Abstract
Group C adenovirus is latent in human tissues and can malignantly transform cells. The purpose of this study was to investigate the association between this virus and lung cancer. We investigated latent adenoviral infection using the nested polymerase chain reaction and in situ hybridization in transbronchial biopsy specimens from patients with small-cell lung cancer and non-small-cell lung cancer. The polymerase chain reaction was performed on DNA extracts with two sets of primers directed at a 261-base-pair target sequence of the E1A region of the adenoviral genome. In situ hybridization was performed on histological sections using DNA representing the entire adenovirus type 5 genome. E1A target DNA was present in 11 (31%) of 35 cases of small-cell lung cancer but in none of the 40 cases of non-small-cell lung cancer (P<0.01). Of the 11 cases found positive by PCR, 8 were positive for adenovirus DNA by in situ hybridization. Adenovirus was prominent in tumor cells in 5 of the 8 cases, and in normal epithelial cells in the 3 remaining cases. Adenovirus DNA was not detected by in situ hybridization in specimens in which E1A DNA was not detected by the polymerase chain reaction. Small-cell lung cancer has mutations or deletions in the p53 and retinoblastoma genes more frequently than are found in non-small-cell lung cancer. Therefore, we speculate that adenovirus infection might participate in the pathogenesis of SCLC by producing mutation in these genes, rather than by inhibiting the function of these proteins.
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Abbreviations
- PCR :
-
polymerase chain reaction
- ISH :
-
in situ hybridization
- RB :
-
retinoblastoma
References
Carter D, Eggleston JC (1983) Tumors of the lower respiratory tract. Armed Forces Institute of Pathology, Washington, DC
Challappan SP, Hiebert S, Mudryj M, Horowitz JM, Nevins JR (1991) The E2F transcription factor is a cellular target for the RB protein. Cell 65:1053–1061
Goelz SE, Hamilton SR, Vogelstein B (1985) Purification of DNA from formaldehyde fixed and paraffin embedded human tissue. Biochem Biophys Res Commun 130:118–126
Graham FL (1984) Transformation by and oncogenicity of human adenoviruses. In: Ginsberg HS (ed) The adenoviruses. Plenum, New York, pp 339–398
Graham FL, Smiley J, Russel WC, Nairn R (1977) Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol 36:59–72
Green M, Wold WSM, Mackey JK, Rigden P (1979) Analysis of human tonsil and cancer DNAs and RNAs for DNA sequences of group C (serotypes 1,2,5, and 6) human adenoviruses. Proc Natl Acad Sci USA 76:6606–6610
Horbath J, Palkonyay L, Weber J (1986) Group C adenovirus DNA sequences in human lymphoid cells. J Virol 59:189–192
Kwok S, Sninsky JJ (1989) Application of PCR to the detection of human infectious diseases. In: Erlich HA (ed) PCR technology. Principles and applications for DNA amplification. Stockton, New York, pp 235–244
Li H, Gyllensten UB, Cui X, Saiki R, Erlich HA, Arnheim N (1988) Amplification and analysis of DNA sequences in single human sperm and diploid cells. Nature 335:414–417
Matsuse T, Hayashi S, Kuwano K, Keunecke H, Jeffries WA, Hogg JC (1992) Latent adenoviral infection in the pathogenesis of chronic airways obstruction. Am Rev Respir Dis 146:177–184
Morgenbesser SD, Williams BO, Jacks T, DePinho RA (1994) p53 dependent apoptosis produced by Rb-deficiency in the developing mouse lens. Nature 371:72–74
Nevin JR (1992) E2F: A link between the Rb tumor suppressor protein and viral oncoproteins. Science 258:424–428
Pan H, Griep AE (1994) Altered cell cycle regulation in the lens of HPV-16 E6 or E7 transgenic mice: Implications for tumor suppressor gene function in development. Genes Dev 8:1285–1299
Rao L, Debbas M, Sabbatini P, Hockenbery D, Korsmeyer S, White E (1992) Adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc Natl Acad Sci USA 89:7742–7746
Renee Yew P, Liu X, Berk AJ (1993) Adenovirus E1B oncoprotein tethers a transcriptional repression domain to p53. Genes Dev 8:190–202
Scharf SJ, Horn GT, Erlich HA (1986) Direct cloning and sequence analysis of emzymatically amplified genomic sequences. Science 233:1076–1078
Shimizu E, Coxon A, Otterson GA, Steinberg SM, Kratzke RA, Kim YW, Fedorko J, Oie H, Johnson BE, Mulshine JL, Minna JD, Gazdar AF, Kaye FJ (1994) RB protein status and clinical correlation from 171 cell lines representing lung cancer, extrapulmonary small cell carcinoma, and mesothelioma. Oncogene 9:2441–2448
Shin RW, Iwaki T, Kitamoto T, Tateishi J (1991) Methods in laboratory investigation. Hydrated autoclave pretreatment enhances TAU. Immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues. Lab Invest 64:693–702
Vogelstein B, Kinzler KW (1992) p53 function and dysfunction. Cell 70:523–526
Weintraub SJ, Prater CA, Dean DC (1992) Retinoblastoma protein switches the E2F site from a positive to negative element. Nature 358:259–261
White E (1993) Regulation of apoptosis by the transforming genes of the DNA tumor virus adenovirus. Exp Biol Med 204:30–39
White E (1994) p53, guardian of rb. Nature 371:21–22
White E, Sabbatini P, Debbas M, Wold WSM, Kusher DI, Gooding LR (1992) The 19-kilodalton adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor α. Mol Cell Biol 12:2570–2580
Whyte P, Buchkovich KJ, Holowitz JM, Friend SH, Rayback M, Weinberg RA, Harlow E (1988) Association between an oncogene and antioncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature 334:124–129
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Kuwano, K., Kawasaki, M., Kunitake, R. et al. Detection of group C adenovirus DNA in small-cell lung cancer with the nested polymerase chain reaction. J Cancer Res Clin Oncol 123, 377–382 (1997). https://doi.org/10.1007/BF01240120
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DOI: https://doi.org/10.1007/BF01240120