Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Jan 23;93(2):824–827. doi: 10.1073/pnas.93.2.824

Endogenous c-src as a determinant of the tumorigenicity of src oncogenes.

M S Halpern 1, J M England 1, G C Kopen 1, A A Christou 1, R L Taylor Jr 1
PMCID: PMC40141  PMID: 8570642

Abstract

We have compared the tumorigenicity of two src oncogenes, v-src and c-src(527), whose respective protein products pp60v-src and pp60c-src(527) show a different spectrum of amino acid substitutions vis-à-vis the c-src protooncogene-encoded product pp60c-src. Whereas the extent of primary tumor growth induced by c-src(527) was quite similar in the two chicken lines tested, the extent of v-src-induced tumor growth showed a marked line dependence. As examined with a line of chickens that shows immune-mediated regression of v-src-induced tumors, a weaker tumor immunity, as correlated with a greater level of primary tumor growth, resulted from inoculation of c-src(527) DNA than of v-src DNA. These observations indicated that the v-src-specific amino acid substitutions define a major tumor antigenicity. That a separate src-associated antigenicity is also targetable by the tumor immune response followed from the finding that the level of protective immunity against the growth of c-src(527) DNA-induced tumors was augmented under conditions of the prior regression of v-src DNA-induced tumors. As this latter antigenicity may include one or more c-src(527)-encoded peptides that are equivalent to c-src-encoded self peptides, these observations suggest that a host tolerance to pp60c-src can be broken so as to permit a tumor immune response based on recognition of self peptides of pp60c-src(527).

Full text

PDF
824

Selected References

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

  1. Cerasoli D. M., McGrath J., Carding S. R., Shih F. F., Knowles B. B., Caton A. J. Low avidity recognition of a class II-restricted neo-self peptide by virus-specific T cells. Int Immunol. 1995 Jun;7(6):935–945. doi: 10.1093/intimm/7.6.935. [DOI] [PubMed] [Google Scholar]
  2. Cotton P. C., Brugge J. S. Neural tissues express high levels of the cellular src gene product pp60c-src. Mol Cell Biol. 1983 Jun;3(6):1157–1162. doi: 10.1128/mcb.3.6.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fung Y. K., Crittenden L. B., Fadly A. M., Kung H. J. Tumor induction by direct injection of cloned v-src DNA into chickens. Proc Natl Acad Sci U S A. 1983 Jan;80(2):353–357. doi: 10.1073/pnas.80.2.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Halpern M. S., Ewert D. L., England J. M. Wing web or intravenous inoculation of chickens with v-src DNA induces visceral sarcomas. Virology. 1990 Mar;175(1):328–331. doi: 10.1016/0042-6822(90)90217-f. [DOI] [PubMed] [Google Scholar]
  5. Halpern M. S., Wisner T. W., Brown I. P., England J. M. Immune-based resistance to the formation of v-src-induced distal tumors. Virology. 1993 Nov;197(1):480–484. doi: 10.1006/viro.1993.1617. [DOI] [PubMed] [Google Scholar]
  6. Heath W. R., Allison J., Hoffmann M. W., Schönrich G., Hämmerling G., Arnold B., Miller J. F. Autoimmune diabetes as a consequence of locally produced interleukin-2. Nature. 1992 Oct 8;359(6395):547–549. doi: 10.1038/359547a0. [DOI] [PubMed] [Google Scholar]
  7. Johnson P. J., Coussens P. M., Danko A. V., Shalloway D. Overexpressed pp60c-src can induce focus formation without complete transformation of NIH 3T3 cells. Mol Cell Biol. 1985 May;5(5):1073–1083. doi: 10.1128/mcb.5.5.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kuzumaki N., Fujita H., Dosaka H., Katabami M., Levinson A. D. Transplantation resistance to a Rous sarcoma virus-induced tumor in mice immunized with v-src protein. J Natl Cancer Inst. 1988 Aug 17;80(12):959–962. doi: 10.1093/jnci/80.12.959. [DOI] [PubMed] [Google Scholar]
  9. Noguchi Y., Chen Y. T., Old L. J. A mouse mutant p53 product recognized by CD4+ and CD8+ T cells. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3171–3175. doi: 10.1073/pnas.91.8.3171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Nossal G. J. Negative selection of lymphocytes. Cell. 1994 Jan 28;76(2):229–239. doi: 10.1016/0092-8674(94)90331-x. [DOI] [PubMed] [Google Scholar]
  11. Plachý J., Hála K., Hejnar J., Geryk J., Svoboda J. src-specific immunity in inbred chickens bearing v-src DNA- and RSV-induced tumors. Immunogenetics. 1994;40(4):257–265. doi: 10.1007/BF00189970. [DOI] [PubMed] [Google Scholar]
  12. Stanbridge E. J., Nowell P. C. Origins of human cancer revisited. Cell. 1990 Nov 30;63(5):867–874. doi: 10.1016/0092-8674(90)90490-6. [DOI] [PubMed] [Google Scholar]
  13. Svoboda J., Plachý J., Hejnar J., Karakoz I., Guntaka R. V., Geryk J. Tumor induction by the LTR, v-src, LTR DNA in four B (MHC) congenic lines of chickens. Immunogenetics. 1992;35(5):309–315. doi: 10.1007/BF00189893. [DOI] [PubMed] [Google Scholar]
  14. Taylor R. L., Jr, Ewert D. L., England J. M., Halpern M. S. Major histocompatibility (B) complex control of the growth pattern of v-src DNA-induced primary tumors. Virology. 1992 Nov;191(1):477–479. doi: 10.1016/0042-6822(92)90214-a. [DOI] [PubMed] [Google Scholar]
  15. Wisner T. W., England J. M., Pan D. Y., Stoker A. W., Halpern M. S. Tumor immunity generated in the course of regression of v-src-induced sarcomas. J Virol. 1991 Dec;65(12):7020–7024. doi: 10.1128/jvi.65.12.7020-7024.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES