Cervical cancer warning sign

Like a bit player in a Broadway production, the enzyme telomerase is rarely seen in the healthy human body. In cancer patients, however, it often steals the show, performing a molecular sleight-of-hand that lets cell growth run amok.

Now, growing evidence shows that this tendency to hog the limelight may make telomerase an ideal warning of the cancers it seems to foster.

Recent studies in Germany and Japan offer the hope that bladder cancer can someday be detected with only a urine test for telomerase. In women with cervical cancer, the enzyme has shown up in samples taken with cotton swabs from the cervix, making telomerase a possible marker for that disease as well.

The studies follow a flood of basic research in the past decade linking telomerase to cancer (SN: 11/25/95, p. 362). The search for the means by which cancer cells divide unchecked often leads back to telomeres, tiny structures on the ends of chromosomes.

Like the plastic tips on the ends of shoelaces, telomeres stabilize chromosomes and keep them from fraying, says Jerry Shay, a researcher at the University of Texas Southwestern Medical Center at Dallas. Each time a cell divides, however, telomeres shorten. Eventually, the telomeres become small and the cell stops reproducing.

Telomerase, comprising RNA and proteins, keeps telomeres from shortening. Normally, the enzyme plays that role while an embryo is forming and cells are dividing frequently. In fact, it's rarely active in adults except in tumors, which can be rife with telomerase. How cancer cells trigger telomerase production is still unknown.

"That's the million-dollar question," says Shay.

Meanwhile, researchers in Germany are solidifying the cancer-telomerase connection. They found the enzyme in 29 of 40 bladder cancer patients given a bladder washing, a diagnostic procedure in which a catheter is inserted into the bladder, saline solution is pumped in, and the solution and urine are withdrawn together. Markus Muller of Freie University in Berlin reported the results on April 13 at the American Urological Conference in New Orleans.

Scientists in Japan report that of the 45 bladder cancer patients they tested, 36 exhibited telomerase in a bladder washing and more than half had the enzyme in a urine sample. Combined, the two procedures flagged telomerase in 40 of the patients, Hidefumi Kinoshita and his colleagues at Kyoto University report in the May 21 Journal of the National Cancer Institute. Bladder washings from 12 patients without cancer showed no telomerase.

In a separate study, researchers at Kanazawa University in Japan examined 82 women, including 17 who had cervical cancer and 32 with a precancerous condition. Telomerase showed up in samples taken with cotton swabs from 15 of the cancer patients and 19 of the precancerous patients; it appeared in only 3 of 33 healthy patients, the researchers report in the May 15 Cancer Research.

"More and more, these types of research studies show really promising potential for telomerase activity measurement in detecting cancer," says Calvin Harley, chief scientific officer at Geron Corp. in Menlo Park, Calif. Nam Kim, a staff scientist at Geron, devised the inexpensive laboratory technique now commonly used to detect telomerase.

The technique has spawned dozens of studies in the past 3 years, says Shay. Researchers are investigating the presence of telomerase as a marker for prostate, breast, lung, and colorectal cancers.

Ideally, researchers would like to have a simple technique to detect telomerase, such as a urine test. Patients object less to such noninvasive tests, Shay says.