Abstract
Tumour necrosis factor (TNF) was found originally in mouse serum after intravenous injection of bacterial endotoxin into mice primed with viable Mycobacterium bovis, strain Bacillus Calmette-Guerin (BCG)1. TNF-containing serum from mice is cytotoxic or cytostatic to a number of mouse and human transformed cell lines, but less or not toxic to normal cells in vitro. It causes necrosis of transplantable tumours in mice. TNF also occurs in serum of rat1, rabbit1,2 and guinea pig3. Rabbit TNF has been purified recently to give a single band on SDS-polyacrylamide gel electrophoresis (PAGE). The purified TNF had a relative molecular mass (Mr) 40,000±5,000 measured by gel filtration, and 17,000 by SDS-PAGE. Its isoelectric point is 5.0±0.3 (ref. 4). The necrotic activity in vivo and the cytotoxicity in vitro are produced by the same substance5. The gene encoding TNF has been identified in a human genomic DNA library using as a probe a cloned cDNA encoding a portion of rabbit TNF. The regions of this gene encoding an amino-acid sequence corresponding to mature TNF have been expressed in Escherichia coli and the product of this expression isolated in pure form and shown to produce necrosis of murine tumours in vivo.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 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
Change history
01 April 1985
Nature 313, 803-806 (1985) On page 805, Figures 2 and 3 were transposed.
References
Carswell, E. A. et al. Proc. natn. Acad. Sci. U.S.A. 72, 3666–3670 (1975).
Matthews, N. & Watkins, J.F. Br. J. Cancer 38, 302–309 (1978).
Zacharchuk, C. M., Drysdale, B-E., Mayer, M. M. & Shin, H. S. Proc. natn. Acad. Sci. U.S.A. 80, 6341–6345 (1983).
Hayashi, H., Kiyota, T., Sohmura, Y. & Haranaka, K. Proc. 43rd Japan. Cancer Assoc. No. 1132, 314 (1984).
Hori, K., Hayashi, H., Sohmura, Y. & Haranaka, K. Proc. 43rd Japan. Cancer Assoc. No. 1130, 314 (1984).
Matthews, N. Immunology 44, 135–142 (1981).
Matthews, N. Immunology 48, 321–327 (1983).
Williamson, B. D., Carswell, E. A., Rubin, B. Y., Prendergast, J. S. & Old, L. J. Proc. natn. Acad. Sci. U.S.A. 80, 5397–5401 (1983).
Blattner, F. R. et al. Science 196, 161–169 (1977).
Lawn, R. M., Fritsch, E. F., Parker, R. C., Blake, G. & Maniatis, T. Cell 15, 1157–1174 (1978).
Maniatis, T., Jeffrey, A. & Kleid, D. G. Proc. natn. Acad. Sci. U.S.A. 72, 1184–1188 (1975).
Rigby, P. W. J., Dieckmann, M., Rhodes, C. & Berg, P. J. molec. Biol. 113, 237–251 (1977).
Thomas, M. & Davis, R. W. J. molec. Biol. 91, 315–328 (1975).
Davis, R. W., Botstein, D. & Roth, J. R. (eds) Advanced Bacterial Genetics, 106–107 (Cold Spring Harbor, New York, 1980).
Messing, J. Meth. Enzym. 101, 20–78 (1983).
Maxam, A. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 74, 560–564 (1977).
Winzler, R. J. in Hormonal Proteins and Peptides (ed. Li, C. H.) 1–5 (Academic, New York, 1973).
Amann, E., Brosius, J. & Ptashne, M. Gene 25, 167–178 (1983).
Corbett, T. H., Griswold, D. P., Roberts, B. J., Peckham, J. C. & Schabel, F. M. Cancer Chemother. Rep. (Pt. 2) 5, 169–186 (1975).
Corbett, T. H., Griswold, D. P., Roberts, B. J., Peckham, J. C. & Schabel, F. M. Cancer 40, 2660–2680 (1977).
Clark, I. A., Virelizier, J-L., Carswell, E. A. & Wood, P. R. Infect. Immun. 32, 1058–1066 (1981).
Taverne, J., Dockrell, H. M. & Playfair, J. H. L. Infect. Immun. 33, 83–89 (1981).
Taverne, J., Depledge, P. & Playfair, J. H. L. Infect. Immun. 37, 927–934 (1982).
Playfair, J. H. L., Taverne, J. & Matthews, N. Immun. Today 5, 165–166 (1984).
Vieira, J. & Messing, J. Gene 19, 259–268 (1982).
Ito, H., Ike, Y., Ikuta, S. & Itakura, K. Nucleic Acids Res. 10, 1755–1769 (1982).
Ruff, M. R. & Gifford, G. E. J. Immun. 125, 1671–1677 (1980).
Laemmli, U. K. Nature 227, 680–685 (1970).
Isoelectric Focussing: Principles and Methods (User's manual) (Pharmacia Fine Chemicals, Sweden, 1982).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Shirai, T., Yamaguchi, H., Ito, H. et al. Cloning and expression in Escherichia coli of the gene for human tumour necrosis factor. Nature 313, 803–806 (1985). https://doi.org/10.1038/313803a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/313803a0
This article is cited by
-
Mitigation of Colitis with NovaSil Clay Therapy
Digestive Diseases and Sciences (2015)
-
Molecular cloning and characterization of tumour necrosis factor alpha (TNF‐α) from the Australian common brushtail possum, Trichosurus vulpecula
Immunology & Cell Biology (1996)
-
Inhibition of Cytokine Processing as a Therapeutic Strategy in Inflammation
Clinical Immunotherapeutics (1996)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.