Cancer cell's fountain of youth.

Even with failed brakes, a car eventually comes to a halt, if only because it runs out of gas. Likewise, cancer cells, which replicate continuously because of failed "brakes" on the cell cycle, should eventually stop dividing. They don't, however, because they also begin making an enzyme that helps them keep going, says Calvin B. Harley, a biochemist at McMaster University in Hamilton, Ontario.

Recently, other researchers demonstrated that cells multiply out of control when proteins that prevent replication don't do their job (SN: 4/23/94, p.262).

That alone shouldn't lead to cancer, says Huber R. Warner, a biochemist at the National Institute on Aging in Bethesda, Md. Normally, every time a cell duplicates its genes, it loses bits of extra DNA from the tips of its chromosomes. Those tips, called telomeres, seem to stabilize the chromosome. After many generations, when the tip is almost used up, the cells lose the ability to make accurate copies of their genes, stop replicating, age, and die.

Cancer cells avoid losing their telomeres by making an enzyme called telomerase. That enzyme replaces lost bits of DNA, making the cell immortal, Harley and his colleagues reported in the April 12 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES.

"Telomerase allows [the cell] to escape whatever normal controls there are on replication," says Warner.

Researchers had thought telomerase existed only in normal reproductive tissues, such as the cells that generate sperm. But McMaster's Christopher M. Counter and his colleagues found telomerase in cells removed from ovarian tumors as well.

The telomeres were shorter in the cancer cells than in cells from noncancerous ovarian tissue. But the scientists found that before the telomeres got too short to support faithful replication, the cells began making telomerase. Consequently, the researchers suspect that the progressive destabilization of chromosomes may lead to mutations. These changes result in the activation of the gene for telomerase, turning on this molecular fountain of youth in most, if not all, types of tumors.

Harley, now temporarily at Geron Corp. in Menlo Park, Calif., hopes to develop drugs that block the action of telomerase, thereby causing cancer cells to "run out of gas."