Proliferation Potential
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By Alexandra Goho

Proliferation Potential

Researchers try to put the brakes on cancer cells’ growth and division

By Alexandra Goho


For most cells in our body, replication has its limits. A typical cell is allowed to divide anywhere from 50 to 90 times before the process comes to a halt. Cancer cells, however, don’t play by such rules.

Like a carefully cordoned-off blaze that suddenly bursts into a forest-leveling fire, cancer cells have figured out how to get around this barrier to their proliferation. This attribute, known as “limitless replicative potential,” allows cancer cells to multiply indefinitely. It’s a key hallmark of cancer—and one that researchers are learning to control with the hope of developing new therapies to treat the disease.
 

Keeping Telomeres Long

Cancer cells have two ways of achieving such immortality. The first involves manipulating the protective tips on the ends of their chromosomes, the structures in the cell nucleus that contain genetic material. These tips, called telomeres, consist of repetitive sequences of DNA that get slightly shorter with each round of cell division. Telomeres in most human cells progressively shorten over a person’s lifespan. When an individual reaches middle age, his or her telomeres in those cells are half as long as they were when that person was born. In essence, telomeres can act as molecular clocks, counting the number of times a cell divides. When telomeres reach a certain minimum length, a biochemical signal tells the cell to either stop growing altogether or commit suicide.

Cells can prevent the shortening of telomeres by producing an enzyme called telomerase. The enzyme adds DNA sequences to the ends of chromosomes—in effect, restocking the depleted ends. This signals the cell to continue multiplying. The majority of healthy cells in the body do not make telomerase. One exception is stem cells. These specialized cells are necessary for renewing blood and skin cells, as well as those lining the intestinal tract.

Not surprising, cancer cells also turn out telomerase.

Telomerase 

Cancer cells (brown abnormal cells) can continue to grow and divide when other cells would stop. One reason: In most of the body's cells, the chromosomes (blue), which are tightly packed molecules of DNA, shorten at their ends with each cell division. When those ends, called telomeres (bright blue), get too short, the cell stops growing or dies. But cancer cells produce an enzyme called telomerase (purple), which adds DNA sequences (TTAGGG) to the telomeres—preventing them from shortening. [Art: Nicolle Rager Fuller]

Telomerase was discovered in 1984 by molecular biologists Carol Greider, now at the Johns Hopkins University School of Medicine in Baltimore, and Elizabeth Blackburn, now at the University of California, San Francisco. At the time, the two were unaware of the enzyme’s role in cancer. It wasn’t until 1992 that Greider and her colleagues published research showing that, indeed, human cancer cells generate telomerase.

“But it’s not the presence of the enzyme telomerase that makes the cells immortal,” Greider clarifies. A combination of factors accounts for immortal growth in most cells, she says, including “the fact that the short telomeres are topped off.” And while up to 90 percent of cancer cells rely on telomerase to maintain telomere length, some cancer cells use a different tack: The cells swap bits of genetic material between the ends of their chromosomes during cell division. Researchers have found evidence of this alternate strategy in certain types of bone and brain cancer.



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