Discovery of a clever trick that cancer cells use to make themselves immortal may lead to a way to stop their unchecked growth, according to scientists at the University of California, Berkeley.

In a paper published in the journal Nature Cell Biology, UC Berkeley molecular biologists describe a significant difference between the way normal and cancerous cells handle an enzyme called telomerase, which is critical to unrestricted cell growth. The enzyme maintains the telomeres that cap the ends of each chromosome, keeping them long enough so that DNA replication and cell division go without a hitch.

When a cell's telomeres get too short and are not properly tied up, division stops.

Post-doctoral fellow Judy M. Y. Wong and associate professor Kathleen Collins discovered that telomerase is walled off from the chromosomes of normal cells until needed, and is then released into the DNA-rich area of the nucleus to touch up the telomeres, which shorten somewhat with each cell division. The enzyme is then shuttled back to its compartment, called the nucleolus, to await the next round of division.

Cancer cells, on the other hand, have found a way to mobilize telomerase continually so they can quickly double and redouble while keeping the telomeres intact. Some cancer cell lines in use today have been growing for almost half a century, their telomeres kept long and healthy by the readily available telomerase.

"Normal somatic cells keep most of the telomerase away from the DNA, whereas cancer cells let all of it go," said Collins, a member of the Department of Molecular & Cell Biology. "This should help the transformed (cancer) cells use telomerase much more efficiently."

Though Wong and Collins have yet to discover how cancer cells mobilize telomerase, finding a way to round them up again could stop the unbridled growth of cancer cells. They now are searching for the proteins and signals involved in telomerase shuttling around the cell nucleus.

An alternative approach taken by most telomerase researchers and a number of biotech firms is to search for ways to turn off telomerase to stop cancerous growth.

The UC Berkeley researchers also see a potential medical benefit in boosting telomerase in patients receiving chemotherapy, or in people with HIV who experience continual, rapid turnover of immune cells, which exhausts the limited number of divisions allotted to immune cells.

"Activation of telomerase, perhaps by gene therapy, could have a lot of benefit for these people," Collins said. "Combining telomerase activation with chemotherapy is an approach we would like to try."

SOURCES:
Nature Cell Biology, September 2002
University of California, Berkeley (http://www.berkeley.edu)