Abstract
The expression of p53 has been evaluated during oncogenesis of the pancreatic beta cells in transgenic mice harboring hybrid insulin-SV40 T antigen genes. Significant levels of p53 are detected in all cells expressing large T antigen. In contrast, the protein is undetectable in normal beta cells. There is a complete correspondence between the onset of expression of T antigen and the appearance of the endogenous p53 protein. In tumors, the two proteins are found in a complex. In addition, free uncomplexed T antigen is detected in every cell which expresses the transgene. These results are consistent with the participation of p53 in T antigen-induced tumorigenesis in vivo. The early appearance of p53 in all beta cells expressing large T cannot readily explain the progression of a small fraction of these cells into solid tumors.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adams T. E., Alpert S., Hanahan D. Non-tolerance and autoantibodies to a transgenic self antigen expressed in pancreatic beta cells. Nature. 1987 Jan 15;325(6101):223–228. doi: 10.1038/325223a0. [DOI] [PubMed] [Google Scholar]
- Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baekkeskov S., Landin M., Kristensen J. K., Srikanta S., Bruining G. J., Mandrup-Poulsen T., de Beaufort C., Soeldner J. S., Eisenbarth G., Lindgren F. Antibodies to a 64,000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes. J Clin Invest. 1987 Mar;79(3):926–934. doi: 10.1172/JCI112903. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bienz B., Zakut-Houri R., Givol D., Oren M. Analysis of the gene coding for the murine cellular tumour antigen p53. EMBO J. 1984 Sep;3(9):2179–2183. doi: 10.1002/j.1460-2075.1984.tb02110.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bishop J. M. Viral oncogenes. Cell. 1985 Aug;42(1):23–38. doi: 10.1016/s0092-8674(85)80098-2. [DOI] [PubMed] [Google Scholar]
- Coleman D. L. Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia. 1978 Mar;14(3):141–148. doi: 10.1007/BF00429772. [DOI] [PubMed] [Google Scholar]
- Crawford L. V., Lane D. P., Denhardt D. T., Harlow E. E., Nicklin P. M., Osborn K., Pim D. C. Characterization of the complex between SV40 large T antigen and the 53K host protein in transformed mouse cells. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):179–187. doi: 10.1101/sqb.1980.044.01.021. [DOI] [PubMed] [Google Scholar]
- Crawford L. The 53,000-dalton cellular protein and its role in transformation. Int Rev Exp Pathol. 1983;25:1–50. [PubMed] [Google Scholar]
- Deppert W., Haug M. Evidence for free and metabolically stable p53 protein in nuclear subfractions of simian virus 40-transformed cells. Mol Cell Biol. 1986 Jun;6(6):2233–2240. doi: 10.1128/mcb.6.6.2233. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Efrat S., Hanahan D. Bidirectional activity of the rat insulin II 5'-flanking region in transgenic mice. Mol Cell Biol. 1987 Jan;7(1):192–198. doi: 10.1128/mcb.7.1.192. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eliyahu D., Raz A., Gruss P., Givol D., Oren M. Participation of p53 cellular tumour antigen in transformation of normal embryonic cells. Nature. 1984 Dec 13;312(5995):646–649. doi: 10.1038/312646a0. [DOI] [PubMed] [Google Scholar]
- Hanahan D. Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature. 1985 May 9;315(6015):115–122. doi: 10.1038/315115a0. [DOI] [PubMed] [Google Scholar]
- Harlow E., Crawford L. V., Pim D. C., Williamson N. M. Monoclonal antibodies specific for simian virus 40 tumor antigens. J Virol. 1981 Sep;39(3):861–869. doi: 10.1128/jvi.39.3.861-869.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hellerström C. The life story of the pancreatic B cell. Diabetologia. 1984 Jun;26(6):393–400. doi: 10.1007/BF00262208. [DOI] [PubMed] [Google Scholar]
- Jay G., DeLeo A. B., Appella E., Dubois G. C., Law L. W., Khoury G., Old L. J. A common transformation-related protein in murine sarcomas and leukemias. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):659–664. doi: 10.1101/sqb.1980.044.01.069. [DOI] [PubMed] [Google Scholar]
- 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]
- Lane D. P., Simanis V., Bartsch R., Yewdell J., Gannon J., Mole S. Cellular targets for SV40 large T-antigen. Proc R Soc Lond B Biol Sci. 1985 Oct 22;226(1242):25–42. doi: 10.1098/rspb.1985.0077. [DOI] [PubMed] [Google Scholar]
- McCormick F., Harlow E. Association of a murine 53,000-dalton phosphoprotein with simian virus 40 large-T antigen in transformed cells. J Virol. 1980 Apr;34(1):213–224. doi: 10.1128/jvi.34.1.213-224.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mercer W. E., Avignolo C., Baserga R. Role of the p53 protein in cell proliferation as studied by microinjection of monoclonal antibodies. Mol Cell Biol. 1984 Feb;4(2):276–281. doi: 10.1128/mcb.4.2.276. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Milner J., Milner S. SV40-53K antigen: a possible role for 53K in normal cells. Virology. 1981 Jul 30;112(2):785–788. doi: 10.1016/0042-6822(81)90327-5. [DOI] [PubMed] [Google Scholar]
- Oren M., Bienz B., Givol D., Rechavi G., Zakut R. Analysis of recombinant DNA clones specific for the murine p53 cellular tumor antigen. EMBO J. 1983;2(10):1633–1639. doi: 10.1002/j.1460-2075.1983.tb01637.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oren M., Maltzman W., Levine A. J. Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells. Mol Cell Biol. 1981 Feb;1(2):101–110. doi: 10.1128/mcb.1.2.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oren M. The p53 cellular tumor antigen: gene structure, expression and protein properties. Biochim Biophys Acta. 1985 Nov 12;823(1):67–78. doi: 10.1016/0304-419x(85)90015-0. [DOI] [PubMed] [Google Scholar]
- Palmiter R. D., Brinster R. L. Germ-line transformation of mice. Annu Rev Genet. 1986;20:465–499. doi: 10.1146/annurev.ge.20.120186.002341. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parada L. F., Land H., Weinberg R. A., Wolf D., Rotter V. Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation. Nature. 1984 Dec 13;312(5995):649–651. doi: 10.1038/312649a0. [DOI] [PubMed] [Google Scholar]
- Reich N. C., Levine A. J. Growth regulation of a cellular tumour antigen, p53, in nontransformed cells. Nature. 1984 Mar 8;308(5955):199–201. doi: 10.1038/308199a0. [DOI] [PubMed] [Google Scholar]
- Rogel A., Popliker M., Webb C. G., Oren M. p53 cellular tumor antigen: analysis of mRNA levels in normal adult tissues, embryos, and tumors. Mol Cell Biol. 1985 Oct;5(10):2851–2855. doi: 10.1128/mcb.5.10.2851. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rotter V., Wolf D. Biological and molecular analysis of p53 cellular-encoded tumor antigen. Adv Cancer Res. 1985;43:113–141. doi: 10.1016/s0065-230x(08)60944-6. [DOI] [PubMed] [Google Scholar]
- Steffes M. W., Nielsen O., Dyrberg T., Baekkeskov S., Scott J., Lernmark A. Islet transplantation in mice differing in the I and S subregions of the H-2 complex. Transplantation. 1981 Jun;31(6):476–479. doi: 10.1097/00007890-198106000-00017. [DOI] [PubMed] [Google Scholar]
- Weinberg R. A. The action of oncogenes in the cytoplasm and nucleus. Science. 1985 Nov 15;230(4727):770–776. doi: 10.1126/science.2997917. [DOI] [PubMed] [Google Scholar]
- Yewdell J. W., Gannon J. V., Lane D. P. Monoclonal antibody analysis of p53 expression in normal and transformed cells. J Virol. 1986 Aug;59(2):444–452. doi: 10.1128/jvi.59.2.444-452.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]