzyme that helps maintain the telomeres, structures at the ends of chromosomes. Healthy cells normally only make telomerase when they’re preparing to divide and need the enzyme to stabilize the telomeres in preparation for replication of the genetic material. In cancerous cells, though, telomerase is present all the time.

Pandita began studying the Hsp 70.1 and 70.3 proteins because other scientists had revealed that they could act as chaperones for telomerase.

"Chaperone proteins interact with other proteins, helping to fold or unfold them, which helps activate their function; in other cases, they help deactivate and degrade the proteins they interact with," he explains. "To see what effect the heat shock proteins have on telomerase, we created a line of mice, in which the genes for the proteins were knocked out."

Cells lacking the proteins were close to becoming cancerous. Ends of chromosomes in the modified cells were more likely to become associated with each other, indicating the chromosomes’ telomeres probably were degraded. Telomerase normally contributes to the repair of this degradation and the mending of other genetic instability.

To get a more detailed sense of how vulnerable the cells had become, Pandita’s team exposed them to radiation and to heat followed by radiation. In test tube studies and in the genetically engineered mice, the heat followed by radiation killed more cancer cells.

If methods can be developed for blocking the creation of the Hsp proteins or for blocking their effects on telomerase, Pandita says, this result suggests that heat treatment followed by radiation treatment might produce the greatest benefits for cancer patients.


Hunt CR, Dix DJ, Sharma GG, Pandita RK, Gupta A, Funk M, Pandita RJ. Genomic instability and enhanced radiosensitivity in Hsp 70.1/3-deficient mice. Molecular and Cellular Biology, January 2004 (volume 24, issue 2).

Funding from the National Institutes of Health, the Department of the Army, Washington University School of Medicine Division of Radiation Oncology and the Environmental Protection Agency supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Michael C. Purdy | WUSTL School of Medicine
Further information:
http://aladdin.wustl.edu/medadmin/PAnews.nsf/news/C5E08D5A18C4516586256DFF006D59D3?OpenDocument
http://medinfo.wustl.edu/

More articles from Health and Medicine:

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

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: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

A new technique isolates neuronal activity during memory consolidation

22.06.2017 | Life Sciences

Plant inspiration could lead to flexible electronics

22.06.2017 | Materials Sciences

A rhodium-based catalyst for making organosilicon using less precious metal

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>