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Finding could aid fight against cancer, aging

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SUNCOAST NEWS STAFF REPORT

The Tampa Tribune

Published: September 24, 2008

If they new how to trigger cell death, doctors would have a powerful tool for fighting cancer. On the other hand, if they knew how to block cell death, they would have an equally powerful tool with which to battle the ravages of aging.

Researchers at the Wistar Institute think they have such a double-edged therapeutic sword in hand.

As they reported Aug. 31 in the online version of the journal Nature, scientist at the research center in Philadelphia have made an important discovery about molecular structure of telomerase. An enzyme, telomerase is thought to play a key role in the development of most human forms of cancer.

In people, telomerase adds multiple copies of a short sequence of DNA, the main element of the genetic code, to the ends of chromosomes. These structures, known as telomeres, prevent damage and the loss of genetic information during cell division.

There is little telomerase activity in normal adult cells but lots of it in most types of cancer cells.

As a result, telomerase would be an "ideal target for chemotherapy" because it should have no effect on noncancerous cells, says Emmanuel Skordalakes, assistant professor in Wistar's Gene Expression and Regulation Program. Skordalakes led the study published in Nature.

"That means a drug that deactivates telomerase would likely work against all cancers, with few side effects," Skordalakes says.

In the absence of telomerase the telomeres get shorter each times a cell divides and reproduces. Eventually the telomeres are used up, causing the cell to die. Scientists call this process of programmed cell death apoptosis.

Telomerase, however, protects cancer cells apoptosis and allows them to keep reproducing in the prolific, uncontrolled manner that characterizes malignancies.

Conversely, telomerase could form the basis of therapies to combat aging and age-related diseases. If they were to use telomerase in a controlled manner doctors could reactivate cell division, producing healthier, younger-looking tissue that lives longer.

Telomerase is a complex structure made up of multiple protein molecules and a piece of RNA. The enzyme uses the RNA, another genetic component of cells, to create the DNA that is added to telomeres.

Skordalakes and his colleagues have been studying the three-dimensional structure of Telomerase's active region. This catalytic component is called telomerase reverse transcriptase protein, or TERT.

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