The establishment of telomerase-immortalized cell lines representing humanchromosome instability syndromes

The limited life span of normal human cells represents a substantial obstac le for biochemical analysis, genetic manipulation and genetic screens. To o vercome this technical barrier, immortal human cell lines are often derived from tumors or produced by transformation with viral oncogenes such as SV4 0 large T antigen. Cell lines produced by these approaches are invariably t ransformed, genomically unstable and display cellular properties that diffe r from their normal counterpart. It was recently shown that the ectopic exp ression of hTERT, encoding the catalytic subunit of human telomerase, can e xtend the life span of normal human cells without causing cellular transfor mation and genomic instability. In the present study, we have used hTERT to extend the life span of normal human skin fibroblasts derived from patient s afflicted with syndromes of genomic instability and/or premature aging. O ur results show that hTERT efficiently extends the life span without alteri ng the characteristic phenotypic properties of the cells. Thus, the ectopic expression of telomerase represents a major improvement over the use of vi ral oncogenes for the establishment of human cell tines.