Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists establish database of genes associated with cancer drug resistance

24.08.2004


Scientists at the National Cancer Institute (NCI), a part of the National Institutes of Health, have created a database of information about a group of genes associated with multidrug resistance in cancerous tumors. The research, published in the August 24, 2004, issue of Cancer Cell*, details the gene expression of a 48-member family of proteins called ABC transporters. The NCI scientists identified associations between expression of individual ABC transporters in cancer cells and resistance to specific drugs.



Though ABC transporters are primarily associated with drug resistance, the researchers report an association between some of these proteins and an increase in effectiveness of some cancer drugs. Their database should serve as a starting point for research into novel therapies designed either to evade or exploit the action of ABC transporters.

ABC transport proteins are embedded in the cell membrane and regulate traffic of many molecules, including hormones, lipids, and drugs, in and out of the cell. Because they transport toxic materials out of cells, many of these 48 proteins confer resistance to cancer drugs in humans. The study’s lead authors were Jean-Philippe Annereau, Ph.D., and Gergely Szakács, M.D., Ph.D., both visiting fellows at NCI’s Center for Cancer Research (CCR). Szakács said, "Multidrug resistance is a major barrier to effective cancer chemotherapy, and even low levels of resistance can have a significant impact on the efficacy of chemotherapy."


Though these proteins have major implications for the treatment of cancer, previous studies had characterized only 17 of them using much less sensitive techniques. Szakács and Annereau studied the ABC transporters in a group of cancer cell lines called the NCI-60 cells, which includes leukemias, melanomas, and ovarian, breast, prostate, lung, renal, and colon cancers.

They used real-time polymerase chain reaction to detect and quantify the expression of ABC transporter genes as messenger RNA in these cells. With help from collaborators in the laboratory of John Weinstein, M.D., Ph.D., also in CCR, the researchers found statistical correlations between tests of the cell lines’ sensitivity to cancer drugs and these cells’ expression of ABC transporters. Further tests, such as measuring changes in cell growth to evaluate the cells’ response to the drugs, supported the statistical correlations.

Analysis of 68,592 ABC gene and drug relationships yielded 131 strongly inverse-correlated pairs--that is, in these 131 cases, cells’ ABC gene expression was strongly correlated with decreased sensitivity to the drug. According to Michael Gottesman, M.D., one of the paper’s senior authors and chief of the Laboratory of Cell Biology in CCR, "These results indicate that some of the ABC transporters whose function remains unknown can influence the response of cells to cancer treatment."

Gottesman, Szakács, and colleagues hope this data will be used to find commonalities in compounds transported by MDR1, one of the ABC proteins most strongly associated with multidrug resistance. With this information, they could begin developing a drug to undermine MDR1’s ability to transport drugs out of the cell.

Expression of some ABC transporters, most notably MDR1, caused an increase in cancer cells’ sensitivity to some drugs. This increase was unexpected, as MDR1 is perhaps the best-known multidrug resistance protein. The researchers advocate further research in order to discover additional compounds that interact in this way with MDR1 and other ABC transporters.

NCI Press Officers | EurekAlert!
Further information:
http://www.nci.nih.gov
http://www.cancer.gov

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>