Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1985 Sep;5(9):2204–2211. doi: 10.1128/mcb.5.9.2204

Differential transformation of C3H10T1/2 cells by v-mos: sequential expression of transformation parameters.

F A van der Hoorn, V Müller
PMCID: PMC366945  PMID: 3016522

Abstract

Extremely small quantities of the product of the transforming gene v-mos of Moloney murine sarcoma virus are able to efficiently transform cells. Recent data indicate the existence of a threshold level for v-mos transformation of NIH3T3 cells. Using mouse mammary tumor virus long terminal repeat sequences or hybrid promoters consisting of mouse mammary tumor virus and Moloney murine sarcoma virus long terminal repeat elements to express v-mos in C3H10T1/2 cells, we established cell lines representing different stages of morphological transformation in vitro. The threshold level for v-mos transformation was considerably lower than that for NIH3T3 cells, because no treatment with dexamethasone or primary selection other than transformation was necessary during standard transfection procedures. Using the cell lines mentioned we established an association of the level of v-mos expression with the transformation parameters examined, but not with p53 levels. Furthermore, the characterization of the different promoters showed (i) that the distal binding site confers hormone responsiveness to Moloney murine sarcoma virus promoter elements and (ii) that artifactual transcription initiation sites can be detected in mouse mammary tumor virus-Moloney murine sarcoma virus hybrid promoters which are, however, not regulated by the hormone.

Full text

PDF
2204

Images in this article

2206Image
on p.2206
2207Image
on p.2207
2208Image
on p.2208
2208Image
on p.2208

Selected References

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

  1. Anderson D. D., Beckmann R. P., Harms E. H., Nakamura K., Weber M. J. Biological properties of "partial" transformation mutants of Rous sarcoma virus and characterization of their pp60src kinase. J Virol. 1981 Jan;37(1):445–458. doi: 10.1128/jvi.37.1.445-458.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benoist C., Chambon P. In vivo sequence requirements of the SV40 early promotor region. Nature. 1981 Mar 26;290(5804):304–310. doi: 10.1038/290304a0. [DOI] [PubMed] [Google Scholar]
  3. Bishop J. M. Cellular oncogenes and retroviruses. Annu Rev Biochem. 1983;52:301–354. doi: 10.1146/annurev.bi.52.070183.001505. [DOI] [PubMed] [Google Scholar]
  4. Buetti E., Diggelmann H. Glucocorticoid regulation of mouse mammary tumor virus: identification of a short essential DNA region. EMBO J. 1983;2(8):1423–1429. doi: 10.1002/j.1460-2075.1983.tb01601.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chandler V. L., Maler B. A., Yamamoto K. R. DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo. Cell. 1983 Jun;33(2):489–499. doi: 10.1016/0092-8674(83)90430-0. [DOI] [PubMed] [Google Scholar]
  6. Colby W. W., Chen E. Y., Smith D. H., Levinson A. D. Identification and nucleotide sequence of a human locus homologous to the v-myc oncogene of avian myelocytomatosis virus MC29. Nature. 1983 Feb 24;301(5902):722–725. doi: 10.1038/301722a0. [DOI] [PubMed] [Google Scholar]
  7. Collins S., Groudine M. Amplification of endogenous myc-related DNA sequences in a human myeloid leukaemia cell line. Nature. 1982 Aug 12;298(5875):679–681. doi: 10.1038/298679a0. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Everett R. D. A detailed analysis of an HSV-1 early promoter: sequences involved in trans-activation by viral immediate-early gene products are not early-gene specific. Nucleic Acids Res. 1984 Apr 11;12(7):3037–3056. doi: 10.1093/nar/12.7.3037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fasel N., Pearson K., Buetti E., Diggelmann H. The region of mouse mammary tumor virus DNA containing the long terminal repeat includes a long coding sequence and signals for hormonally regulated transcription. EMBO J. 1982;1(1):3–7. doi: 10.1002/j.1460-2075.1982.tb01115.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Folkman J., Moscona A. Role of cell shape in growth control. Nature. 1978 Jun 1;273(5661):345–349. doi: 10.1038/273345a0. [DOI] [PubMed] [Google Scholar]
  12. Foster D. A., Hanafusa H. A fps gene without gag gene sequences transforms cells in culture and induces tumors in chickens. J Virol. 1983 Dec;48(3):744–751. doi: 10.1128/jvi.48.3.744-751.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Freedman V. H., Shin S. I. Cellular tumorigenicity in nude mice: correlation with cell growth in semi-solid medium. Cell. 1974 Dec;3(4):355–359. doi: 10.1016/0092-8674(74)90050-6. [DOI] [PubMed] [Google Scholar]
  14. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  15. Groner B., Hynes N. E. Number and location of mouse mammary tumor virus proviral DNA in mouse DNA of normal tissue and of mammary tumors. J Virol. 1980 Mar;33(3):1013–1025. doi: 10.1128/jvi.33.3.1013-1025.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hayward W. S., Neel B. G., Astrin S. M. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. doi: 10.1038/290475a0. [DOI] [PubMed] [Google Scholar]
  17. Heidelberger C. Chemical carcinogenesis. Annu Rev Biochem. 1975;44:79–121. doi: 10.1146/annurev.bi.44.070175.000455. [DOI] [PubMed] [Google Scholar]
  18. Huang A. L., Ostrowski M. C., Berard D., Hager G. L. Glucocorticoid regulation of the Ha-MuSV p21 gene conferred by sequences from mouse mammary tumor virus. Cell. 1981 Dec;27(2 Pt 1):245–255. doi: 10.1016/0092-8674(81)90408-6. [DOI] [PubMed] [Google Scholar]
  19. Iwashita S., Kitamura N., Yoshida M. Molecular events leading to fusiform morphological transformation by partial src deletion mutant of Rous sarcoma virus. Virology. 1983 Mar;125(2):419–431. doi: 10.1016/0042-6822(83)90213-1. [DOI] [PubMed] [Google Scholar]
  20. Jakobovits E. B., Majors J. E., Varmus H. E. Hormonal regulation of the Rous sarcoma virus src gene via a heterologous promoter defines a threshold dose for cellular transformation. Cell. 1984 Oct;38(3):757–765. doi: 10.1016/0092-8674(84)90271-x. [DOI] [PubMed] [Google Scholar]
  21. Jenkins J. R., Rudge K., Currie G. A. Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53. Nature. 1984 Dec 13;312(5995):651–654. doi: 10.1038/312651a0. [DOI] [PubMed] [Google Scholar]
  22. Jones M., Bosselman R. A., van der Hoorn F. A., Berns A., Fan H., Verma I. M. Identification and molecular cloning of Moloney mouse sarcoma virus-specific sequences from uninfected mouse cells. Proc Natl Acad Sci U S A. 1980 May;77(5):2651–2655. doi: 10.1073/pnas.77.5.2651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kaplan P. L., Ozanne B. Cellular responsiveness to growth factors correlates with a cell's ability to express the transformed phenotype. Cell. 1983 Jul;33(3):931–938. doi: 10.1016/0092-8674(83)90036-3. [DOI] [PubMed] [Google Scholar]
  24. Keath E. J., Caimi P. G., Cole M. D. Fibroblast lines expressing activated c-myc oncogenes are tumorigenic in nude mice and syngeneic animals. Cell. 1984 Dec;39(2 Pt 1):339–348. doi: 10.1016/0092-8674(84)90012-6. [DOI] [PubMed] [Google Scholar]
  25. Land H., Parada L. F., Weinberg R. A. Cellular oncogenes and multistep carcinogenesis. Science. 1983 Nov 18;222(4625):771–778. doi: 10.1126/science.6356358. [DOI] [PubMed] [Google Scholar]
  26. Lane D. P. Cell immortalization and transformation by the p53 gene. Nature. 1984 Dec 13;312(5995):596–597. doi: 10.1038/312596a0. [DOI] [PubMed] [Google Scholar]
  27. Langman R. E. Transformation and tumorigenesis. Nature. 1980 Jan 17;283(5744):246–248. doi: 10.1038/283246b0. [DOI] [PubMed] [Google Scholar]
  28. Lee F., Hall C. V., Ringold G. M., Dobson D. E., Luh J., Jacob P. E. Functional analysis of the steroid hormone control region of mouse mammary tumor virus. Nucleic Acids Res. 1984 May 25;12(10):4191–4206. doi: 10.1093/nar/12.10.4191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. McKnight S. L., Kingsbury R. Transcriptional control signals of a eukaryotic protein-coding gene. Science. 1982 Jul 23;217(4557):316–324. doi: 10.1126/science.6283634. [DOI] [PubMed] [Google Scholar]
  30. Mercer W. E., Nelson D., DeLeo A. B., Old L. J., Baserga R. Microinjection of monoclonal antibody to protein p53 inhibits serum-induced DNA synthesis in 3T3 cells. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6309–6312. doi: 10.1073/pnas.79.20.6309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
  32. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ostrowski M. C., Richard-Foy H., Wolford R. G., Berard D. S., Hager G. L. Glucocorticoid regulation of transcription at an amplified, episomal promoter. Mol Cell Biol. 1983 Nov;3(11):2045–2057. doi: 10.1128/mcb.3.11.2045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Papkoff J., Nigg E. A., Hunter T. The transforming protein of Moloney murine sarcoma virus is a soluble cytoplasmic protein. Cell. 1983 May;33(1):161–172. doi: 10.1016/0092-8674(83)90345-8. [DOI] [PubMed] [Google Scholar]
  35. Papkoff J., Ringold G. M. Use of the mouse mammary tumor virus long terminal repeat to promote steroid-inducible expression of v-mos. J Virol. 1984 Nov;52(2):420–430. doi: 10.1128/jvi.52.2.420-430.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Reznikoff C. A., Brankow D. W., Heidelberger C. Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res. 1973 Dec;33(12):3231–3238. [PubMed] [Google Scholar]
  37. Rotter V., Boss M. A., Baltimore D. Increased concentration of an apparently identical cellular protein in cells transformed by either Abelson murine leukemia virus or other transforming agents. J Virol. 1981 Apr;38(1):336–346. doi: 10.1128/jvi.38.1.336-346.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Scheidereit C., Beato M. Contacts between hormone receptor and DNA double helix within a glucocorticoid regulatory element of mouse mammary tumor virus. Proc Natl Acad Sci U S A. 1984 May;81(10):3029–3033. doi: 10.1073/pnas.81.10.3029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Slamon D. J., deKernion J. B., Verma I. M., Cline M. J. Expression of cellular oncogenes in human malignancies. Science. 1984 Apr 20;224(4646):256–262. doi: 10.1126/science.6538699. [DOI] [PubMed] [Google Scholar]
  40. Van Beveren C., van Straaten F., Galleshaw J. A., Verma I. M. Nucleotide sequence of the genome of a murine sarcoma virus. Cell. 1981 Nov;27(1 Pt 2):97–108. doi: 10.1016/0092-8674(81)90364-0. [DOI] [PubMed] [Google Scholar]
  41. Vennström B., Kahn P., Adkins B., Enrietto P., Hayman M. J., Graf T., Luciw P. Transformation of mammalian fibroblasts and macrophages in vitro by a murine retrovirus encoding an avian v-myc oncogene. EMBO J. 1984 Dec 20;3(13):3223–3229. doi: 10.1002/j.1460-2075.1984.tb02282.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. de Larco J. E., Todaro G. J. Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4001–4005. doi: 10.1073/pnas.75.8.4001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. van der Hoorn F. A., Hulsebos E., Berns A. J., Bloemers H. P. Molecularly cloned c-mos(rat) is biologically active. EMBO J. 1982;1(11):1313–1317. doi: 10.1002/j.1460-2075.1982.tb01316.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. van der Hoorn F. A., Saris C. J., Bloemers H. P. 3Y1 rat cells are defective in processing of the envelope precursor protein of AKR virus. Virology. 1983 Jan 30;124(2):462–466. doi: 10.1016/0042-6822(83)90361-6. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES