Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1973 Aug 1;138(2):364–372. doi: 10.1084/jem.138.2.364

MUTANTS OF NONPRODUCER CELL LINES TRANSFORMED BY MURINE SARCOMA VIRUS

II. RELATIONSHIP OF TUMORIGENICITY TO PRESENCE OF VIRAL MARKERS AND RESCUABLE SARCOMA GENOME

M Hatanaka 1, R Klein 1, C W Long 1, R Gilden 1
PMCID: PMC2139401  PMID: 4124209

Abstract

Tumorigenic and nontumorigenic mutants induced by a single 5'-bromodeoxyuridine (BrdU) treatment of a nonproducer (NP) tumorigenic cell line were isolated and characterized. Among the cloned derivatives were examples of virus-free and sarcoma virus-producing cell lines. Oncogenicity did not correlate with production of virus or ease of rescue of the sarcoma genome. All lines, including nononcogenic derivatives, retained the sarcoma genome. Phenotypic reversion of some cell mutants was observed after in vivo inoculation or long term in vitro cultivation. The M-50T cell line, obtained from a tumor induced by M-50 cells, had a sarcoma genome rescuable by direct superinfection; this was only achieved with parental M-50 cells by a cell fusion rescue technique. The M-43-2T cell, obtained from a single small static tumor induced by otherwise nononcogenic M-43-2 cells, shed sarcoma virus and became tumorigenic. M-58-4-48 became tumorigenic after passage 48 of the M-58-4 line, which was originally nontumorigenic. These observations of phenotypic reversion demonstrate that the presence of the sarcoma gene in cells is an essential but not sufficient condition of tumorigenesis.

Full Text

The Full Text of this article is available as a PDF (637.5 KB).

Selected References

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

  1. Aaronson S. A. Chemical induction of focus-forming virus from nonproducer cells transformed by murine sarcoma virus. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3069–3072. doi: 10.1073/pnas.68.12.3069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bassin R. H., Phillips L. A., Kramer M. J., Haapala D. K., Peebles P. T., Nomura S., Fischinger P. J. Transformation of mouse 3T3 cells by murine sarcoma virus: release of virus-like particles in the absence of replicating murine leukemia helper virus. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1520–1524. doi: 10.1073/pnas.68.7.1520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bassin R. H., Tuttle N., Fischinger P. J. Isolation of murine sarcoma virus-transformed mouse cells which are negative for leukemia virus from agar suspension cultures. Int J Cancer. 1970 Jul 15;6(1):95–107. doi: 10.1002/ijc.2910060114. [DOI] [PubMed] [Google Scholar]
  4. Fischinger P. J., Schaefer W., Seifert E. Detection of some murine leukemia virus antigens in virus particles derived from 3T3 cells transformed only by murine sarcoma virus. Virology. 1972 Jan;47(1):229–235. doi: 10.1016/0042-6822(72)90254-1. [DOI] [PubMed] [Google Scholar]
  5. Harris H., Miller O. J., Klein G., Worst P., Tachibana T. Suppression of malignancy by cell fusion. Nature. 1969 Jul 26;223(5204):363–368. doi: 10.1038/223363a0. [DOI] [PubMed] [Google Scholar]
  6. Hartley J. W., Rowe W. P., Capps W. I., Huebner R. J. Isolation of naturally occurring viruses of the murine leukemia virus group in tissue culture. J Virol. 1969 Feb;3(2):126–132. doi: 10.1128/jvi.3.2.126-132.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hartley J. W., Rowe W. P., Huebner R. J. Host-range restrictions of murine leukemia viruses in mouse embryo cell cultures. J Virol. 1970 Feb;5(2):221–225. doi: 10.1128/jvi.5.2.221-225.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hatanaka M., Klein R., Toni R., Walker J., Gilden R. Mutants of nonproducer cell lines transformed by murine sarcoma viruses. I. Induction, isolation, particle production, and tumorigenicity. J Exp Med. 1973 Aug 1;138(2):356–363. doi: 10.1084/jem.138.2.356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hitotsumachi S., Rabinowitz Z., Sachs L. Ciromosomal control of reversion in transformed cells. Nature. 1971 Jun 25;231(5304):511–514. doi: 10.1038/231511a0. [DOI] [PubMed] [Google Scholar]
  10. Huebner R. J., Hartley J. W., Rowe W. P., Lane W. T., Capps W. I. Rescue of the defective genome of Moloney sarcoma virus from a noninfectious hamster tumor and the production of pseudotype sarcoma viruses with various murine leukemia viruses. Proc Natl Acad Sci U S A. 1966 Oct;56(4):1164–1169. doi: 10.1073/pnas.56.4.1164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kelloff G. J., Hatanaka M., Gilden R. V. Assay of C-type virus infectivity by measurement of RNA-dependent DNA polymerase activity. Virology. 1972 Apr;48(1):266–269. doi: 10.1016/0042-6822(72)90135-3. [DOI] [PubMed] [Google Scholar]
  12. Kellogg G. J., Huebner R. J., Long C., Gilden R. V. Rapid rescue of the defective M-MSV genome by the use of cell fusion. Virology. 1971 Dec;46(3):965–968. doi: 10.1016/0042-6822(71)90098-5. [DOI] [PubMed] [Google Scholar]
  13. Nomura S., Fischinger P. J., Mattern C. F., Peebles P. T., Bassin R. H., Friedman G. P. Revertants of mouse cells transformed by murine sarcoma virus. I. Characterization of flat and transformed sublines without a rescuable murine sarcoma virus. Virology. 1972 Oct;50(1):51–64. doi: 10.1016/0042-6822(72)90345-5. [DOI] [PubMed] [Google Scholar]
  14. Pollack R., Wolman S., Vogel A. Reversion of virus-transformed cell lines: hyperploidy accompanies retention of viral genes. Nature. 1970 Dec 5;228(5275):938–passim. doi: 10.1038/228938a0. [DOI] [PubMed] [Google Scholar]
  15. Rabinowitz Z., Sachs L. Control of the reversion of properties in transformed cells. Nature. 1970 Jan 10;225(5228):136–139. doi: 10.1038/225136a0. [DOI] [PubMed] [Google Scholar]
  16. Rabinowitz Z., Sachs L. Reversion of properties in cells transformed by polyoma virus. Nature. 1968 Dec 21;220(5173):1203–1206. doi: 10.1038/2201203a0. [DOI] [PubMed] [Google Scholar]
  17. Rowe W. P., Pugh W. E., Hartley J. W. Plaque assay techniques for murine leukemia viruses. Virology. 1970 Dec;42(4):1136–1139. doi: 10.1016/0042-6822(70)90362-4. [DOI] [PubMed] [Google Scholar]
  18. Silagi S., Bruce S. A. Suppression of malignancy and differentiation in melanotic melanoma cells. Proc Natl Acad Sci U S A. 1970 May;66(1):72–78. doi: 10.1073/pnas.66.1.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Stephenson J. R., Scolnick E. M., Aaronson S. A. Genetic stability of the sarcoma viruses in murine and avian sarcoma virus-transformed nonproducer cells. Int J Cancer. 1972 May 15;9(3):577–583. doi: 10.1002/ijc.2910090314. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES