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[Cancer Research 48, 1904-1909, April 1, 1988]
© 1988 American Association for Cancer Research
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Transformation of Human Bronchial Epithelial Cells by Infection with SV40 or Adenovirus-12 SV40 Hybrid Virus, or Transfection via Strontium Phosphate Coprecipitation with a Plasmid Containing SV40 Early Region Genes

Roger R. Reddel1, Yang Ke2, Brenda I. Gerwin, Mary G. McMenamin, John F. Lechner, Robert T. Su3, Douglas E. Brash, Joo-Bae Park4, Johng S. Rhim and Curtis C. Harris5

Laboratory of Human Carcinogenesis [R. R. R., Y. K., B. I. C., M. G. M., J. F. L., R. T. S., D. E. B., C. C. H.], and Laboratory of Cellular and Molecular Biology [J-B. P., J. S. R.], Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20892

Normal human bronchial epithelial cells were infected with SV40 virus or an adenovirus 12-SV40 hybrid virus, or transfected via strontium phosphate coprecipitation with plasmids containing the SV40 early region genes. Colonies of morphologically altered cells were isolated and cultured; these cells had extended culture lifespans compared to normal human bronchial epithelial cells. All cultures eventually underwent senescence, with the exception of one which appears to have unlimited proliferative potential. Colonies arising after viral infection were screened for virus production by cocultivation with Vero cells; only viral nonproducer cultures were analyzed further. The cells retained electron microscopic features of epithelial cells, and keratin and SV40 T-antigen were detected by indirect immunofluorescence. All of the cultures were aneuploid with karyotypic abnormalities characteristic of SV40-transformed cells. No tumors formed after s.c. injection of the cells in nude mice. These cells should be useful for studies of multistage bronchial epithelial carcinogenesis.

1 Supported by a C. J. Martin Fellowship of National Health and Medical Research Council of Australia.

2 Supported by an NIH Visiting Fellowship.

3 Present address: Department of Microbiology, University of Kansas, Lawrence, KS 66045.

4 Present address: Department of Biochemistry, College of Medicine, Seoul National University, Seoul, Korea.

5 To whom requests for reprints should be addressed.

Received 6/23/87. Revised 12/15/87. Accepted 12/28/87.




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H. Yuan, T. Veldman, K. Rundell, and R. Schlegel
Simian Virus 40 Small Tumor Antigen Activates AKT and Telomerase and Induces Anchorage-Independent Growth of Human Epithelial Cells
J. Virol., October 2, 2002; 76(21): 10685 - 10691.
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 Am. J. Respir. Cell Mol. Bio.Home page
S. Oudin and J. Pugin
Role of MAP Kinase Activation in Interleukin-8 Production by Human BEAS-2B Bronchial Epithelial Cells Submitted to Cyclic Stretch
Am. J. Respir. Cell Mol. Biol., July 1, 2002; 27(1): 107 - 114.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
T. Hida, K.-i. Kozaki, H. Ito, O. Miyaishi, Y. Tatematsu, T. Suzuki, K. Matsuo, T. Sugiura, M. Ogawa, T. Takahashi, et al.
Significant Growth Inhibition of Human Lung Cancer Cells Both in Vitro and in Vivo by the Combined Use of a Selective Cyclooxygenase 2 Inhibitor, JTE-522, and Conventional Anticancer Agents
Clin. Cancer Res., July 1, 2002; 8(7): 2443 - 2447.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
K. Miura, E. D. Bowman, R. Simon, A. C. Peng, A. I. Robles, R. T. Jones, T. Katagiri, P. He, H. Mizukami, L. Charboneau, et al.
Laser Capture Microdissection and Microarray Expression Analysis of Lung Adenocarcinoma Reveals Tobacco Smoking- and Prognosis-related Molecular Profiles
Cancer Res., June 1, 2002; 62(11): 3244 - 3250.
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 J. Biol. Chem.Home page
A. Graness, C. E. Chwieralski, D. Reinhold, L. Thim, and W. Hoffmann
Protein Kinase C and ERK Activation Are Required for TFF- peptide-stimulated Bronchial Epithelial Cell Migration and Tumor Necrosis Factor-alpha -induced Interleukin-6 (IL-6) and IL-8 Secretion
J. Biol. Chem., May 17, 2002; 277(21): 18440 - 18446.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
W.-H. Chang, S. P.-M. Reddy, Y.-P. P. Di, K. Yoneda, R. Harper, and R. Wu
Regulation of Thioredoxin Gene Expression by Vitamin A in Human Airway Epithelial Cells
Am. J. Respir. Cell Mol. Biol., May 1, 2002; 26(5): 627 - 635.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
N. Asokananthan, P. T. Graham, J. Fink, D. A. Knight, A. J. Bakker, A. S. McWilliam, P. J. Thompson, and G. A. Stewart
Activation of Protease-Activated Receptor (PAR)-1, PAR-2, and PAR-4 Stimulates IL-6, IL-8, and Prostaglandin E2 Release from Human Respiratory Epithelial Cells
J. Immunol., April 1, 2002; 168(7): 3577 - 3585.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
C. B. Matranga and G. I. Shapiro
Selective Sensitization of Transformed Cells to Flavopiridol-induced Apoptosis following Recruitment to S-Phase
Cancer Res., March 1, 2002; 62(6): 1707 - 1717.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
K. Takami, N. Takuwa, H. Okazaki, M. Kobayashi, T. Ohtoshi, S. Kawasaki, M. Dohi, K. Yamamoto, T. Nakamura, M. Tanaka, et al.
Interferon-gamma Inhibits Hepatocyte Growth Factor-Stimulated Cell Proliferation of Human Bronchial Epithelial Cells . Upregulation of p27kip1 Cyclin-Dependent Kinase Inhibitor
Am. J. Respir. Cell Mol. Biol., February 1, 2002; 26(2): 231 - 238.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
T. R. Van Vleet, K. Mace, and R. A. Coulombe Jr.
Comparative Aflatoxin B1 Activation and Cytotoxicity in Human Bronchial Cells Expressing Cytochromes P450 1A2 and 3A4
Cancer Res., January 1, 2002; 62(1): 105 - 112.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
H. Konishi, T. Nakagawa, T. Harano, K. Mizuno, H. Saito, A. Masuda, H. Matsuda, H. Osada, and T. Takahashi
Identification of Frequent G2 Checkpoint Impairment and a Homozygous Deletion of 14-3-3{epsilon} at 17p13.3 in Small Cell Lung Cancers
Cancer Res., January 1, 2002; 62(1): 271 - 276.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
F. Lonardo, K. H. Dragnev, S. J. Freemantle, Y. Ma, N. Memoli, D. Sekula, E. A. Knauth, J. S. Beebe, and E. Dmitrovsky
Evidence for the Epidermal Growth Factor Receptor As a Target for Lung Cancer Prevention
Clin. Cancer Res., January 1, 2002; 8(1): 54 - 60.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
G. Feng, X.-c. Xu, E. M. Youssef, and R. Lotan
Diminished Expression of S100A2, a Putative Tumor Suppressor, at Early Stage of Human Lung Carcinogenesis
Cancer Res., November 1, 2001; 61(21): 7999 - 8004.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. O. Aksoy, W. Bin, Y. Yang, D. Yun-You, and S. G. Kelsen
Nuclear factor-kappa B augments beta 2-adrenergic receptor expression in human airway epithelial cells
Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1271 - L1278.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
M. Oertel, A. Graness, L. Thim, F. Buhling, H. Kalbacher, and W. Hoffmann
Trefoil Factor Family-Peptides Promote Migration of Human Bronchial Epithelial Cells . Synergistic Effect with Epidermal Growth Factor
Am. J. Respir. Cell Mol. Biol., October 1, 2001; 25(4): 418 - 424.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
F. F. Little, W. W. Cruikshank, and D. M. Center
IL-9 Stimulates Release of Chemotactic Factors from Human Bronchial Epithelial Cells
Am. J. Respir. Cell Mol. Biol., September 1, 2001; 25(3): 347 - 352.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
S. P. Hussain, P. Amstad, K. Raja, M. Sawyer, L. Hofseth, P. G. Shields, A. Hewer, D. H. Phillips, D. Ryberg, A. Haugen, et al.
Mutability of p53 Hotspot Codons to Benzo(a)pyrene Diol Epoxide (BPDE) and the Frequency of p53 Mutations in Nontumorous Human Lung
Cancer Res., September 1, 2001; 61(17): 6350 - 6355.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
J. M. Kurie and R. N. Dubois
Prostaglandin E Synthase: Another Enzyme in the Cyclooxygenase Pathway Driving Epithelial Cancer?
Clin. Cancer Res., September 1, 2001; 7(9): 2608 - 2610.
[Full Text] [PDF]

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 CarcinogenesisHome page
A. Arora, C. A. Willhite, and D. C. Liebler
Interactions of {beta}-carotene and cigarette smoke in human bronchial epithelial cells
Carcinogenesis, August 1, 2001; 22(8): 1173 - 1178.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
W. Wu, J. M. Samet, A. J. Ghio, and R. B. Devlin
Activation of the EGF receptor signaling pathway in airway epithelial cells exposed to Utah Valley PM
Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L483 - L489.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
J. Cuppoletti, K. P. Tewari, A. M. Sherry, E. Y. Kupert, and D. H. Malinowska
ClC-2 Cl{-} channels in human lung epithelia: activation by arachidonic acid, amidation, and acid-activated omeprazole
Am J Physiol Cell Physiol, July 1, 2001; 281(1): C46 - C54.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
K. Uetani, M. E. Arroliga, and S. C. Erzurum
Double-Stranded RNA Dependence of Nitric Oxide Synthase 2 Expression in Human Bronchial Epithelial Cell Lines BET-1A and BEAS-2B
Am. J. Respir. Cell Mol. Biol., June 1, 2001; 24(6): 720 - 726.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
S. Matsukura, C. Stellato, S. N. Georas, V. Casolaro, J. R. Plitt, K. Miura, S. Kurosawa, U. Schindler, and R. P. Schleimer
Interleukin-13 Upregulates Eotaxin Expression in Airway Epithelial Cells by a STAT6-Dependent Mechanism
Am. J. Respir. Cell Mol. Biol., June 1, 2001; 24(6): 755 - 761.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
K. Uetani, M. J. Thomassen, and S. C. Erzurum
Nitric oxide synthase 2 through an autocrine loop via respiratory epithelial cell-derived mediator
Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1179 - L1188.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
O. Sakamoto, M. Suga, T. Suda, and M. Ando
Expression of discoidin domain receptor 1 tyrosine kinase on the human bronchial epithelium
Eur. Respir. J., May 1, 2001; 17(5): 969 - 974.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
S. Kawasaki, H. Takizawa, K. Takami, M. Desaki, H. Okazaki, T. Kasama, K. Kobayashi, K. Yamamoto, K. Nakahara, M. Tanaka, et al.
Benzene-Extracted Components Are Important for the Major Activity of Diesel Exhaust Particles . Effect on Interleukin-8 Gene Expression in Human Bronchial Epithelial Cells
Am. J. Respir. Cell Mol. Biol., April 1, 2001; 24(4): 419 - 426.
[Abstract] [Full Text]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
W. Bin, M. O. Aksoy, Y. Yang, and S. G. Kelsen
IL-1{beta} enhances {beta}2-adrenergic receptor expression in human airway epithelial cells by activating PKC
Am J Physiol Lung Cell Mol Physiol, April 1, 2001; 280(4): L675 - L679.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
C. Stellato, M. E. Brummet, J. R. Plitt, S. Shahabuddin, F. M. Baroody, M. C. Liu, P. D. Ponath, and L. A. Beck
Cutting Edge: Expression of the C-C Chemokine Receptor CCR3 in Human Airway Epithelial Cells
J. Immunol., February 1, 2001; 166(3): 1457 - 1461.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
W. Reed, J. L. Carson, B. M. Moats-Staats, T. Lucier, P.-c. Hu, L. Brighton, T. M. Gambling, C.-H. Huang, M. W. Leigh, and A. M. Collier
Characterization of an Axonemal Dynein Heavy Chain Expressed Early in Airway Epithelial Ciliogenesis
Am. J. Respir. Cell Mol. Biol., December 1, 2000; 23(6): 734 - 741.
[Abstract] [Full Text]

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 The OncologistHome page
K. H. Dragnev, J. R. Rigas, and E. Dmitrovsky
The Retinoids and Cancer Prevention Mechanisms
Oncologist, October 1, 2000; 5(5): 361 - 368.
[Abstract] [Full Text]

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 J. Immunol.Home page
J. Kim, S. P. Sanders, E. S. Siekierski, V. Casolaro, and D. Proud
Role of NF-{kappa}B in Cytokine Production Induced from Human Airway Epithelial Cells by Rhinovirus Infection
J. Immunol., September 15, 2000; 165(6): 3384 - 3392.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
A. Venkatakrishnan, A. A. Stecenko, G. King, T. R. Blackwell, K. L. Brigham, J. W. Christman, and T. S. Blackwell
Exaggerated Activation of Nuclear Factor-kappa B and Altered Ikappa B-beta Processing in Cystic Fibrosis Bronchial Epithelial Cells
Am. J. Respir. Cell Mol. Biol., September 1, 2000; 23(3): 396 - 403.
[Abstract] [Full Text]

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 Ann. Thorac. Surg.Home page
R. A. Vertrees, J. B. Zwischenberger, P. J. Boor, and S. D. Pencil
Oncogenic ras results in increased cell kill due to defective thermoprotection in lung cancer cells
Ann. Thorac. Surg., June 1, 2000; 69(6): 1675 - 1680.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
F. H. Guo, S. A. A. Comhair, S. Zheng, R. A. Dweik, N. T. Eissa, M. J. Thomassen, W. Calhoun, and S. C. Erzurum
Molecular Mechanisms of Increased Nitric Oxide (NO) in Asthma: Evidence for Transcriptional and Post-Translational Regulation of NO Synthesis
J. Immunol., June 1, 2000; 164(11): 5970 - 5980.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
T. Hida, K.-i. Kozaki, H. Muramatsu, A. Masuda, S. Shimizu, T. Mitsudomi, T. Sugiura, M. Ogawa, and T. Takahashi
Cyclooxygenase-2 Inhibitor Induces Apoptosis and Enhances Cytotoxicity of Various Anticancer Agents in Non-Small Cell Lung Cancer Cell Lines
Clin. Cancer Res., May 1, 2000; 6(5): 2006 - 2011.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
A. G. Frick, T. D. Joseph, L. Pang, A. M. Rabe, J. W. St. Geme III, and D. C. Look
Haemophilus influenzae Stimulates ICAM-1 Expression on Respiratory Epithelial Cells
J. Immunol., April 15, 2000; 164(8): 4185 - 4196.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
M. M.-J. Chang, R. Harper, D. M. Hyde, and R. Wu
A Novel Mechanism of Retinoic Acid-Enhanced Interleukin-8 Gene Expression in Airway Epithelium
Am. J. Respir. Cell Mol. Biol., April 1, 2000; 22(4): 502 - 510.
[Abstract] [Full Text]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Oortgiesen, B. Veronesi, G. Eichenbaum, P. F. Kiser, and S. A. Simon
Residual oil fly ash and charged polymers activate epithelial cells and nociceptive sensory neurons
Am J Physiol Lung Cell Mol Physiol, April 1, 2000; 278(4): L683 - L695.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
A.-C. Souici, J. Mirkovitch, P. Hausel, L. K.Keefer, and E. Felley-Bosco
Transition mutation in codon 248 of the p53 tumor suppressor gene induced by reactive oxygen species and a nitric oxide-releasing compound
Carcinogenesis, February 1, 2000; 21(2): 281 - 287.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
S. Abe, H. Nakamura, S. Inoue, H. Takeda, H. Saito, S. Kato, N. Mukaida, K. Matsushima, and H. Tomoike
Interleukin-8 Gene Repression by Clarithromycin Is Mediated by the Activator Protein-1 Binding Site in Human Bronchial Epithelial Cells
Am. J. Respir. Cell Mol. Biol., January 1, 2000; 22(1): 51 - 60.
[Abstract] [Full Text]

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 J. Immunol.Home page
S. Matsukura, C. Stellato, J. R. Plitt, C. Bickel, K. Miura, S. N. Georas, V. Casolaro, and R. P. Schleimer
Activation of Eotaxin Gene Transcription by NF-{kappa}B and STAT6 in Human Airway Epithelial Cells
J. Immunol., December 15, 1999; 163(12): 6876 - 6883.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
M. Arima, J. Plitt, C. Stellato, C. Bickel, S. Motojima, S. Makino, T. Fukuda, and R. P. Schleimer
Expression of Interleukin-16 by Human Epithelial Cells . Inhibition by Dexamethasone
Am. J. Respir. Cell Mol. Biol., December 1, 1999; 21(6): 684 - 692.
[Abstract] [Full Text]

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 Am. J. Respir. Cell Mol. Bio.Home page
A. M. Fernandes, A. W. Hamburger, and B. I. Gerwin
Dominance of ErbB-1 Heterodimers in Lung Epithelial Cells Overexpressing ErbB-2 . Both ErbB-1 and ErbB-2 Contribute Significantly to Tumorigenicity
Am. J. Respir. Cell Mol. Biol., December 1, 1999; 21(6): 701 - 709.
[Abstract] [Full Text]


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