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Molecular and Cellular Biology, June 2001, p. 3862-3875, Vol. 21, No. 12
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.12.3862-3875.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Coexistence of Alternative Lengthening of Telomeres and Telomerase in hTERT-Transfected GM847 Cells

Kilian Perrem, Lorel M. Colgin, Axel A. Neumann, Thomas R. Yeager, and Roger R. Reddel*

Cancer Research Group, Children's Medical Research Institute, Westmead, Sydney, New South Wales 2145, Australia

Received 1 November 2000/Returned for modification 7 December 2000/Accepted 26 March 2001

It has been shown previously that some immortalized human cells maintain their telomeres in the absence of significant levels of telomerase activity by a mechanism referred to as alternative lengthening of telomeres (ALT). Cells utilizing ALT have telomeres of very heterogeneous length, ranging from very short to very long. Here we report the effect of telomerase expression in the ALT cell line GM847. Expression of exogenous hTERT in GM847 (GM847/hTERT) cells resulted in lengthening of the shortest telomeres; this is the first evidence that expression of hTERT in ALT cells can induce telomerase that is active at the telomere. However, rapid fluctuation in telomere length still occurred in the GM847/hTERT cells after more than 100 population doublings. Very long telomeres and ALT-associated promyelocytic leukemia (PML) bodies continued to be generated, indicating that telomerase activity induced by exogenous hTERT did not abolish the ALT mechanism. In contrast, when the GM847 cell line was fused with two different telomerase-positive tumor cell lines, the ALT phenotype was repressed in each case. These hybrid cells were telomerase positive, and the telomeres decreased in length, very rapidly at first and then at the rate seen in telomerase-negative normal cells. Additionally, ALT-associated PML bodies disappeared. After the telomeres had shortened sufficiently, they were maintained at a stable length by telomerase. Together these data indicate that the telomerase-positive cells contain a factor that represses the ALT mechanism but that this factor is unlikely to be telomerase. Further, the transfection data indicate that ALT and telomerase can coexist in the same cells.

* Corresponding author. Mailing address: Children's Medical Research Institute, Locked Bag 23, Wentworthville, NSW 2145, Australia. Phone: 61 2 9687 2800. Fax: 61 2 9687 2120. E-mail: rreddel{at}cmri.usyd.edu.au.

Molecular and Cellular Biology, June 2001, p. 3862-3875, Vol. 21, No. 12
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.12.3862-3875.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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