Cold Spring Harbor, NY -- The enzyme telomerase has received a great deal of attention since 1998 when researchers showed that expressing this enzyme in human tissue culture cells significantly extended the life-span of the cells. Telomerase expression was immediately recognized as a useful strategy for growing the large number of cells required for cell-based therapeutic procedures. Now, however, scientists report that using telomerase to extend the life-span of human tissue culture cells is associated with activation of the c-myc oncogene and thus may present some level of cancer risk if the cells are intended for therapeutic use in humans.
David Beach, of the Wolfson Institute for Biomedical Research (University College London) and his colleagues reported these findings in the June 15 issue of Nature. Joining Beach in the study were Jing Wang of Genetica, Inc. (Cambridge, Massachusetts) and Gregory Hannon of Cold Spring Harbor Laboratory.
The ends of chromosomes, called telomeres, consist of specialized repeated sequences of DNA (TTAGGG in humans) that serve to maintain the integrity of the chromosome. In the absence of telomerase, telomeres shorten with each cell division. Eventually, cells stop dividing when they sense that their telomeres are too short to maintain chromosomal integrity. In contrast, telomerase maintains telomere length by adding nucleotides one at a time to existing chromosomal ends in a regulated fashion.
Experiments in other laboratories had indicated that the use of telomerase expression to extend the life-span of cultured cells did not appear to transform these cells into a hyperproliferative, cancerous state. Now, Beach and his colleagues have shown that at least one hallmark of cancer cells is observed in such cells, namely, activation of the c-myc oncogene.
Frequently, cells grown in culture--such as the human mammary epithelial cells (HMEC) used in this study--undergo 50 to 60 population doublings before
Contact: Peter W. Sherwood, Ph.D.
Cold Spring Harbor Laboratory