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Molecular and Cellular Biology, March 1999, p. 1864-1870, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Telomerase Activity Is Sufficient To Allow Transformed Cells To Escape from Crisis

Tanya L. Halvorsen, Gil Leibowitz, and Fred Levine*

Center for Molecular Genetics, University of California at San Diego, La Jolla, California 92093-0634

Received 20 July 1998/Returned for modification 28 August 1998/Accepted 23 November 1998

The introduction of simian virus 40 large T antigen (SVLT) into human primary cells enables them to proliferate beyond their normal replicative life span. In most cases, this temporary escape from senescence eventually ends in a second proliferative block known as "crisis," during which the cells cease growing or die. Rare immortalization events in which cells escape crisis are frequently correlated with the presence of telomerase activity. We tested the hypothesis that telomerase activation is the critical step in the immortalization process by studying the effects of telomerase activity in two mortal SVLT-Rasval12-transformed human pancreatic cell lines, TRM-6 and beta lox5. The telomerase catalytic subunit, hTRT, was introduced into late-passage cells via retroviral gene transfer. Telomerase activity was successfully induced in infected cells, as demonstrated by a telomerase repeat amplification protocol assay. In each of nine independent infections, telomerase-positive cells formed rapidly dividing cell lines while control cells entered crisis. Telomere lengths initially increased, but telomeres were then maintained at their new lengths for at least 20 population doublings. These results demonstrate that telomerase activity is sufficient to enable transformed cells to escape crisis and that telomere elongation in these cells occurs in a tightly regulated manner.

* Corresponding author. Mailing address: University of California, San Diego, Center for Molecular Genetics, Rm. 122, La Jolla, CA 92093-0634. Phone: (619) 534-5979. Fax: (619) 534-1422. E-mail: flevine{at}ucsd.edu.

Molecular and Cellular Biology, March 1999, p. 1864-1870, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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Copyright © 1999 by the American Society for Microbiology. All rights reserved.