Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1985 Nov;52(5):687–693. doi: 10.1038/bjc.1985.244

Immunohistochemical detection of the ras oncogene p21 product in an experimental tumour and in human colorectal neoplasms.

A R Williams, J Piris, D A Spandidos, A H Wyllie
PMCID: PMC1977224  PMID: 3904801

Abstract

The monoclonal antibody Y13 259 to the ras oncogene protein product p21 was used in an immunohistochemical study of ras expression in human colorectal neoplasms. The ability of the antibody to detect enhanced levels of ras expression was confirmed by its use with an experimental neoplasm known to express ras at high levels. Human colonic adenocarcinomas in general showed a similar staining intensity to that seen in normal mucosa. Adenomas however showed consistently high p21 expression as indicated by staining intensity. This suggests that elevated ras expression may be important in the development of adenomas, but that high levels need not be sustained in the conversion to invasive carcinoma.

Full text

PDF
693

Images in this article

Selected References

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

  1. Balmain A., Ramsden M., Bowden G. T., Smith J. Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas. Nature. 1984 Feb 16;307(5952):658–660. doi: 10.1038/307658a0. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Bleiberg H., Galand P. In vitro autoradiographic determination of cell kinetic parameters in adenocarcinomas and adjacent healthy mucosa of the human colon and rectum. Cancer Res. 1976 Feb;36(2 Pt 1):325–328. [PubMed] [Google Scholar]
  4. Capon D. J., Chen E. Y., Levinson A. D., Seeburg P. H., Goeddel D. V. Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature. 1983 Mar 3;302(5903):33–37. doi: 10.1038/302033a0. [DOI] [PubMed] [Google Scholar]
  5. Capon D. J., Seeburg P. H., McGrath J. P., Hayflick J. S., Edman U., Levinson A. D., Goeddel D. V. Activation of Ki-ras2 gene in human colon and lung carcinomas by two different point mutations. Nature. 1983 Aug 11;304(5926):507–513. doi: 10.1038/304507a0. [DOI] [PubMed] [Google Scholar]
  6. Chang E. H., Furth M. E., Scolnick E. M., Lowy D. R. Tumorigenic transformation of mammalian cells induced by a normal human gene homologous to the oncogene of Harvey murine sarcoma virus. Nature. 1982 Jun 10;297(5866):479–483. doi: 10.1038/297479a0. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Deschner E. E., Lipkin M. Cell proliferation in normal, preneoplastic and neoplastic gastrointestinal cells. Clin Gastroenterol. 1976 Sep;5(3):543–561. [PubMed] [Google Scholar]
  10. Furth M. E., Davis L. J., Fleurdelys B., Scolnick E. M. Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and of the cellular ras gene family. J Virol. 1982 Jul;43(1):294–304. doi: 10.1128/jvi.43.1.294-304.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gallick G. E., Kurzrock R., Kloetzer W. S., Arlinghaus R. B., Gutterman J. U. Expression of p21ras in fresh primary and metastatic human colorectal tumors. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1795–1799. doi: 10.1073/pnas.82.6.1795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gibbs J. B., Sigal I. S., Poe M., Scolnick E. M. Intrinsic GTPase activity distinguishes normal and oncogenic ras p21 molecules. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5704–5708. doi: 10.1073/pnas.81.18.5704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hurley J. B., Simon M. I., Teplow D. B., Robishaw J. D., Gilman A. G. Homologies between signal transducing G proteins and ras gene products. Science. 1984 Nov 16;226(4676):860–862. doi: 10.1126/science.6436980. [DOI] [PubMed] [Google Scholar]
  14. Kamata T., Feramisco J. R. Epidermal growth factor stimulates guanine nucleotide binding activity and phosphorylation of ras oncogene proteins. Nature. 1984 Jul 12;310(5973):147–150. doi: 10.1038/310147a0. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. McGrath J. P., Capon D. J., Goeddel D. V., Levinson A. D. Comparative biochemical properties of normal and activated human ras p21 protein. Nature. 1984 Aug 23;310(5979):644–649. doi: 10.1038/310644a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Shih T. Y., Weeks M. O., Young H. A., Scholnick E. M. Identification of a sarcoma virus-coded phosphoprotein in nonproducer cells transformed by Kirsten or Harvey murine sarcoma virus. Virology. 1979 Jul 15;96(1):64–79. doi: 10.1016/0042-6822(79)90173-9. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Spandidos D. A., Agnantis N. J. Human malignant tumours of the breast, as compared to their respective normal tissue, have elevated expression of the Harvey ras oncogene. Anticancer Res. 1984 Jul-Oct;4(4-5):269–272. [PubMed] [Google Scholar]
  22. Spandidos D. A., Kerr I. B. Elevated expression of the human ras oncogene family in premalignant and malignant tumours of the colorectum. Br J Cancer. 1984 Jun;49(6):681–688. doi: 10.1038/bjc.1984.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Spandidos D. A., Lamothe A., Field J. K. Multiple transcriptional activation of cellular oncogenes in human head and neck solid tumours. Anticancer Res. 1985 Mar-Apr;5(2):221–224. [PubMed] [Google Scholar]
  24. Spandidos D. A., Wilkie N. M. Malignant transformation of early passage rodent cells by a single mutated human oncogene. Nature. 1984 Aug 9;310(5977):469–475. doi: 10.1038/310469a0. [DOI] [PubMed] [Google Scholar]
  25. Sweet R. W., Yokoyama S., Kamata T., Feramisco J. R., Rosenberg M., Gross M. The product of ras is a GTPase and the T24 oncogenic mutant is deficient in this activity. Nature. 1984 Sep 20;311(5983):273–275. doi: 10.1038/311273a0. [DOI] [PubMed] [Google Scholar]
  26. Thor A., Horan Hand P., Wunderlich D., Caruso A., Muraro R., Schlom J. Monoclonal antibodies define differential ras gene expression in malignant and benign colonic diseases. Nature. 1984 Oct 11;311(5986):562–565. doi: 10.1038/311562a0. [DOI] [PubMed] [Google Scholar]
  27. Varmus H. E. The molecular genetics of cellular oncogenes. Annu Rev Genet. 1984;18:553–612. doi: 10.1146/annurev.ge.18.120184.003005. [DOI] [PubMed] [Google Scholar]
  28. Willingham M. C., Pastan I., Shih T. Y., Scolnick E. M. Localization of the src gene product of the Harvey strain of MSV to plasma membrane of transformed cells by electron microscopic immunocytochemistry. Cell. 1980 Apr;19(4):1005–1014. doi: 10.1016/0092-8674(80)90091-4. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES