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UCSF scientists halt tumor growth by manipulating telomerase enzyme

UCSF researchers report that they were able to slow the growth of human cancer cells - or cause them to commit suicide altogether -- by creating just a miniscule mutation in the telomerase enzyme.

The study, conducted in breast and prostate cells grown in culture and in tumors formed from human breast cancer cells grafted into mice, suggests that human cancer cells are much more sensitive to disruptions in the telomerase enzyme than had been thought. The finding hints, the researchers say, at a possible new strategy for thwarting human cancers.

In humans, telomerase is inactive in most adult cells, and only active at certain times in others, but it is highly active in cancer cells, and has been suggested as a potential therapeutic target. However, previous studies in human cancer cells have indicated that disrupting telomerase as a means of halting cancer cell replication or inducing cell suicide would require an almost complete loss of normal telomerase activity. And this would require either swamping the enzyme with an overwhelming amount of mutant telomerase or finding a sufficiently potent drug to completely inhibit the enzyme.

But in the current study, the researchers observed that inserting a tiny mutation in the gene coding for a small but critical portion of the telomerase enzyme prompted a dramatic response from cancer cells. The finding suggests a more efficient means of delivering therapy. Most of the human breast and prostate cancer cells grown in culture lost the ability to replicate or they committed suicide, while tumors formed from human breast cancer cells grafted into mice were smaller than those generated from cells that didn't have the mutation. Moreover the response occurred despite the fact that most of the normal telomerase was retained. The researchers induced the response with several different variations of the mutant gene.

"We were quite surprised at how strong the effect was," says the senior author of
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
2-Jul-2001


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