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Stanford researchers unmask proteins in telomerase, a substance that enables cancer
Date:3/20/2008

. After a lifetime of cells dividing, the telomeres dwindle down to a length that eventually triggers the cell to stop replicating altogether or die.

Cancerous cells overcome that lifespan limitation by making telomerase, which repairs those snipped chromosome ends. Without shortening, the cells can divide forever. Telomerase is normally active in fetal cells, then shortly after birth it is turned off in all cells except normal tissue stem cells and some immune cells.

Since telomerase's discovery in cancerous cells in 1994, the idea has been that if a drug could block telomerase, chromosomes in those cancerous cells would eventually grow shorter and the cells would age and die just like any other cell in the body. But without knowing what proteins make up telomerase it's hard to design a drug to block it.

In the study, Artandi and first author Andrew Veneicher, an MD/PhD student, describe two protein components of telomerase. They also show that disabling one of the proteins brings telomerase to a grinding halt. Although the work was done in cells in a lab dish, the findings suggest that a drug blocking that protein may be a useful tool against cancer.

Artandi said one problem with studying telomerase is that it's available in such small quantities. Growing huge vats of cancer cells in the lab still only results in miniscule amounts of protein. Until recently, no technology was sensitive enough to analyze proteins at such minute levels.

"Many technical advances feed into our ability to make this discovery," Artandi said.

Artandi and his colleagues at the National Cancer Institute and Washington University School of Medicine took advantage of new technologies to get around the quantity problem. They chopped the massive telomerase complex into tiny protein pieces, then sent those pieces through a sensitive device that detected the pieces and compared the protein sequence to a genetic database that could match the
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Contact: Amy Adams
650-723-3900
Stanford University Medical Center
Source:Eurekalert

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