RESTORATION OF THE CELLULAR SENESCENCE PROGRAM AND REPRESSION OF TELOMERASE BY HUMAN-CHROMOSOME-3

Telomeres, at the end of chromosomes, shorten with each cell division, resulting in cellular senescence. Tumor cells, unlike normal somatic cells, express a telomerase that maintains the telomere length. Deleti on of a gene(s) on chromosome 3 is common in human renal cell carcinom a (RCC) and reintroduction of a normal chromosome 3 into an RCC immort al cell line restored the program of cellular senescence. The loss of indefinite growth potential was associated with the loss of telomerase activity and shortening of telomeres in the RCC cells with a normal c hromosome 3. However, microcell hybrids that escaped from senescence a nd microcell hybrids with an introduced chromosome 7 or 11 maintained telomere lengths and telomerase activity similar to those of the paren tal RCC23. Thus, restoration of the cellular senescence program by chr omosome 3 is associated with repression of telomerase function in RCC cells.