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Telomerase expression in human somatic cells does not induce changes associated with a transformed phenotype

Abstract

Expression of the human telomerase catalytic component, hTERT, in normal human somatic cells can reconstitute telomerase activity and extend their replicative lifespan1,2. We report here that at twice the normal number of population doublings, telomerase-expressing human skin fibroblasts (BJ-hTERT) and retinal pigment epithelial cells (RPE-hTERT) retain normal growth control in response to serum deprivation, high cell density, G1 or G2 phase blockers and spindle inhibitors. In addition, we observed no cell growth in soft agar and detected no tumour formation in vivo. Thus, we find that telomerase expression in normal cells does not appear to induce changes associated with a malignant phenotype.

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Figure 1: Expression of pRb and p16 as a function of cell density.
Figure 2: TERT-expressing clones arrest appropriately in response to G1/S blockers.
Figure 3: hTERT clones undergo normal growth arrest in response to PALA and γ-irradiation.
Figure 4: hTERT clones arrest appropriately in response to the spindle inhibitor colcemid.

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Acknowledgements

We thank C. Harley and T. Okarma for critical reading of the manuscript and A. Bronstein and S. Starr for expert technical assistance. G.J. is supported by a postdoctoral fellowship from NIH. G.M.W. and M.B. are supported by grants from the NIH (CA 61449) and the G. Harold and Leila Y. Mathers Charitable Foundation. T.D.T. and M.S. are supported by grants from the NIH (CA 42765, CA 51912 and CA 58207).

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Correspondence to Choy-Pik Chiu.

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Jiang, XR., Jimenez, G., Chang, E. et al. Telomerase expression in human somatic cells does not induce changes associated with a transformed phenotype. Nat Genet 21, 111–114 (1999). https://doi.org/10.1038/5056

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