Telomerase contributes to tumorigenesis by a telomere length-independent mechanism

Sheila A. Stewart, William C. Hahn, Benjamin F. O'Connor, Elisa N. Banner, Ante S. Lundberg, Poonam Modha, Hana Mizuno, Mary W. Brooks, Mark Fleming, Drazen B. Zimonjic, Nicholas C. Popescu, Robert A. Weinberg

Research output: Contribution to journalArticlepeer-review

373 Scopus citations


Once immortalized, human cells are susceptible to transformation by introduction of an oncogene such as ras. Several lines of evidence now suggest that the maintenance of telomere length is a major determinant of replicative lifespan in human cells and thus of the immortalized state. The majority of human tumor cells acquire immortality through expression of the catalytic subunit of telomerase (hTERT), whereas others activate an alternative mechanism of telomere maintenance (ALT) that does not depend on the actions of telomerase. We have examined whether ALT could substitute for telomerase in the processes of transformation in vitro and tumorigenesis in vivo. Expression of oncogenic H-Ras in the immortal ALT cell line GM847 did not result in their transformation. However, subsequent ectopic expression of hTERT in these cells imparted a tumorigenic phenotype. Indeed, this outcome was also observed after introduction of a mutant hTERT that retained catalytic activity but was incapable of maintaining telomere length. These studies indicate that hTERT confers an additional function that is required for tumorigenesis but does not depend on its ability to maintain telomeres.

Original languageEnglish
Pages (from-to)12606-12611
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number20
StatePublished - Oct 1 2002


Dive into the research topics of 'Telomerase contributes to tumorigenesis by a telomere length-independent mechanism'. Together they form a unique fingerprint.

Cite this