{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:30:25Z","timestamp":1773664225351,"version":"3.50.1"},"reference-count":40,"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\/78595","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T08:34:58Z","timestamp":1027672498000},"page":"852-855","source":"Crossref","is-referenced-by-count":98,"title":["Mice without telomerase: what can they teach us about human cancer?"],"prefix":"10.1038","volume":"6","author":[{"given":"Steven E.","family":"Artandi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald A.","family":"DePinho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","reference":[{"key":"BFnm0800_852_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 serial cultivation of human diploid cell strains. Exp. Cell Res. 25, 585\u2013621 (1961).","journal-title":"Exp. Cell Res."},{"key":"BFnm0800_852_CR2","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\u2013 352 (1998).","journal-title":"Science"},{"key":"BFnm0800_852_CR3","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\u2013 282 (1998).","journal-title":"Curr. Biol."},{"key":"BFnm0800_852_CR4","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. Comm. 179, 528\u2013534 (1991).","journal-title":"Biochem. Biophys. Res. Comm."},{"key":"BFnm0800_852_CR5","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_852_CR6","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1002\/j.1460-2075.1992.tb05245.x","volume":"11","author":"CM Counter","year":"1992","unstructured":"Counter, C.M. et al. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J. 11, 1921\u20131929 ( 1992).","journal-title":"EMBO J."},{"key":"BFnm0800_852_CR7","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_852_CR8","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_852_CR9","first-page":"182","volume":"8","author":"HJ Muller","year":"1938","unstructured":"Muller, H.J. The remaking of chromosomes. Collecting Net 8, 182\u2013195 (1938).","journal-title":"Collecting Net"},{"key":"BFnm0800_852_CR10","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1093\/genetics\/26.2.234","volume":"26","author":"B McClintock","year":"1941","unstructured":"McClintock, B. The stability of broken ends of chromosomes in Zea mays. Genetics 26, 234\u2013282 ( 1941).","journal-title":"Genetics"},{"key":"BFnm0800_852_CR11","first-page":"1496","volume":"201","author":"AM Olovnikov","year":"1971","unstructured":"Olovnikov, A.M. Principle of marginotomy in template synthesis of polynucleotides. Dokl. Akad. Nauk. SSSR 201, 1496\u20131499 (1971).","journal-title":"Dokl. Akad. Nauk. SSSR"},{"key":"BFnm0800_852_CR12","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/newbio239197a0","volume":"239","author":"JD Watson","year":"1972","unstructured":"Watson, J.D. Origin of concatemeric T7 DNA. Nat. New Biol. 239, 197\u2013201 (1972).","journal-title":"Nat. New Biol."},{"key":"BFnm0800_852_CR13","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_852_CR14","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0092-8674(00)81079-X","volume":"85","author":"M Serrano","year":"1996","unstructured":"Serrano, M. et al. Role of the INK4a locus in tumor suppression and cell mortality . Cell 85, 27\u201337 (1996).","journal-title":"Cell"},{"key":"BFnm0800_852_CR15","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/S0092-8674(00)80452-3","volume":"91","author":"T Kamijo","year":"1997","unstructured":"Kamijo, T. et al. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell 91, 649\u2013659 (1997).","journal-title":"Cell"},{"key":"BFnm0800_852_CR16","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1126\/science.283.5404.947","volume":"283","author":"T de Lange","year":"1999","unstructured":"de Lange, T. & DePinho, R.A. Unlimited mileage from telomerase? Science 283, 947\u2013949 (1999).","journal-title":"Science"},{"key":"BFnm0800_852_CR17","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_852_CR18","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\u2013 34 (1997).","journal-title":"Cell"},{"key":"BFnm0800_852_CR19","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/33345","volume":"392","author":"HW Lee","year":"1998","unstructured":"Lee, H.W. et al. Essential role of mouse telomerase in highly proliferative organs . Nature 392, 569\u2013574 (1998).","journal-title":"Nature"},{"key":"BFnm0800_852_CR20","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/580","volume":"19","author":"H Niida","year":"1998","unstructured":"Niida, H. et al. Severe growth defect in mouse cells lacking the telomerase RNA component. Nature Genet. 19, 203\u2013 206 (1998).","journal-title":"Nature Genet."},{"key":"BFnm0800_852_CR21","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/S0092-8674(00)80580-2","volume":"96","author":"KL Rudolph","year":"1999","unstructured":"Rudolph, K.L. et al. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96, 701\u2013712 (1999).","journal-title":"Cell"},{"key":"BFnm0800_852_CR22","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1126\/science.283.5406.1321","volume":"283","author":"J Karlseder","year":"1999","unstructured":"Karlseder, J., Broccoli, D., Dai, Y., Hardy, S. & de Lange, T. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 283, 1321\u2013 1325 (1999).","journal-title":"Science"},{"key":"BFnm0800_852_CR23","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_852_CR24","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1126\/science.275.5305.1478","volume":"275","author":"KE Kirk","year":"1997","unstructured":"Kirk, K.E., Harmon, B.P., Reichardt, I.K., Sedat, J.W. & Blackburn, E.H. Block in anaphase chromosome separation caused by a telomerase template mutation. Science 275, 1478\u20131481 (1997).","journal-title":"Science"},{"key":"BFnm0800_852_CR25","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1126\/science.282.5388.493","volume":"282","author":"TM Nakamura","year":"1998","unstructured":"Nakamura, T.M., Cooper, J.P. & Cech, T.R. Two modes of survival of fission yeast without telomerase . Science 282, 493\u2013496 (1998).","journal-title":"Science"},{"key":"BFnm0800_852_CR26","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/0092-8674(89)90132-3","volume":"57","author":"V Lundblad","year":"1989","unstructured":"Lundblad, V. & Szostak, J.W. A mutant with a defect in telomere elongation leads to senescence in yeast. Cell 57, 633\u2013643 (1989).","journal-title":"Cell"},{"key":"BFnm0800_852_CR27","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1038\/344126a0","volume":"344","author":"GL Yu","year":"1990","unstructured":"Yu, G.L., Bradley, J.D., Attardi, L.D. & Blackburn, E.H. In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs. Nature 344, 126\u2013132 (1990).","journal-title":"Nature"},{"key":"BFnm0800_852_CR28","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/0092-8674(93)90493-A","volume":"19","author":"LL Sandell","year":"1993","unstructured":"Sandell, L.L. & Zakian, V.A. Loss of a yeast telomere: arrest, recovery, and chromosome loss. Cell 19, 729\u2013739 (1993).","journal-title":"Cell"},{"key":"BFnm0800_852_CR29","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_852_CR30","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/22780","volume":"400","author":"WC Hahn","year":"1999","unstructured":"Hahn, W.C. et al. Creation of human tumour cells with defined genetic elements . Nature 400, 464\u2013468 (1999).","journal-title":"Nature"},{"key":"BFnm0800_852_CR31","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/0092-8674(93)90234-H","volume":"73","author":"V Lundblad","year":"1993","unstructured":"Lundblad, V. & Blackburn, E.H. An alternative pathway for yeast telomere maintenance rescues est1-senescence. Cell 73, 347\u2013360 (1993).","journal-title":"Cell"},{"key":"BFnm0800_852_CR32","doi-asserted-by":"publisher","first-page":"4240","DOI":"10.1002\/j.1460-2075.1995.tb00098.x","volume":"14","author":"TM Bryan","year":"1995","unstructured":"Bryan, T.M., Englezou, A., Gupta, J., Bacchetti, S. & Reddel, R.R. Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J. 14, 4240\u20134248 (1995).","journal-title":"EMBO J."},{"key":"BFnm0800_852_CR33","first-page":"2533","volume":"55","author":"C Chadeneau","year":"1995","unstructured":"Chadeneau, C., Hay, K., Hirte, H.W., Gallinger, S. & Bacchetti, S. Telomerase activity associated with acquisition of malignancy in human colorectal cancer. Cancer Res. 55, 2533\u20132536 (1995).","journal-title":"Cancer Res."},{"key":"BFnm0800_852_CR34","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/554","volume":"19","author":"KA Kolquist","year":"1998","unstructured":"Kolquist, K.A. et al. Expression of TERT in early premalignant lesions and a subset of cells in normal tissues. Nature Genet. 19, 182\u2013186 (1998).","journal-title":"Nature Genet."},{"key":"BFnm0800_852_CR35","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1038\/346866a0","volume":"346","author":"ND Hastie","year":"1990","unstructured":"Hastie, N.D. et al. Telomere reduction in human colorectal carcinoma and with ageing. Nature 346, 866\u2013 868 (1990).","journal-title":"Nature"},{"key":"BFnm0800_852_CR36","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1002\/(SICI)1098-2264(199708)19:4<267::AID-GCC9>3.0.CO;2-V","volume":"19","author":"T Nishizaki","year":"1997","unstructured":"Nishizaki, T. et al. Genetic alterations in primary breast cancers and their metastases: direct comparison using modified comparative genomic hybridization. Genes Chromosom. Cancer 19, 267\u2013272 (1997).","journal-title":"Genes Chromosom. Cancer"},{"key":"BFnm0800_852_CR37","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1002\/(SICI)1096-9896(199903)187:4<396::AID-PATH286>3.0.CO;2-L","volume":"187","author":"H Buerger","year":"1999","unstructured":"Buerger, H. et al. Comparative genomic hybridization of ductal carcinoma in situ of the breast-evidence of multiple genetic pathways. J. Pathol. 187, 396\u2013402 (1999).","journal-title":"J. Pathol."},{"key":"BFnm0800_852_CR38","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1002\/(SICI)1098-2264(199904)24:4<306::AID-GCC3>3.0.CO;2-5","volume":"24","author":"F Al-Mulla","year":"1999","unstructured":"Al-Mulla, F., Keith, W.N., Pickford, I.R., Going, J.J. & Birnie, G.D. Comparative genomic hybridization analysis of primary colorectal carcinomas and their synchronous metastases . Genes Chromosom. Cancer 24, 306\u2013 314 (1999).","journal-title":"Genes Chromosom. Cancer"},{"key":"BFnm0800_852_CR39","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\u2013 118 (1989).","journal-title":"Exp. Cell Res."},{"key":"BFnm0800_852_CR40","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 fibroblasts and mammary epithelial cells transfected with SV40 large T-antigen. Exp. Cell Res. 209, 45\u201352 (1993).","journal-title":"Exp. Cell Res."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm0800_852.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm0800_852","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/78595","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/nm0800_852.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_852"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,8]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2000,8]]}},"alternative-id":["BFnm0800_852"],"URL":"https:\/\/doi.org\/10.1038\/78595","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,8]]}}}