"The telomerase enzyme is an ideal target for chemotherapy because this enzyme is active in about 90 percent of human tumors, but inactive in most normal cells," Dr. Weinberg says. "Pharmaceutical companies have screened thousands of compounds to find agents capable of blocking telomerase. Now that we know the identity of the catalytic subunit, drug development should move much faster."
Dr. Weinberg, principal authors Drs. Matthew Meyerson and Christopher Counter, and their colleagues from the Whitehead Institute, the Massachusetts Institute of Technology, Massachusetts General Hospital, Merck Research Laboratories, and McMaster University in Ontario, Canada, describe the new telomerase subunit gene, hEST2 (human Ever Shorter Telomeres 2), in the August 22 issue of Cell magazine. They report that this telomerase gene is expressed at high levels in primary human tumors (11 of 11 tumor samples studied, including 2 breast tumors and 4 ovarian tumors), but undetectable in most normal human tissues, including breast, ovary, heart, brain, placenta, liver, skeletal muscle and prostate.
The normal function of telomerase in the body is to help maintain the ends of chromosomes in reproductive cells (cells that produce eggs and sperm) and in certain immature progenitor cells that give rise to other body tissues. Telomerase activity is not detectable in most mature cells.
Switching off telomerase during development can be likened to setting a
Contact: Eve Nichols or Seema Kumar
Whitehead Institute for Biomedical Research