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. 1992 Jan 1;89(1):232–235. doi: 10.1073/pnas.89.1.232

Generation of plasmacytomas with the chromosomal translocation t(12;15) in interleukin 6 transgenic mice.

S Suematsu 1, T Matsusaka 1, T Matsuda 1, S Ohno 1, J Miyazaki 1, K Yamamura 1, T Hirano 1, T Kishimoto 1
PMCID: PMC48210  PMID: 1729694

Abstract

The mechanisms through which pristane or mineral oil can induce plasmacytomas in BALB/c or NZB mice are not fully understood, but involvement of interleukin 6 (IL-6), a growth factor for plasmacytomas and myelomas, has been strongly suggested. To clarify the role of IL-6 in plasmacytomagenesis, a human IL-6 cDNA was introduced into mouse germ lines under the transcriptional control of the murine major histocompatibility complex class I (H-2Ld) promoter. IL-6 transgenic mice of C57BL/6 origin developed a massive plasmacytosis but not plasmacytomas. However, introduction of BALB/c genetic background into IL-6 transgenic mice could generate monoclonal transplantable plasmacytomas with the chromosomal translocation t(12;15). These results provide firm evidence of the critical role of IL-6 in the plasmacytoma development.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cross M., Dexter T. M. Growth factors in development, transformation, and tumorigenesis. Cell. 1991 Jan 25;64(2):271–280. doi: 10.1016/0092-8674(91)90638-f. [DOI] [PubMed] [Google Scholar]
  2. Hayday A. C., Gillies S. D., Saito H., Wood C., Wiman K., Hayward W. S., Tonegawa S. Activation of a translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus. 1984 Jan 26-Feb 1Nature. 307(5949):334–340. doi: 10.1038/307334a0. [DOI] [PubMed] [Google Scholar]
  3. Heldin C. H., Westermark B. Growth factors as transforming proteins. Eur J Biochem. 1989 Oct 1;184(3):487–496. doi: 10.1111/j.1432-1033.1989.tb15041.x. [DOI] [PubMed] [Google Scholar]
  4. Hirano T., Akira S., Taga T., Kishimoto T. Biological and clinical aspects of interleukin 6. Immunol Today. 1990 Dec;11(12):443–449. doi: 10.1016/0167-5699(90)90173-7. [DOI] [PubMed] [Google Scholar]
  5. Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T., Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature. 1986 Nov 6;324(6092):73–76. doi: 10.1038/324073a0. [DOI] [PubMed] [Google Scholar]
  6. Jhappan C., Stahle C., Harkins R. N., Fausto N., Smith G. H., Merlino G. T. TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell. 1990 Jun 15;61(6):1137–1146. doi: 10.1016/0092-8674(90)90076-q. [DOI] [PubMed] [Google Scholar]
  7. Landias D., Beck B. N., Buerstedde J. M., Degraw S., Klein D., Koch N., Murphy D., Pierres M., Tada T., Yamamoto K. The assignment of chain specificities for anti-Ia monoclonal antibodies using L cell transfectants. J Immunol. 1986 Nov 1;137(9):3002–3005. [PubMed] [Google Scholar]
  8. Lang R. A., Metcalf D., Cuthbertson R. A., Lyons I., Stanley E., Kelso A., Kannourakis G., Williamson D. J., Klintworth G. K., Gonda T. J. Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage. Cell. 1987 Nov 20;51(4):675–686. doi: 10.1016/0092-8674(87)90136-x. [DOI] [PubMed] [Google Scholar]
  9. Matsuda T., Hirano T., Kishimoto T. Establishment of an interleukin 6 (IL 6)/B cell stimulatory factor 2-dependent cell line and preparation of anti-IL 6 monoclonal antibodies. Eur J Immunol. 1988 Jun;18(6):951–956. doi: 10.1002/eji.1830180618. [DOI] [PubMed] [Google Scholar]
  10. Matsui Y., Halter S. A., Holt J. T., Hogan B. L., Coffey R. J. Development of mammary hyperplasia and neoplasia in MMTV-TGF alpha transgenic mice. Cell. 1990 Jun 15;61(6):1147–1155. doi: 10.1016/0092-8674(90)90077-r. [DOI] [PubMed] [Google Scholar]
  11. Miyazaki J., Appella E., Ozato K. Negative regulation of the major histocompatibility class I gene in undifferentiated embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9537–9541. doi: 10.1073/pnas.83.24.9537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nordan R. P., Potter M. A macrophage-derived factor required by plasmacytomas for survival and proliferation in vitro. Science. 1986 Aug 1;233(4763):566–569. doi: 10.1126/science.3726549. [DOI] [PubMed] [Google Scholar]
  13. Ohno S., Babonits M., Wiener F., Spira J., Klein G., Potter M. Nonrandom chromosome changes involving the Ig gene-carrying chromosomes 12 and 6 in pristane-induced mouse plasmacytomas. Cell. 1979 Dec;18(4):1001–1007. doi: 10.1016/0092-8674(79)90212-5. [DOI] [PubMed] [Google Scholar]
  14. Ohno S., Migita S., Wiener F., Babonits M., Klein G., Mushinski J. F., Potter M. Chromosomal translocations activating myc sequences and transduction of v-abl are critical events in the rapid induction of plasmacytomas by pristane and abelson virus. J Exp Med. 1984 Jun 1;159(6):1762–1777. doi: 10.1084/jem.159.6.1762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. POTTER M., BOYCE C. R. Induction of plasma-cell neoplasms in strain BALB/c mice with mineral oil and mineral oil adjuvants. Nature. 1962 Mar 17;193:1086–1087. doi: 10.1038/1931086a0. [DOI] [PubMed] [Google Scholar]
  16. Potter M., Mushinski J. F., Mushinski E. B., Brust S., Wax J. S., Wiener F., Babonits M., Rapp U. R., Morse H. C., 3rd Avian v-myc replaces chromosomal translocation in murine plasmacytomagenesis. Science. 1987 Feb 13;235(4790):787–789. doi: 10.1126/science.3810165. [DOI] [PubMed] [Google Scholar]
  17. Rosenbaum H., Harris A. W., Bath M. L., McNeall J., Webb E., Adams J. M., Cory S. An E mu-v-abl transgene elicits plasmacytomas in concert with an activated myc gene. EMBO J. 1990 Mar;9(3):897–905. doi: 10.1002/j.1460-2075.1990.tb08187.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sandgren E. P., Luetteke N. C., Palmiter R. D., Brinster R. L., Lee D. C. Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell. 1990 Jun 15;61(6):1121–1135. doi: 10.1016/0092-8674(90)90075-p. [DOI] [PubMed] [Google Scholar]
  19. Suematsu S., Matsuda T., Aozasa K., Akira S., Nakano N., Ohno S., Miyazaki J., Yamamura K., Hirano T., Kishimoto T. IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7547–7551. doi: 10.1073/pnas.86.19.7547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Van Damme J., Opdenakker G., Simpson R. J., Rubira M. R., Cayphas S., Vink A., Billiau A., Van Snick J. Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor. J Exp Med. 1987 Mar 1;165(3):914–919. doi: 10.1084/jem.165.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Van Snick J., Cayphas S., Szikora J. P., Renauld J. C., Van Roost E., Boon T., Simpson R. J. cDNA cloning of murine interleukin-HP1: homology with human interleukin 6. Eur J Immunol. 1988 Feb;18(2):193–197. doi: 10.1002/eji.1830180202. [DOI] [PubMed] [Google Scholar]
  22. Yamamura K., Kikutani H., Takahashi N., Taga T., Akira S., Kawai K., Fukuchi K., Kumahara Y., Honjo T., Kishimoto T. Introduction of human gamma 1 immunoglobulin genes into fertilized mouse eggs. J Biochem. 1984 Aug;96(2):357–363. doi: 10.1093/oxfordjournals.jbchem.a134845. [DOI] [PubMed] [Google Scholar]

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