Scientists at the National Cancer Institute, 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.