Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1984 Apr;3(4):913–917. doi: 10.1002/j.1460-2075.1984.tb01905.x

Three different activated ras genes in mouse tumours; evidence for oncogene activation during progression of a mouse lymphoma.

K H Vousden, C J Marshall
PMCID: PMC557447  PMID: 6327295

Abstract

Five unrelated mouse tumours have been shown to carry activated transforming genes using the NIH/3T3 transfection assay. Three of these tumours, a T-cell lymphoma, a fibrosarcoma and a macrophage tumour, were found to carry an activated c-Ki-ras gene. A c-Ha-ras gene was shown to be activated in a myeloid leukaemia and a recently identified member of the 'ras' gene family, N-ras, was found to be activated in a lung carcinoma. The T-cell lymphoma, L5178Y-ES, is a more aggressively growing metastatic variant which arose spontaneously from the parental tumour, L5178Y-E. Although DNA from both parental and variant tumours was shown to transfer a genetic marker to recipient cells equally well, only the metastatic variant carried an activated c-Ki-ras gene detectable by transfection. The altered growth behaviour of the L5178Y-ES cells may therefore be the result of the spontaneous activation of the c-Ki-ras gene after the lymphoma cells had already become tumorigenic.

Full text

PDF
913

Images in this article

915Fig. 1.
on p.915
916Fig. 2.
on p.916
916Fig. 3.
on p.916
916Fig. 4.
on p.916

Selected References

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

  1. Balmain A., Pragnell I. B. Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene. Nature. 1983 May 5;303(5912):72–74. doi: 10.1038/303072a0. [DOI] [PubMed] [Google Scholar]
  2. Chang E. H., Gonda M. A., Ellis R. W., Scolnick E. M., Lowy D. R. Human genome contains four genes homologous to transforming genes of Harvey and Kirsten murine sarcoma viruses. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4848–4852. doi: 10.1073/pnas.79.16.4848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cooper G. M. Cellular transforming genes. Science. 1982 Aug 27;217(4562):801–806. doi: 10.1126/science.6285471. [DOI] [PubMed] [Google Scholar]
  4. Dale B., Ozanne B. Characterization of mouse cellular deoxyribonucleic acid homologous to Abelson murine leukemia virus-specific sequences. Mol Cell Biol. 1981 Aug;1(8):731–742. doi: 10.1128/mcb.1.8.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DeFeo D., Gonda M. A., Young H. A., Chang E. H., Lowy D. R., Scolnick E. M., Ellis R. W. Analysis of two divergent rat genomic clones homologous to the transforming gene of Harvey murine sarcoma virus. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3328–3332. doi: 10.1073/pnas.78.6.3328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Der C. J., Krontiris T. G., Cooper G. M. Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3637–3640. doi: 10.1073/pnas.79.11.3637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ellis R. W., DeFeo D., Maryak J. M., Young H. A., Shih T. Y., Chang E. H., Lowy D. R., Scolnick E. M. Dual evolutionary origin for the rat genetic sequences of Harvey murine sarcoma virus. J Virol. 1980 Nov;36(2):408–420. doi: 10.1128/jvi.36.2.408-420.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ellis R. W., Defeo D., Shih T. Y., Gonda M. A., Young H. A., Tsuchida N., Lowy D. R., Scolnick E. M. The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes. Nature. 1981 Aug 6;292(5823):506–511. doi: 10.1038/292506a0. [DOI] [PubMed] [Google Scholar]
  9. Eva A., Aaronson S. A. Frequent activation of c-kis as a transforming gene in fibrosarcomas induced by methylcholanthrene. Science. 1983 May 27;220(4600):955–956. doi: 10.1126/science.6302839. [DOI] [PubMed] [Google Scholar]
  10. Eva A., Tronick S. R., Gol R. A., Pierce J. H., Aaronson S. A. Transforming genes of human hematopoietic tumors: frequent detection of ras-related oncogenes whose activation appears to be independent of tumor phenotype. Proc Natl Acad Sci U S A. 1983 Aug;80(16):4926–4930. doi: 10.1073/pnas.80.16.4926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hall A., Marshall C. J., Spurr N. K., Weiss R. A. Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1. Nature. 1983 Jun 2;303(5916):396–400. doi: 10.1038/303396a0. [DOI] [PubMed] [Google Scholar]
  12. Harris A. W., Reynolds E. C., Finch L. R. Effect of thymidine on the sensitivity of cultured mouse tumor cells to 1-beta-D-arabinofuranosylcytosine. Cancer Res. 1979 Feb;39(2 Pt 1):538–541. [PubMed] [Google Scholar]
  13. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  14. Lane M. A., Neary D., Cooper G. M. Activation of a cellular transforming gene in tumours induced by Abelson murine leukaemia virus. Nature. 1982 Dec 16;300(5893):659–661. doi: 10.1038/300659a0. [DOI] [PubMed] [Google Scholar]
  15. Mantovani A. Effects on in vitro tumor growth of murine macrophages isolated from sarcoma lines differing in immunogenicity and metastasizing capacity. Int J Cancer. 1978 Dec;22(6):741–746. doi: 10.1002/ijc.2910220617. [DOI] [PubMed] [Google Scholar]
  16. Marshall C. J., Hall A., Weiss R. A. A transforming gene present in human sarcoma cell lines. Nature. 1982 Sep 9;299(5879):171–173. doi: 10.1038/299171a0. [DOI] [PubMed] [Google Scholar]
  17. McCoy M. S., Toole J. J., Cunningham J. M., Chang E. H., Lowy D. R., Weinberg R. A. Characterization of a human colon/lung carcinoma oncogene. Nature. 1983 Mar 3;302(5903):79–81. doi: 10.1038/302079a0. [DOI] [PubMed] [Google Scholar]
  18. Murray M. J., Cunningham J. M., Parada L. F., Dautry F., Lebowitz P., Weinberg R. A. The HL-60 transforming sequence: a ras oncogene coexisting with altered myc genes in hematopoietic tumors. Cell. 1983 Jul;33(3):749–757. doi: 10.1016/0092-8674(83)90017-x. [DOI] [PubMed] [Google Scholar]
  19. Newbold R. F., Overell R. W. Fibroblast immortality is a prerequisite for transformation by EJ c-Ha-ras oncogene. Nature. 1983 Aug 18;304(5927):648–651. doi: 10.1038/304648a0. [DOI] [PubMed] [Google Scholar]
  20. Parada L. F., Tabin C. J., Shih C., Weinberg R. A. Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene. Nature. 1982 Jun 10;297(5866):474–478. doi: 10.1038/297474a0. [DOI] [PubMed] [Google Scholar]
  21. Parr I. Response of syngeneic murine lymphomata to immunotherapy in relation to the antigenicity of the tumour. Br J Cancer. 1972 Jun;26(3):174–182. doi: 10.1038/bjc.1972.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Poste G., Fidler I. J. The pathogenesis of cancer metastasis. Nature. 1980 Jan 10;283(5743):139–146. doi: 10.1038/283139a0. [DOI] [PubMed] [Google Scholar]
  23. Pulciani S., Santos E., Lauver A. V., Long L. K., Aaronson S. A., Barbacid M. Oncogenes in solid human tumours. Nature. 1982 Dec 9;300(5892):539–542. doi: 10.1038/300539a0. [DOI] [PubMed] [Google Scholar]
  24. Rosenberg N. Abelson leukemia virus. Curr Top Microbiol Immunol. 1982;101:95–126. doi: 10.1007/978-3-642-68654-2_5. [DOI] [PubMed] [Google Scholar]
  25. Ruley H. E. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature. 1983 Aug 18;304(5927):602–606. doi: 10.1038/304602a0. [DOI] [PubMed] [Google Scholar]
  26. Santos E., Tronick S. R., Aaronson S. A., Pulciani S., Barbacid M. T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB- and Harvey-MSV transforming genes. Nature. 1982 Jul 22;298(5872):343–347. doi: 10.1038/298343a0. [DOI] [PubMed] [Google Scholar]
  27. Scher C. D., Siegler R. Direct transformation of 3T3 cells by Abelson murine leukaemia virus. Nature. 1975 Feb 27;253(5494):729–731. doi: 10.1038/253729a0. [DOI] [PubMed] [Google Scholar]
  28. Shih C., Padhy L. C., Murray M., Weinberg R. A. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature. 1981 Mar 19;290(5803):261–264. doi: 10.1038/290261a0. [DOI] [PubMed] [Google Scholar]
  29. Shih C., Shilo B. Z., Goldfarb M. P., Dannenberg A., Weinberg R. A. Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5714–5718. doi: 10.1073/pnas.76.11.5714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shimizu K., Goldfarb M., Perucho M., Wigler M. Isolation and preliminary characterization of the transforming gene of a human neuroblastoma cell line. Proc Natl Acad Sci U S A. 1983 Jan;80(2):383–387. doi: 10.1073/pnas.80.2.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  32. Sukumar S., Notario V., Martin-Zanca D., Barbacid M. Induction of mammary carcinomas in rats by nitroso-methylurea involves malignant activation of H-ras-1 locus by single point mutations. Nature. 1983 Dec 15;306(5944):658–661. doi: 10.1038/306658a0. [DOI] [PubMed] [Google Scholar]
  33. Wigler M., Pellicer A., Silverstein S., Axel R., Urlaub G., Chasin L. DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373–1376. doi: 10.1073/pnas.76.3.1373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yuasa Y., Srivastava S. K., Dunn C. Y., Rhim J. S., Reddy E. P., Aaronson S. A. Acquisition of transforming properties by alternative point mutations within c-bas/has human proto-oncogene. Nature. 1983 Jun 30;303(5920):775–779. doi: 10.1038/303775a0. [DOI] [PubMed] [Google Scholar]
  35. Ziegler S. F., Whitlock C. A., Goff S. P., Gifford A., Witte O. N. Lethal effect of the Abelson murine leukemia virus transforming gene product. Cell. 1981 Dec;27(3 Pt 2):477–486. doi: 10.1016/0092-8674(81)90389-5. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES