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Comparison of human mammary epithelial cells immortalized by simian virus 40 T-Antigen or by the telomerase catalytic subunit

Oncogene volume 21, pages 128–139 (2002)Cite this article

Abstract

We directly compared two methods of immortalizing human mammary epithelial cells (HMECs). Cells were transfected with an expression plasmid either for hTERT, the catalytic subunit of telomerase, or for the simian virus 40 (SV40) early region genes. Under standard culture conditions, HMECs were not immortalized by hTERT unless they had spontaneously ceased expression of the p16INK4a tumor suppressor gene. Untransfected HMECs had low levels of telomerase expression, and immortalization by both methods was associated with an increase in telomerase activity and prevention of telomere shortening. SV40-induced immortalization was accompanied by aberrant differentiation, loss of DNA damage response, karyotypic instability and, in some cases, tumorigenicity. hTERT-immortalized cells had fewer karyotypic changes, but had intact DNA damage responses, and features of normal differentiation. Although SV40-immortalized cells are useful for studies of carcinogenesis, hTERT-immortalized cells retain more properties of normal cells.

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References

  • Almasan A, Linke SP, Paulson TG, Huang L, Wahl GM . 1995 Cancer Metastasis Rev. 14: 59–73

  • Band V, De Caprio JA, Delmolina L, Kulesa V, Sager R . 1991 J. Virol. 65: 6671–6676

  • Band V, Zajchowski D, Kulesa V, Sager R . 1990 Proc. Natl. Acad. Sci. USA 87: 463–467

  • Bartek J, Bartkova J, Kyprianou N, Lanali E-N, Staskova Z, Shearer M, Chang S, Taylor-Papadimitriou J . 1991 Proc. Natl. Acad. Sci. USA 88: 3520–3524

  • Blackburn EH . 1991 Nature 350: 569–573

  • Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu C-P, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE . 1998 Science 279: 349–352

  • Brenner AJ, Stampfer MR, Aldaz CM . 1998 Oncogene 17: 199–205

  • Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR . 1995 EMBO J. 14: 4240–4248

  • Bryan TM, Reddel RR . 1994 Crit. Rev. Oncogenesis 5: 331–357

  • Cao Y-A, Gao Q, Water DE, Band V . 1997 Cancer Res. 57: 5584–5589

  • Colgin LM, Reddel RR . 1999 Curr. Opin. Genet. Dev. 9: 97–103

  • Colgin LM, Wilkinson C, Englezou A, Kilian A, Robinson MO, Reddel RR . 2000 Neoplasia 2: 426–432

  • Counter CM, Avilion AA, LeFeuvre CE, Stewart NG, Greider CW, Harley CB, Bacchetti S . 1992 EMBO J. 11: 1921–1929

  • Dickson MA, Hahn WC, Ino Y, Ronfard V, Wu JY, Weinberg RA, Louis DN, Li FP, Rheinwald JG . 2000 Mol. Cell. Biol. 20: 1436–1447

  • Elenbaas B, Spirio L, Koerner F, Fleming MD, Zimonjic DB, Donaher JL, Popescu NC, Hahn WC, Weinberg RA . 2001 Genes Dev. 15: 50–65

  • Farwell DG, Shera KA, Koop JI, Bonnet GA, Matthews CP, Reuther GW, Coltrera MD, McDougall JK, Klingelhutz AJ . 2000 Am. J. Pathol. 156: 1537–1547

  • Foster SA, Galloway DS . 1996 Oncogene 12: 1773–1779

  • Foster SA, Wong DJ, Barrett MT, Galloway DA . 1998 Mol. Cell. Biol. 18: 1793–1801

  • Gao Q, Hauser SH, Liu X-L, Wazer DE, Madoc-Jones H, Band V . 1996 Cancer Res. 56: 3129–3133

  • Garbe J, Wong M, Wigington D, Yaswen P, Stampfer MR . 1999 Oncogene 18: 2169–2180

  • Gollahon LS, Shay JW . 1996 Oncogene 12: 715–725

  • Greider CW, Blackburn EH . 1985 Cell 43: 405–413

  • Harley CB . 1991 Mutat. Res. 256: 271–282

  • Hayflick L, Moorhead PS . 1961 Exp. Cell Res. 25: 585–621

  • Hooijberg E, Ruizendaal JJ, Snijders PJF, Kueter EWM, Walboomers JMM, Spits H . 2000 J. Immunol. 165: 4239–4245

  • Huschtscha LI, Neumann AA, Noble JR, Reddel RR . 2001 Exp. Cell Res. 265: 125–134

  • Huschtscha LI, Noble JR, Neumann AA, Moy EL, Barry P, Melki JR, Clark SJ, Reddel RR . 1998 Cancer Res. 58: 3508–3512

  • Jiang X-R, Jimenez G, Chang E, Frolkis M, Kusler B, Sage M, Beeche M, Bodnar AG, Wahl GM, Tlsty TD, Chiu C-P . 1999 Nat. Genet. 21: 111–114

  • Kao C-Y, Nomata K, Oakley CS, Welsch CW, Chang C-C . 1995 Carcinogenesis 16: 531–538

  • Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PLC, Coviello GM, Wright WE, Weinrich SL, Shay JW . 1994 Science 266: 2011–2015

  • Kiyono T, Foster SA, Koop JI, McDougall JK, Galloway DA, Klingelhutz AJ . 1998 Nature 396: 84–88

  • Lebeau J, Gerbault-Seureau M, Lemieux N, Apiou F, Calvo F, Berthon P, Goubin G, Dutrillaux B . 1995 Int. J. Cancer 60: 244–248

  • MacKenzie KL, Franco S, May C, Sadelain M, Moore MAS . 2000 Exp. Cell Res. 259: 336–350

  • Migliaccio M, Amacker M, Just T, Reichenbach P, Valmori D, Cerottini J-C, Romero P, Nabholz M . 2000 J. Immunol. 165: 4978–4984

  • Mitelman F (ed) . 1995 ISCN: An International System for Human Cytogenic Nomenclature S. Karger: Basel

    Google Scholar 

  • Morales CP, Holt SE, Ouellette M, Kaur KJ, Yan Y, Wilson KS, White MA, Wright WE, Shay JW . 1999 Nat. Genet. 21: 115–118

  • Nonet GH, Stampfer MR, Chin K, Gray JW, Collins CC, Yaswen P . 2001 Cancer Res. 61: 1250–1254

  • Nugent CI, Lundblad V . 1998 Genes Dev. 12: 1073–1085

  • Olovnikov AM . 1973 J. Theor. Biol. 41: 181–190

  • Perrem K, Bryan TM, Englezou A, Hackl T, Moy EL, Reddel RR . 1999 Oncogene 18: 3383–3390

  • Peterson WD, Simpson WF, Hukku B . 1979 Methods Enzymol. 58: 164–178

  • Ramirez RD, Morales CP, Herbert B-S, Rohde JM, Passons C, Shay JW, Wright WE . 2001 Genes Dev. 15: 398–403

  • Romanov SR, Kozakiewicz BK, Holst CR, Stampfer MR, Haupt LM, Tlsty D . 2001 Nature 409: 633–637

  • Sack Jr GH . 1981 In Vivo 17: 1–19

  • Sakamoto K, Howard T, Ogryzko V, Xu N-Z, Corsico CC, Jones D, Howard B . 1993 Oncogene 8: 1887–1893

  • Smyth CM, Helmer MA, Dalla Pozza L, Rowe PB . 1993 Pathology 25: 388–393

  • Sprung CN, Sabatier L, Murnane JP . 1999 Exp. Cell Res. 247: 29–37

  • Stampfer MR . 1985 J. Tissue Cult. Methods 9: 107–115

  • Stampfer MR, Bartley JC . 1985 Proc. Natl. Acad. Sci. USA 82: 2394–2398

  • Stampfer MR, Garbe J, Levine G, Lichtsteiner S, Vasserot AP, Yaswen P . 2001 Proc. Natl. Acad. Sci. USA 98: 4498–4503

  • Sun W, Kang K-S, Morita I, Trosko JE, Chang C-C . 1999 Cancer Res. 59: 6118–6123

  • Taylor-Papadimitriou J, Stampfer M, Bartek J, Lewis A, Boshell M, Lane EB, Leigh IM . 1989 J. Cell Sci. 94: 403–413

  • van Steensel B, de Lange T . 1997 Nature 385: 740–743

  • Vaziri H, Squire JA, Pandita TK, Bradley G, Kuba RM, Zhang H, Gulyas S, Hill RP, Nolan GP, Benchimol S . 1999 Mol. Cell. Biol. 19: 2373–2379

  • Wazer DE, Chu Q, Liu X-L, Gao Q, Safaii H, Band V . 1994 Mol. Cell. Biol. 14: 2468–2478

  • Weinrich SL, Pruzan R, Ma L, Ouellette M, Tesmer VM, Holt SE, Bodnar AG, Lichtsteiner S, Kim NW, Trager JB, Taylor RD, Carlos R, Andrews WH, Wright WE, Shay JW, Harley CB, Morin GB . 1997 Nat. Genet. 17: 498–502

  • Yang J, Chang E, Cherry AM, Bangs CD, Oei Y, Bodnar A, Bronstein A, Chiu C-P, Herron GS . 1999 J. Biol. Chem. 274: 26141–26148

  • Yeager TR, Neumann AA, Englezou A, Huschtscha LI, Noble JR, Reddel RR . 1999 Cancer Res. 59: 4175–4179

  • Yilmaz A, Gaide A-C, Sordat B, Borbenyi Z, Lahm H, Imam A, Schreyer M, Odartchenko N . 1993 Br. J. Cancer 68: 868–873

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Acknowledgements

The research was supported by the National Breast Cancer Foundation, the National Health and Medical Research Council of Australia, the Carcinogenesis Fellowship of the New South Wales Cancer Council, and a Yass Memorial scholarship. The authors thank Christine Smyth for FACscan analysis, and CMRI Bioservices for nude mouse studies.

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Authors and Affiliations

  1. Children's Medical Research Institute, 214 Hawkesbury Road, 2145, Westmead, Australia

    Christian D Toouli, Lily I Huschtscha, Axel A Neumann, Jane R Noble, Lorel M Colgin & Roger R Reddel

  2. Children's Hospital of Michigan, Cell Culture Laboratory, 3901 Beaubien Boulevard, Detroit, 48201, Michigan, USA

    Bharati Hukku

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  1. Christian D Toouli
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Correspondence to Roger R Reddel.

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Toouli, C., Huschtscha, L., Neumann, A. et al. Comparison of human mammary epithelial cells immortalized by simian virus 40 T-Antigen or by the telomerase catalytic subunit. Oncogene 21, 128–139 (2002). https://doi.org/10.1038/sj.onc.1205014

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