Abstract
Chicken embryo cells infected with partial transformation mutants of Rous sarcoma virus were tested for tumor-forming ability in chickens and in nude mice. Cells transformed by each of these partial transformation mutants display different combinations of transformation parameters. They therefore present a potentially favorable system for analyzing which properties of transformed cells are necessary for tumor formation. We found that the relative tumorigenicity of the virus mutants was generally similar in chickens and in nude mice, except that certain temperature-conditional mutants appeared to be sensitive to the differences in body temperature of the two experimental animals. (The body temperature of nude mice is 4 to 5 degrees C lower than that of chickens). Thus, the nude mouse appears to be a suitable system for testing the tumorigenicity of transformed chicken cells. Because mice are nonpermissive for Rous sarcoma virus infection and replication, it was possible to recover the transformed chicken cells from the tumors in this host and to determine what phenotypic changes they had undergone during tumor development. We also examined the relationship between various cellular properties of the virus-infected chicken cells in vitro and their tumorigenicity in nude mice. The combined results of these two studies indicated that anchorage independence and plasminogen activator production were highly correlated with the tumor-forming ability of these cells, whereas loss of fibronectin did not correlate with tumorigenicity. Furthermore, the inability of the least tumorigenic virus mutant to stimulate the phosphorylation of a 36,000-Mr target of pp60src raises the possibility that the 36,000-Mr protein plays a role in tumor formation.
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- 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]
- Becker D., Kurth R., Critchley D., Friis R., Bauer H. Distinguishable transformation-defective phenotypes among temperature-sensitive mutants of Rous sarcoma virus. J Virol. 1977 Mar;21(3):1042–1055. doi: 10.1128/jvi.21.3.1042-1055.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brugge J. S., Erikson R. L. Identification of a transformation-specific antigen induced by an avian sarcoma virus. Nature. 1977 Sep 22;269(5626):346–348. doi: 10.1038/269346a0. [DOI] [PubMed] [Google Scholar]
- Collett M. S., Erikson R. L. Protein kinase activity associated with the avian sarcoma virus src gene product. Proc Natl Acad Sci U S A. 1978 Apr;75(4):2021–2024. doi: 10.1073/pnas.75.4.2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collett M. S., Purchio A. F., Erikson R. L. Avian sarcoma virus-transforming protein, pp60src shows protein kinase activity specific for tyrosine. Nature. 1980 May 15;285(5761):167–169. doi: 10.1038/285167a0. [DOI] [PubMed] [Google Scholar]
- Eicher E. M., Washburn L. L. Assignment of genes to regions of mouse chromosomes. Proc Natl Acad Sci U S A. 1978 Feb;75(2):946–950. doi: 10.1073/pnas.75.2.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Erikson E., Erikson R. L. Identification of a cellular protein substrate phosphorylated by the avian sarcoma virus-transforming gene product. Cell. 1980 Oct;21(3):829–836. doi: 10.1016/0092-8674(80)90446-8. [DOI] [PubMed] [Google Scholar]
- Erikson R. L., Collett M. S., Erikson E., Purchio A. F. Evidence that the avian sarcoma virus transforming gene product is a cyclic AMP-independent protein kinase. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6260–6264. doi: 10.1073/pnas.76.12.6260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freedman V. H., Brown A. L., Klinger H. P., Shin S. I. Mass production of animal cells in nude mice with retention of cell specific markers. Exp Cell Res. 1976 Mar 1;98(1):143–151. doi: 10.1016/0014-4827(76)90473-0. [DOI] [PubMed] [Google Scholar]
- Hunter T., Sefton B. M. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1311–1315. doi: 10.1073/pnas.77.3.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kahn P., Shin S. I. Cellular tumorigenicity in nude mice. Test of associations among loss of cell-surface fibronectin, anchorage independence, and tumor-forming ability. J Cell Biol. 1979 Jul;82(1):1–16. doi: 10.1083/jcb.82.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kahn P., Simon R. S., Klein A. S., Shin S. Tumor formation by transformed cells in nude mice. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):695–702. doi: 10.1101/sqb.1980.044.01.074. [DOI] [PubMed] [Google Scholar]
- Kawai S., Duesberg P. H., Hanafusa H. Transformation-defective mutants of Rous sarcoma virus with src gene deletions of varying length. J Virol. 1977 Dec;24(3):910–914. doi: 10.1128/jvi.24.3.910-914.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kawai S., Hanafusa H. The effects of reciprocal changes in temperature on the transformed state of cells infected with a rous sarcoma virus mutant. Virology. 1971 Nov;46(2):470–479. doi: 10.1016/0042-6822(71)90047-x. [DOI] [PubMed] [Google Scholar]
- Khoury A. T., Hanafusa H. Synethesis and integration of viral DNA in chicken cells at different time after infection with various multiplicities of avian oncornavirus. J Virol. 1976 May;18(2):383–400. doi: 10.1128/jvi.18.2.383-400.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levinson A. D., Oppermann H., Levintow L., Varmus H. E., Bishop J. M. Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein. Cell. 1978 Oct;15(2):561–572. doi: 10.1016/0092-8674(78)90024-7. [DOI] [PubMed] [Google Scholar]
- Meera Khan P. Enzyme electrophoresis on cellulose acetate gel: zymogram patterns in mgh-mouse and man--Chinese hamster somatic cell hybrids. Arch Biochem Biophys. 1971 Aug;145(2):470–483. doi: 10.1016/s0003-9861(71)80007-3. [DOI] [PubMed] [Google Scholar]
- Purchio A. F., Erikson E., Brugge J. S., Erikson R. L. Identification of a polypeptide encoded by the avian sarcoma virus src gene. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1567–1571. doi: 10.1073/pnas.75.3.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Radke K., Gilmore T., Martin G. S. Transformation by Rous sarcoma virus: a cellular substrate for transformation-specific protein phosphorylation contains phosphotyrosine. Cell. 1980 Oct;21(3):821–828. doi: 10.1016/0092-8674(80)90445-6. [DOI] [PubMed] [Google Scholar]
- Radke K., Martin G. S. Transformation by Rous sarcoma virus: effects of src gene expression on the synthesis and phosphorylation of cellular polypeptides. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5212–5216. doi: 10.1073/pnas.76.10.5212. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reid L. M., Minato N., Gresser I., Holland J., Kadish A., Bloom B. R. Influence of anti-mouse interferon serum on the growth and metastasis of tumor cells persistently infected with virus and of human prostatic tumors in athymic nude mice. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1171–1175. doi: 10.1073/pnas.78.2.1171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sefton B. M., Hunter T., Beemon K., Eckhart W. Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus. Cell. 1980 Jul;20(3):807–816. doi: 10.1016/0092-8674(80)90327-x. [DOI] [PubMed] [Google Scholar]
- Shin S. I., Freedman V. H., Risser R., Pollack R. Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4435–4439. doi: 10.1073/pnas.72.11.4435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weber M. J., Friis R. R. Dissociation of transformation parameters using temperature-conditional mutants of Rous sarcoma virus. Cell. 1979 Jan;16(1):25–32. doi: 10.1016/0092-8674(79)90184-3. [DOI] [PubMed] [Google Scholar]
- Weber M. J. Hexose transport in normal and in Rous sarcoma virus-transformed cells. J Biol Chem. 1973 May 10;248(9):2978–2983. [PubMed] [Google Scholar]