Featured Research

from universities, journals, and other organizations

Scientists Establish Database Of Genes Associated With Cancer Drug Resistance

Date:
August 26, 2004
Source:
NIH/National Cancer Institute
Summary:
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.

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 22, 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 to either 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 the 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. Michael Gottesman, M.D., one of the paper’s senior authors and chief of the Laboratory of Cell Biology in CCR, said, “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 even more compounds that interact in this way with MDR1 and other ABC transporters. For more information about cancer, please go to http://cancer.gov.

###

* Szakács G and Gottesman MM. "Predicting drug sensitivity and resistance: Profiling ABC transporter genes in cancer cells." Cancer Cell. 22 August 2004.


Story Source:

The above story is based on materials provided by NIH/National Cancer Institute. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Cancer Institute. "Scientists Establish Database Of Genes Associated With Cancer Drug Resistance." ScienceDaily. ScienceDaily, 26 August 2004. <www.sciencedaily.com/releases/2004/08/040825092629.htm>.
NIH/National Cancer Institute. (2004, August 26). Scientists Establish Database Of Genes Associated With Cancer Drug Resistance. ScienceDaily. Retrieved April 18, 2014 from www.sciencedaily.com/releases/2004/08/040825092629.htm
NIH/National Cancer Institute. "Scientists Establish Database Of Genes Associated With Cancer Drug Resistance." ScienceDaily. www.sciencedaily.com/releases/2004/08/040825092629.htm (accessed April 18, 2014).

Share This



More Health & Medicine News

Friday, April 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) — The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com
Obama: 8 Million Healthcare Signups

Obama: 8 Million Healthcare Signups

AP (Apr. 17, 2014) — President Barack Obama gave a briefing Thursday announcing 8 million people have signed up under the Affordable Care Act. He blasted continued Republican efforts to repeal the law. (April 17) Video provided by AP
Powered by NewsLook.com
Is Apathy A Sign Of A Shrinking Brain?

Is Apathy A Sign Of A Shrinking Brain?

Newsy (Apr. 17, 2014) — A recent study links apathetic feelings to a smaller brain. Researchers say the results indicate a need for apathy screening for at-risk seniors. Video provided by Newsy
Powered by NewsLook.com
Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) — A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. 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