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Tip
Sheet: Medical Science & Health Tip sheets highlight timely news and events at Washington University in St. Louis. For more information on any of the stories below or for assistance in arranging interviews, please see the contact information listed with each story. For comments on the Medical Science & Health news tips service, please contact the editor, Jim Dryden at (314) 286-0110 or drydenj@msnotes.wustl.edu. 'Immortality enzyme' may make cancer cells immune to therapy Media assistance: Darrell Ward - (314) 286-0122 [St. Louis, Mo., March 2003] - Research at Washington University School of Medicine in St. Louis has shown that an enzyme that allows cancer cells to divide endlessly in the laboratory also may help them resist radiation and chemotherapy. The study, published in the January issue of the journal Oncogene, investigated how the enzyme telomerase, which often is produced by cancer cells, attaches to chromosomes. Surprisingly, the findings also revealed that the enzyme might reduce the effectiveness of cancer therapy.
According to Pandita, several telomerase-inhibiting drugs currently are under development. Under normal conditions, telomerase is produced mainly by stem cells and by egg and sperm cells and their progenitors, where it adds repeating segments of DNA to the ends of chromosomes. These ends, known as telomeres, protect the chromosome's tips. In addition, they are believed to serve as a cell's biological clock. Each time a cell divides, the telomeres on its chromosomes become shorter. When they drop to a certain length, the cell stops dividing and gradually dies. Telomerase also is found in more than 80 percent of cancers. The enzyme helps cancer cells circumvent their biological clock by keeping their telomeres at a constant length, enabling the cells to divide indefinitely. Pandita and colleagues studied the gene for the catalytic subunit of human telomerase (hTERT) -- the part of the telomerase molecule that binds to telomeres -- into human cells. To their surprise, they discovered that the joining of telomerase to the telomeres is followed some 60 hours later by an increase and decrease in the activity of dozens of genes, many of which are related to cancer progression and resistance to cancer therapy. On one hand, it reduced that activity of genes involved in programmed cell death, or apoptosis. Programmed cell death causes the demise of cells damaged by radiation chemotherapy and radiation therapy. On the other hand, it increased the activity of genes involved in repairing damaged DNA. This triggered a greater increase in the repair of radiation-caused breaks in the DNA strand and removal of so-called DNA adducts, small molecules that damage DNA by clinging to it. Since radiation therapy works by breaking DNA strands, and many types of chemotherapy work by causing DNA adducts, the researchers concluded that telomerase helps cancer cells survive many of our most important forms of cancer therapy. Pandita now is studying ways to block the binding of telomerase to telomeres. Sharma GG, Gupta A, Wang H, Scherthan H, Dhar S, Gandhi V, Iliakis G, Shay JW, Young CSH, Pandita TK. hTERT associates with human telomeres and enhances genomic stability and DNA repair. Oncogene, 22, 131-146, January 2003. Funding from the National Institute Neurological Disorders and Stroke, the Department of Defense and the Ataxia-Telangiectasia Children's Society supported this research. |
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