"Cell Biology: Risky Immortalization
Jing Wang, Gregory J. Hannon, and David H. Beach,
Nature, Vol. 405, pp. 755 - 756 (June 15, 2000).
Senescence naturally limits the proliferation of mammalian cells in culture, possibly by shortening the telomere regions at the ends of chromosomes during cell division. In support of this idea, introducing TERT, the catalytic subunit of telomerase the enzyme that maintains chromosome ends into certain cell types can extend their lifespan and potentially immortalize them. It has been proposed that treatment with exogenous TERT might be useful for cell-based therapies by allowing indefinite expansion of normal human cells without damaging their genomes. But we show here that TERT-driven cell proliferation is not genoprotective because it is associated with activation of the c-myc oncogene.
Treatment, Cancer Linked
AP Science Writer
June 15, 2000 (AP) -- A new study reported in Nature suggests that an experimental lab technique for growing cells for transplant into patients may activate a gene that is known to promote cancer. The technique uses an enzyme, called telomerase, which has been called a potential "fountain of youth" for cells. Telomerase made headlines in 1998, when researchers reported that it allowed human cells to remain young and continue to divide indefinitely.
Speculation that telomerase might also be used to keep people young captured public attention, but the scientific focus has largely been elsewhere. For example, researchers have been hoping to use telomerase to treat conditions like diabetes or liver disease. They envision taking tissue from a patient and using the enzyme to build up a population of rejuvenated cells that could be implanted in the patient. That idea has been shadowed by concerns that such a treatment might promote cancer, even after other research in 1998 found no evidence for that connection.
The new result doesn't mean scientists should abandon hopes for telomerase, said study author Prof. David Beach of University College London, UK. Instead, he said, it suggests the enzyme isn't the whole answer. Beach and two colleagues in the United States present their work in Thursday's issue of the journal Nature. The researchers worked with human breast cells. After they inserted a gene to make the cells produce telomerase, and the cells were grown in a lab, scientists found the cells had activated a gene called "c-myc." This gene is active in a wide variety of cancers. The cells in the experiment were not cancerous, but they had "moved one step closer to becoming tumor cells," Beach said. "That suggests a risk of cancer if telomerase-treated cells were ever used in therapy," he said. So "we have got to do a bit more biology" to overcome that problem, he said. Telomerase itself apparently didn't switch on the gene. Instead, the prolonged cell life in the lab apparently set the stage for the gene to be turned on by something else.
Prof. Jerry Shay of the University of Texas Southwestern Medical Center in Dallas, an author of the original 1998 study, said he had not seen the cancer gene activated in other kinds of cells treated with telomerase. "Whether the gene gets turned on or not may depend on what kind of cell is under study," he said.