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 Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland

nachricht Protein involved in nematode stress response identified
14.12.2018 | University of Illinois College of Agricultural, Consumer and Environmental Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Data use draining your battery? Tiny device to speed up memory while also saving power

14.12.2018 | Power and Electrical Engineering

Tangled magnetic fields power cosmic particle accelerators

14.12.2018 | Physics and Astronomy

In search of missing worlds, Hubble finds a fast evaporating exoplanet

14.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>