Abstract
Mesotheliomas are malignant tumors of the pleural and peritoneal membranes which are often associated with asbestos exposure and with Simian virus 40 (SV40) infection. Telomerase activity is repressed in somatic cells and tissues but is activated in immortal and malignant cells. We evaluated telomerase activity in seven primary malignant mesothelioma biopsies and matched lung specimens and 20 mesothelioma cell lines and eight corresponding primary tumor cultures. All the tumor biopsies, and nearly all primary cell mesothelioma cultures and cell lines were telomerase positive. The findings in cell lines paralleled those observed in primary cultures in cases where paired samples were available. Next, we found that SV40, a DNA tumor virus present in ∼50% of mesothelioma biopsies in the USA, induced telomerase activity in primary human mesothelial cells, but not in primary fibroblasts. Telomerase activity became detectable as early as 72 h following wild-type (strain 776) SV40 infection, and a clear DNA ladder was detectable 1 week after infection. The amount of telomerase activity increased during passage in cell culture and appeared to parallel increases in the cellular amounts of the SV40 large T-antigen. Thus, SV40 infection leads to telomerase activity before the infected mesothelial cells become transformed and immortalized. SV40 infection of human fibroblasts did not cause detectable telomerase activity. We also determined that the SV40 small t-antigen (tag) plays an important role in inducing telomerase activity because this activity was undetectable or minimal in mesothelial cells infected and/or transformed by SV40 tag mutants. Asbestos alone did not induce telomerase activity, and asbestos did not influence telomerase activity in mesothelial cells infected with SV40. Induction of telomerase activity by SV40 may be related to the very high rate of mesothelial cell immortalization that is characteristically associated with SV40 infection of mesothelial cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Abbreviations
- SV40:
-
Simian virus 40
- Tag:
-
SV40 large tumor antigen
- tag:
-
SV40 small tumor antigen
- HM:
-
primary human mesothelial cells
- HF:
-
primary human fibroblasts
- MM:
-
malignant mesothelioma
- M.O.I.:
-
multiplicity of infection
- TRAP:
-
telomeric repeat amplification protocol
References
Ali SK, De Caprio JA . 2001 Sem. Cancer Biol. 11: 15–21
Bocchetta M, Di Resta I, Powers A, Fresco R, Tosolini A, Testa JR, Pass HI, Rizzo P, Carbone M . 2000 Proc. Natl. Acad. Sci. USA 97: 10214–10218
Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE . 1998 Science 279: 349–352
Broccoli D, Young JW, de Lange T . 1995 Proc. Natl. Acad. Sci. USA 92: 9082–9086
Broccoli D, Godley LA, Donehower LA, Varmus HE, de Lange T . 1996 Mol. Cell. Biol. 16: 3765–3772
Bryan TM, Reddel RR . 1994 Crit. Rev. Onco 5: 331–357
Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR . 1995 EMBO J. 14: 4240–4248
Cacciotti P, Libener R, Betta P, Martini F, Porta C, Procopio A, Strizzi L, Penengo L, Tognon M, Mutti L, Gaudino G . 2001 Proc. Natl. Acad. Sci. USA 98: 12032–12037
Carbone M, Pompetti F, Cicala C, Nguyen K, Dixon K, Dixon K . 1991 Molecular Basis of Human Cancer Nicolini C (ed) New York: Plenum Press pp 195–206
Carbone M, Rizzo P, Grimley PM, Procopio A, Mew DJ, Shridar V, de Bartolomeis A, Esposito V, Giuliano MT, Steinberg SM, Levine SM, Giordano A, Pass HI . 1997 Nat. Med. 3: 908–912
Carbone M, Kratzke RA, Testa JR . 2002 Semin. Oncol. in press
Chong L, van Steensel B, Broccoli D, Erdjument-Bromage H, Hanish J, Tempst P, de Lange T . 1995 Science 270: 1663–1667
Counter CM, Botelho FM, Wang P, Harley CB, Bacchetti S . 1994 J. Virol. 68: 3410–3414
De Luca A, Baldo A, Esposito V, Howard C, Bagella L, Rizzo P, Caputi M, Pass HI, Giordano GG, Baldi F, Carbone M, Giordano A . 1997 Nat. Med. 3: 913–916
Dunham MA, Neumann AA, Fasching CL, Reddel RR . 2000 Nat. Genet. 26: 447–450
Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA . 1999a Nature 400: 464–468
Hahn W, SA S, Brooks M, York S, Eaton E, Kurachi A, Beijersbergen R, Knoll J, Meyerson M, Weinberg R . 1999b Nat. Med. 5: 1164–1170
Jasani B, Cristaudo A, Emri SA, Gazdar AF, Gibbs A, Krynska B, Miller C, Mutti L, Radu C, Tognon M, Procopio A . 2001 Semin. Cancer Biol. 11: 49–61
Kang SS, Kwon T, Kwon DY, Do S . 1999 J. Biol. Chem. 274: 13085–13090
Ke Y, Reddel RR, Gerwin BI, Reddel HK, Somers ANA, McMenamin AM, LaVeck MA, Sthel RA, Lechnier JF, Harris CC . 1989 Am. J. Pathol. 134: 979–991
Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW . 1994 Science 266: 2011–2015
Klein B, Pastink A, Odijik H, Westerveld A, van der Eb AJ . 1990 Exp. Cell Res. 191: 256–262
Klein G . 2001 Proc. Natl. Acad. Sci. USA 97: 9830–9831
Klein G, Powers A, Croce CA . 2002 Oncogene 21: 1141–1149
Krynska B, Del Valle L, Croul S, Gordon J, Katsetos CD, Carbone M, Giordano A, Khalili K . 1999 Proc. Natl. Acad. Sci. USA 96: 11519–11524
Luderus ME, van Steensel B, Chong L, Sibon OC, Cremers FF, de Lange T . 1996 J. Cell. Biol. 135: 867–881
Ozer LH, Banga SS, Dasgupta T, Houghton JM, Hubbard K, Jha KH, Kim SH, Lenahan M, Pang Z, Pardinas JR, Ptsalis PC . 1996 Exp. Gerontol. 31: 303–310
Pipas JM, Levine AJ . 2001 Sem. Cancer Biol. 11: 23–30
Rizzo P, Di Resta I, Matker CM, Zhang A, Mutti L, Kast WM, Pass HI, Carbone M . 1998 Monaldi Arch. Chest Dis. 53: 202–210
Rundell K, Parakati R . 2001 Sem. Cancer Biol. 11: 5–13
Sager R . 1984 Cancer Cells 2: 487–493
Schrump DS, Waheed I . 2001 Sem. Cancer Biol. 11: 73–80
Shay JW, Wright WE . 1989 Exp. Cell Res. 184: 109–118
Shay JW, van der Haegen BA, Ying Y, Wright WE . 1993 Exp. Cell Res. 209: 45–52
Shay JW, Wright WE . 1996 Trends Genet. 12: 129–131
Shay JW, Zou Y, Hiyama E, Wright WE . 2001 Hum. Mol. Genet. 10: 677–685
Stewart SA, Weinberg RA . 2000 Semin. Cancer Biol. 10: 399–406
Testa SR, Carbone M, Hirvonen A, Khalili K, Krynska B, Linnainmaa K, Pooley FD, Rizzo P, Rusch V, Xiao GH . 1998 Cancer Res. 58: 4505–4509
Testa JR, Pass HI, Carbone M . 2001 Cancer: Principles and Practice of Oncology. DeVita Jr VT, Hellman S, Rosenberg SA. (eds) 6th edn Philadelphia: Lippincott Williams & Wilkins pp 1937–1943
Testa JR, Giordano A . 2001 Sem. Cancer Biol. 11: 31–38
van Steensel B, de Lange T . 1997 Nature 385: 740–743
Vaziri H, Benchimol S . 1998 Curr. Biol. 8: 279–282
Wright WE, Piatyszek MA, Rainey WE, Byrd W, Shay JW . 1996 Dev. Genet. 18: 173–179
Yeager TR, Neumann AA, Englezou A, Huschtscha LI, Noble JR, Reddel RR . 1999 Cancer Res. 59: 4175–4179
Yu J, Boyapati A, Rundell K . 2002 Virology 230: 132–138
Zhang X, Mar V, Zhou W, Harrington L, Robinson M . 1999 Genes Dev. 13: 2388–2399
Acknowledgements
We are grateful to Dr Kathleen Rundell for the critical reading of this manuscript. This work was supported by grants: ACS 8632 through a generous donation from Mr Dean Butchkovitz, by a grant from the Charlotte Geyer Foundation and by the Riviera Country Club, Illinois (to M Carbone); and by grants NCI CA-45745 and CA-06927, a gift from the Local #14 Mesothelioma Fund of the International Association of Heat and Frost Insulators & Asbestos Workers in memory of Hank Vaughan and Alice Haas, and an appropriation from the Commonwealth of Pennsylvania (to JR Testa).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Foddis, R., De Rienzo, A., Broccoli, D. et al. SV40 infection induces telomerase activity in human mesothelial cells. Oncogene 21, 1434–1442 (2002). https://doi.org/10.1038/sj.onc.1205203
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205203
Keywords
This article is cited by
-
Establishment and transcriptomic features of an immortalized hepatic cell line of the Chinese tree shrew
Applied Microbiology and Biotechnology (2020)
-
A prospect of cell immortalization combined with matrix microenvironmental optimization strategy for tissue engineering and regeneration
Cell & Bioscience (2019)
-
Establishment and characterization of an immortalized renal cell line of the Chinese tree shrew (Tupaia belangeri chinesis)
Applied Microbiology and Biotechnology (2019)
-
Lifetime extension of humpback whale skin fibroblasts and their response to lipopolysaccharide (LPS) and a mixture of polychlorinated biphenyls (Aroclor)
Cell Biology and Toxicology (2019)
-
Hairpin probe for sequence-specific recognition of double-stranded DNA on simian virus 40
Chemical Research in Chinese Universities (2018)