{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:39:54Z","timestamp":1779345594901,"version":"3.51.4"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2000,8,1]],"date-time":"2000-08-01T00:00:00Z","timestamp":965088000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2000,8]]},"DOI":"10.1038\/78592","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T08:34:58Z","timestamp":1027672498000},"page":"849-851","source":"Crossref","is-referenced-by-count":324,"title":["Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology"],"prefix":"10.1038","volume":"6","author":[{"given":"Woodring E.","family":"Wright","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerry W.","family":"Shay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","reference":[{"key":"BFnm0800_849_CR1","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/0014-4827(61)90192-6","volume":"25","author":"L Hayflick","year":"1961","unstructured":"Hayflick, L. & Moorhead, P.S. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 25, 585\u2013621 (1961).","journal-title":"Exp. Cell Res."},{"key":"BFnm0800_849_CR2","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/0531-5565(92)90069-C","volume":"27","author":"WE Wright","year":"1992","unstructured":"Wright, W.E. & Shay, J.W. The two-stage mechanism controlling cellular senescence and immortalization. Exp. Gerontol. 27, 383\u2013389 (1992).","journal-title":"Exp. Gerontol."},{"key":"BFnm0800_849_CR3","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/0921-8734(91)90018-7","volume":"256","author":"CB Harley","year":"1991","unstructured":"Harley, C.B. Telomere loss: mitotic clock or genetic time bomb? Mutat. Res. 256, 271\u2013282 (1991).","journal-title":"Mutat. Res."},{"key":"BFnm0800_849_CR4","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0014-4827(91)90453-2","volume":"196","author":"JW Shay","year":"1991","unstructured":"Shay, J.W., Pereira-Smith, O.M. & Wright, W.E. A role for both RB and p53 in the regulation of human cellular senescence. Exp. Cell Res. 196, 33\u201339 (1991).","journal-title":"Exp. Cell Res."},{"key":"BFnm0800_849_CR5","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1016\/0006-291X(91)91403-Y","volume":"179","author":"E Hara","year":"1991","unstructured":"Hara, E., Tsurui, H., Shinozaki, A., Nakada, S. & Oda, K. Cooperative effect of antisense-Rb and antisense-p53 oligomers on the extension of life span in human diploid fibroblasts, TIG-1. Biochem. Biophys. Res. Commun. 179, 528\u2013534 (1991).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"BFnm0800_849_CR6","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1126\/science.279.5349.349","volume":"279","author":"AG Bodnar","year":"1998","unstructured":"Bodnar, A.G. et al. Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349\u2013352 (1998).","journal-title":"Science"},{"key":"BFnm0800_849_CR7","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0960-9822(98)70109-5","volume":"8","author":"H Vaziri","year":"1998","unstructured":"Vaziri, H. & Benchimol, S. Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. Curr. Biol. 8, 279\u2013282 (1998).","journal-title":"Curr. Biol."},{"key":"BFnm0800_849_CR8","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1002\/j.1460-2075.1996.tb00519.x","volume":"15","author":"WE Wright","year":"1996","unstructured":"Wright, W.E., Brasiskyte, D., Piatyszek, M.A. & Shay, J.W. Experimental elongation of telomeres extends the lifespan of immortal \u00d7 normal cell hybrids. EMBO J. 15, 1734\u20131741 (1996).","journal-title":"EMBO J."},{"key":"BFnm0800_849_CR9","doi-asserted-by":"publisher","first-page":"14723","DOI":"10.1073\/pnas.95.25.14723","volume":"95","author":"CM Counter","year":"1998","unstructured":"Counter, C.M. et al. Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization. Proc. Natl. Acad. Sci. USA 95, 14723\u201314728 (1998).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm0800_849_CR10","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1128\/MCB.19.3.1864","volume":"19","author":"TL Halvorsen","year":"1999","unstructured":"Halvorsen, T.L., Leibowitz, G. & Levine, F. Telomerase activity is sufficient to allow transformed cells to escape from crisis. Mol. Cell. Biol. 19, 1864\u20131870 (1999).","journal-title":"Mol. Cell. Biol."},{"key":"BFnm0800_849_CR11","doi-asserted-by":"publisher","first-page":"3723","DOI":"10.1073\/pnas.96.7.3723","volume":"96","author":"J Zhu","year":"1999","unstructured":"Zhu, J., Wang, H., Bishop, J.M. & Blackburn, E.H. Telomerase extends the lifespan of virus-transformed human cells without net telomere lengthening. Proc. Natl. Acad. Sci. USA 96, 3723\u20133728 (1999).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm0800_849_CR12","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S0092-8674(01)80006-4","volume":"91","author":"MA Blasco","year":"1997","unstructured":"Blasco, M.A. et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25\u201334 (1997).","journal-title":"Cell"},{"key":"BFnm0800_849_CR13","doi-asserted-by":"publisher","first-page":"5800","DOI":"10.1128\/MCB.15.10.5800","volume":"15","author":"J Zalvide","year":"1995","unstructured":"Zalvide, J. & DeCaprio, J.A. Role of pRb-related proteins in simian virus 40 large-T-antigen-mediated transformation. Mol. Cell. Biol. 15, 5800\u20135810 (1995).","journal-title":"Mol. Cell. Biol."},{"key":"BFnm0800_849_CR14","first-page":"2464","volume":"59","author":"T Kamijo","year":"1999","unstructured":"Kamijo, T. et al. Loss of the ARF tumor suppressor reverses premature replicative arrest but not radiation hypersensitivity arising from disabled atm function. Cancer Res. 59, 2464\u20132469 (1999).","journal-title":"Cancer Res."},{"key":"BFnm0800_849_CR15","doi-asserted-by":"publisher","first-page":"2984","DOI":"10.1101\/gad.12.19.2984","volume":"12","author":"CJ Sherr","year":"1998","unstructured":"Sherr, C.J. Tumor surveillance via the ARF-p53 pathway. Genes Dev. 12, 2984\u20132991 (1998).","journal-title":"Genes Dev."},{"key":"BFnm0800_849_CR16","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1038\/sj.onc.1201862","volume":"16","author":"SJ Robles","year":"1998","unstructured":"Robles, S.J. & Adami, G.R. Agents that cause DNA double strand breaks lead to p16INK4a enrichment and the premature senescence of normal fibroblasts. Oncogene 16, 1113\u20131123 (1998).","journal-title":"Oncogene"},{"key":"BFnm0800_849_CR17","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/S0092-8674(00)81902-9","volume":"88","author":"M Serrano","year":"1997","unstructured":"Serrano, M., Lin, A.W., McCurrach, M.E., Beach, D. & Lowe, S.W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593\u2013602 (1997).","journal-title":"Cell"},{"key":"BFnm0800_849_CR18","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1101\/gad.12.19.2997","volume":"12","author":"J Zhu","year":"1998","unstructured":"Zhu, J., Woods, D., McMahon, M. & Bishop, J.M. Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev. 12, 2997\u20133007 (1998).","journal-title":"Genes Dev."},{"key":"BFnm0800_849_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0047-6374(97)00067-5","volume":"98","author":"H Rubin","year":"1997","unstructured":"Rubin, H. Cell aging in vivo and in vitro. Mech. Ageing Dev. 98, 1\u201335 (1997).","journal-title":"Mech. Ageing Dev."},{"key":"BFnm0800_849_CR20","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1126\/science.3494308","volume":"236","author":"DT Loo","year":"1987","unstructured":"Loo, D.T., Fuquay, J.I., Rawson, C.L. & Barnes, D.W. Extended culture of mouse embryo cells without senescence: inhibition by serum. Science 236, 200\u2013202 (1987).","journal-title":"Science"},{"key":"BFnm0800_849_CR21","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/382551a0","volume":"382","author":"A Nussenzweig","year":"1996","unstructured":"Nussenzweig, A. et al. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature 382, 551\u2013555 (1996).","journal-title":"Nature"},{"key":"BFnm0800_849_CR22","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/S0092-8674(00)80086-0","volume":"86","author":"C Barlow","year":"1996","unstructured":"Barlow, C. et al. Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell 86, 159\u2013171 (1996).","journal-title":"Cell"},{"key":"BFnm0800_849_CR23","doi-asserted-by":"publisher","first-page":"2401","DOI":"10.1101\/gad.10.19.2401","volume":"10","author":"Y Xu","year":"1996","unstructured":"Xu, Y. & Baltimore, D. Dual roles of ATM in the cellular response to radiation and in cell growth control. Genes Dev. 10, 2401\u20132410 (1996).","journal-title":"Genes Dev."},{"key":"BFnm0800_849_CR24","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/ng1297-423","volume":"17","author":"F Connor","year":"1997","unstructured":"Connor, F. et al. Tumorigenesis and a DNA repair defect in mice with a truncating Brca2 mutation. Nature Genet. 17, 423\u2013430 (1997).","journal-title":"Nature Genet."},{"key":"BFnm0800_849_CR25","first-page":"1664","volume":"57","author":"CH Westphal","year":"1997","unstructured":"Westphal, C.H. et al. Genetic interactions between atm and p53 influence cellular proliferation and irradiation-induced cell cycle checkpoints. Cancer Res. 57, 1664\u20131667 (1997).","journal-title":"Cancer Res."},{"key":"BFnm0800_849_CR26","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/S0092-8674(00)80762-X","volume":"97","author":"L Chin","year":"1999","unstructured":"Chin, L. et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97, 527\u2013538 (1999).","journal-title":"Cell"},{"key":"BFnm0800_849_CR27","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/S0092-8674(00)80761-8","volume":"97","author":"RA Greenberg","year":"1999","unstructured":"Greenberg, R.A. et al. Short dysfunctional telomeres impair tumorigenesis in the INK4a(delta2\/3) cancer-prone mouse. Cell 97, 515\u2013525 (1999).","journal-title":"Cell"},{"key":"BFnm0800_849_CR28","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/0014-4827(89)90369-8","volume":"184","author":"JW Shay","year":"1989","unstructured":"Shay, J.W. & Wright, W.E. Quantitation of the frequency of immortalization of normal human diploid fibroblasts by SV40 large T-antigen. Exp. Cell Res. 184, 109\u2013118 (1989).","journal-title":"Exp. Cell Res."},{"key":"BFnm0800_849_CR29","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1006\/excr.1993.1283","volume":"209","author":"JW Shay","year":"1993","unstructured":"Shay, J. W., Van der Haegen, B. A., Ying, Y. & Wright, W. E. The frequency of immortalization of human fibroblast and mammary epithelial cells transfected with SV40 large T-antigen. Exp. Cell Res. 209, 45\u201352 (1993).","journal-title":"Exp. Cell Res."},{"key":"BFnm0800_849_CR30","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/23962","volume":"396","author":"T Kiyono","year":"1998","unstructured":"Kiyono, T. et al. Both Rb\/p16ink4a inactivation and telomerase activity are required to immortalize human epithelial cells. Nature 396, 84\u201388 (1998).","journal-title":"Nature"},{"key":"BFnm0800_849_CR31","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1128\/MCB.15.1.425","volume":"15","author":"JW Shay","year":"1995","unstructured":"Shay, J. W., Tomlinson, G., Piatyszek, M. A. & Gollahon, L. S. Spontaneous in vitro immortalization of breast epithelial cells from a Li-Fraumeni patient. Mol. Cell. Biol. 15, 425\u2013432 (1995).","journal-title":"Mol. Cell. Biol."},{"key":"BFnm0800_849_CR32","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/S0092-8674(00)81955-8","volume":"98","author":"T de Lange","year":"1999","unstructured":"de Lange, T. & Jacks, T. For better or worse? Telomerase inhibition and cancer. Cell 98, 273\u2013275 (1999).","journal-title":"Cell"},{"key":"BFnm0800_849_CR33","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1038\/13495","volume":"5","author":"WC Hahn","year":"1999","unstructured":"Hahn, W.C. et al. Inhibition of telomerase limits the growth of human cancer cells. Nature Med. 5, 1164\u20131170 (1999).","journal-title":"Nature Med."},{"key":"BFnm0800_849_CR34","doi-asserted-by":"publisher","first-page":"14276","DOI":"10.1073\/pnas.96.25.14276","volume":"96","author":"B-S Herbert","year":"1999","unstructured":"Herbert, B-S et al. Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death. Proc. Nat. Acad. Sci. USA 96, 14276\u201314281 (1999).","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"BFnm0800_849_CR35","doi-asserted-by":"publisher","first-page":"2932","DOI":"10.1128\/MCB.16.6.2932","volume":"16","author":"SE Holt","year":"1996","unstructured":"Holt, S.E., Wright, W.E. & Shay, J.W. Regulation of telomerase activity in immortal cell lines. Mol. Cell. Biol. 16, 2932\u20132939 (1996).","journal-title":"Mol. Cell. Biol."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm0800_849.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm0800_849","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/78592","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/nm0800_849.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T23:27:03Z","timestamp":1684452423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm0800_849"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,8]]},"references-count":35,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2000,8]]}},"alternative-id":["BFnm0800_849"],"URL":"https:\/\/doi.org\/10.1038\/78592","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,8]]}}}