The establishment of telomerase-immortalized cell lines representing human chromosome instability syndromes

The limited life span of normal human cells represents a substantial obstacle for biochemical analysis, genetic manipulation and genetic screens. To overcome this technical barrier, immortal human cell lines are often derived from tumors or produced by transformation with viral oncogenes such as SV40 large T antigen. Cell lines produced by these approaches are invariably transformed, genomically unstable and display cellular properties that differ from their normal counterpart. It was recently shown that the ectopic expression of hTERT, encoding the catalytic subunit of human telomerase, can extend the life span of normal human cells without causing cellular transformation and genomic instability. In the present study, we have used hTERT to extend the life span of normal human skin fibroblasts derived from patients afflicted with syndromes of genomic instability and/or premature aging. Our results show that hTERT efficiently extends the life span without altering the characteristic phenotypic properties of the cells. Thus, the ectopic expression of telomerase represents a major improvement over the use of viral oncogenes for the establishment of human cell tines.