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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1991 Feb 1;173(2):519–522. doi: 10.1084/jem.173.2.519

Autonomous growth and tumorigenicity induced by P40/interleukin 9 cDNA transfection of a mouse P40-dependent T cell line

PMCID: PMC2118792  PMID: 1899107

Abstract

To test the transforming potential of deregulated P40/Interleukin 9 expression, we transfected a mouse P40-dependent T cell line with P40 cDNA, and examined the tumorigenicity of the resulting transfectants. When the cells, which grew autonomously in vitro, were injected intraperitoneally or subcutaneously into syngeneic mice, a very high tumor incidence was observed with as few as 10(4) cells per inoculum. Animals died as a result of widespread dissemination of lymphomatous tissue to abdominal and thoracic organs. The same P40-dependent cell line transfected with a control construct did not form tumors even after injection of 10(7) cells. These results indicate that uncontrolled expression of P40 can support T cell proliferation in vivo, and may be a transforming event involved in the development of certain T cell tumors.

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Selected References

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  1. Blankenstein T., Li W. Q., Müller W., Diamantstein T. Retroviral interleukin 4 gene transfer into an interleukin 4-dependent cell line results in autocrine growth but not in tumorigenicity. Eur J Immunol. 1990 Apr;20(4):935–938. doi: 10.1002/eji.1830200433. [DOI] [PubMed] [Google Scholar]
  2. Donahue R. E., Yang Y. C., Clark S. C. Human P40 T-cell growth factor (interleukin-9) supports erythroid colony formation. Blood. 1990 Jun 15;75(12):2271–2275. [PubMed] [Google Scholar]
  3. Dunbar C. E., Browder T. M., Abrams J. S., Nienhuis A. W. COOH-terminal-modified interleukin-3 is retained intracellularly and stimulates autocrine growth. Science. 1989 Sep 29;245(4925):1493–1496. doi: 10.1126/science.2789432. [DOI] [PubMed] [Google Scholar]
  4. Hültner L., Druez C., Moeller J., Uyttenhove C., Schmitt E., Rüde E., Dörmer P., Van Snick J. Mast cell growth-enhancing activity (MEA) is structurally related and functionally identical to the novel mouse T cell growth factor P40/TCGFIII (interleukin 9). Eur J Immunol. 1990 Jun;20(6):1413–1416. doi: 10.1002/eji.1830200632. [DOI] [PubMed] [Google Scholar]
  5. Karasuyama H., Tohyama N., Tada T. Autocrine growth and tumorigenicity of interleukin 2-dependent helper T cells transfected with IL-2 gene. J Exp Med. 1989 Jan 1;169(1):13–25. doi: 10.1084/jem.169.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lang R. A., Metcalf D., Gough N. M., Dunn A. R., Gonda T. J. Expression of a hemopoietic growth factor cDNA in a factor-dependent cell line results in autonomous growth and tumorigenicity. Cell. 1985 Dec;43(2 Pt 1):531–542. doi: 10.1016/0092-8674(85)90182-5. [DOI] [PubMed] [Google Scholar]
  7. Ohara J., Paul W. E. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. doi: 10.1038/315333a0. [DOI] [PubMed] [Google Scholar]
  8. Renauld J. C., Goethals A., Houssiau F., Van Roost E., Van Snick J. Cloning and expression of a cDNA for the human homolog of mouse T cell and mast cell growth factor P40. Cytokine. 1990 Jan;2(1):9–12. doi: 10.1016/1043-4666(90)90037-t. [DOI] [PubMed] [Google Scholar]
  9. Schmitt E., Van Brandwijk R., Van Snick J., Siebold B., Rüde E. TCGF III/P40 is produced by naive murine CD4+ T cells but is not a general T cell growth factor. Eur J Immunol. 1989 Nov;19(11):2167–2170. doi: 10.1002/eji.1830191130. [DOI] [PubMed] [Google Scholar]
  10. Suda T., Murray R., Fischer M., Yokota T., Zlotnik A. Tumor necrosis factor-alpha and P40 induce day 15 murine fetal thymocyte proliferation in combination with IL-2. J Immunol. 1990 Mar 1;144(5):1783–1787. [PubMed] [Google Scholar]
  11. Tepper R. I., Pattengale P. K., Leder P. Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell. 1989 May 5;57(3):503–512. doi: 10.1016/0092-8674(89)90925-2. [DOI] [PubMed] [Google Scholar]
  12. Van Snick J., Goethals A., Renauld J. C., Van Roost E., Uyttenhove C., Rubira M. R., Moritz R. L., Simpson R. J. Cloning and characterization of a cDNA for a new mouse T cell growth factor (P40). J Exp Med. 1989 Jan 1;169(1):363–368. doi: 10.1084/jem.169.1.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Williams D. E., Morrissey P. J., Mochizuki D. Y., de Vries P., Anderson D., Cosman D., Boswell H. S., Cooper S., Grabstein K. H., Broxmeyer H. E. T-cell growth factor P40 promotes the proliferation of myeloid cell lines and enhances erythroid burst formation by normal murine bone marrow cells in vitro. Blood. 1990 Sep 1;76(5):906–911. [PubMed] [Google Scholar]
  14. Yamada G., Kitamura Y., Sonoda H., Harada H., Taki S., Mulligan R. C., Osawa H., Diamantstein T., Yokoyama S., Taniguchi T. Retroviral expression of the human IL-2 gene in a murine T cell line results in cell growth autonomy and tumorigenicity. EMBO J. 1987 Sep;6(9):2705–2709. doi: 10.1002/j.1460-2075.1987.tb02563.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Yang Y. C., Ricciardi S., Ciarletta A., Calvetti J., Kelleher K., Clark S. C. Expression cloning of cDNA encoding a novel human hematopoietic growth factor: human homologue of murine T-cell growth factor P40. Blood. 1989 Nov 1;74(6):1880–1884. [PubMed] [Google Scholar]

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