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


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.


  1. 1

    Bodnar, A.G. et al. Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349– 352 (1998).

    CAS  Article  Google Scholar 

  2. 2

    Weinrich, S.L. et al. Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT. Nature Genet. 17, 498–502 (1997).

    CAS  Article  Google Scholar 

  3. 3

    McKay, B.S. & Burke, J.M. Separation of phenotypically distinct subpopulations of cultured human retinal pigment epithelial cells. Exp. Cell Res. 213, 85–92 (1994).

    CAS  Article  Google Scholar 

  4. 4

    Weinberg, R.A. The retinoblastoma protein and cell cycle control. Cell 81, 323–330 (1995).

    CAS  Article  Google Scholar 

  5. 5

    Alcorta, D.A. et al. Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc. Natl Acad. Sci. USA 93, 13742–13747 (1996).

    CAS  Article  Google Scholar 

  6. 6

    Linke, S.P., Clarkin, K.C., Di Leonardo, A., Tsou, A. & Wahl, G.M. A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage. Genes Dev. 10, 934– 947 (1996).

    CAS  Article  Google Scholar 

  7. 7

    Pedrali-Noy, G. et al. Synchronization of HeLa cell cultures by inhibition of DNA polymerase α with aphidicolin. Nucleic Acids Res. 8, 377–387 (1980).

    CAS  Article  Google Scholar 

  8. 8

    White, A.E., Livanos, E.M. & Tlsty, T.D. Differential disruption of genomic integrity and cell cycle regulation in normal human fibroblasts by the HPV oncoproteins. Genes Dev. 8, 666–677 ( 1994).

    CAS  Article  Google Scholar 

  9. 9

    Yin, Y., Tainsky, M.A., Bischoff, F.Z., Strong, L.C. & Wahl, G.M. Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell 70, 937–948 (1992).

    CAS  Article  Google Scholar 

  10. 10

    Livingstone, L.R. et al. Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell 70, 923–935 (1992).

    CAS  Article  Google Scholar 

  11. 11

    Schwartz, D., Almog, N., Peled, A., Goldfinger, N. & Rotter, V. Role of wild type p53 in the G2 phase: regulation of the γ-irradiation-induced delay and DNA repair. Oncogene 15, 2597–2607 ( 1997).

    CAS  Article  Google Scholar 

  12. 12

    Khan, S.H. & Wahl, G.M. p53 and pRb prevent rereplication in response to microtubule inhibitors by mediating a reversible G1 arrest. Cancer Res. 58, 396–401 (1998).

    CAS  PubMed  Google Scholar 

  13. 13

    Gualberto, A., Aldape, K., Kozakiewicz, K. & Tlsty, T.D. An oncogenic form of p53 confers a dominant, gain-of-function phenotype that disrupts spindle checkpoint control. Proc. Natl Acad. Sci. USA 95, 5166–5171 ( 1998).

    CAS  Article  Google Scholar 

  14. 14

    Freedman, V.H. & Shin, S.I. Cellular tumorigenicity in nude mice: correlation with cell growth in semi-solid medium. Cell 3, 355–359 ( 1974).

    CAS  Article  Google Scholar 

  15. 15

    Shin, S., Freedman, V.H., Risser, R. & Pollack, R. Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. Proc. Natl Acad. Sci. USA 72, 4435–4439 ( 1975).

    CAS  Article  Google Scholar 

  16. 16

    Saksela, E. & Moorhead, P.S. Aneuploidy in the degenerative phase of serial cultivation of human cell strains. Genetics 50, 390–395 (1963).

    CAS  Google Scholar 

  17. 17

    Benn, P.A. Specific chromosome aberrations in senescent fibroblast cell lines derived from human embryos. Am. J. Hum. Genet. 28, 465–473 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18

    Johnson, T.E. et al. Karyotypic and phenotypic changes during in vitro aging of human endothelial cells. J. Cell Physiol. 150, 17–27 (1992).

    CAS  Article  Google Scholar 

  19. 19

    Lee, H.W. et al. Essential role of mouse telomerase in highly proliferative organs. Nature 92, 569– 574 (1998).

    Article  Google Scholar 

  20. 20

    Wright, W.E., Piatyszek, M.A., Rainey, W.E., Byrd, W. & Shay, J.W. Telomerase activity in human germline and embryonic tissues and cells. Dev. Genet. 18, 173–179 (1996).

    CAS  Article  Google Scholar 

  21. 21

    Chiu, C.P. et al. Differential expression of telomerase activity in hematopoietic progenitors from adult human bone marrow. Stem Cells 14, 239–248 (1996).

    CAS  Article  Google Scholar 

  22. 22

    Mullen, P., Ritchie, A., Langdon, S.P. & Miller, W.R. Effect of matrigel on the tumorigenicity of human breast and ovarian carcinoma cell lines. Int. J. Cancer 67, 816– 820 (1996).

    CAS  Article  Google Scholar 

  23. 23

    Noel, A. et al. Enhancement of tumorigenicity of human breast adenocarcinoma cells in nude mice by matrigel and fibroblasts. Br. J. Cancer 68, 909–915 (1993).

    CAS  Article  Google Scholar 

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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).

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