Skip to main content
PMC 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
. 1987 May;84(10):3234–3238. doi: 10.1073/pnas.84.10.3234

Expression of p21ras in normal and malignant human tissues: lack of association with proliferation and malignancy.

P G Chesa, W J Rettig, M R Melamed, L J Old, H L Niman
PMCID: PMC304843  PMID: 3554234

Abstract

Proteins encoded by cellular ras oncogenes (p21ras) are expressed in a wide variety of malignant tumors, including carcinomas, lymphomas, and neuroectodermal tumors. The function of p21ras in these tumors and the distribution and role of p21ras in corresponding normal tissues are unclear. This immunohistochemical study examined the relationship between p21ras expression and malignant transformation, cellular differentiation, and proliferative activity in vivo. p21ras was found to be widely expressed in normal tissues, but within those tissues expression was often sharply restricted to cells at specific stages of differentiation; terminally differentiated cells generally showed stronger reactivity with antibodies to p21ras than did rapidly proliferating cells. Fetal and adult tissues had corresponding patterns of p21ras expression, and the distribution of p21ras in neoplasms paralleled the pattern in normal tissue from which they were derived. Thus, p21ras seems to play a role in many fully differentiated cell types, and levels of p21ras expression do not correlate with proliferative activity in normal cell or, in contrast to past reports, with the transformed phenotype.

Full text

PDF
3234

Images in this article

3235Image
on p.3235
3235Image
on p.3235
3236Image
on p.3236
3237Image
on p.3237

Selected References

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

  1. Albino A. P., Le Strange R., Oliff A. I., Furth M. E., Old L. J. Transforming ras genes from human melanoma: a manifestation of tumour heterogeneity? Nature. 1984 Mar 1;308(5954):69–72. doi: 10.1038/308069a0. [DOI] [PubMed] [Google Scholar]
  2. Bishop J. M. Viral oncogenes. Cell. 1985 Aug;42(1):23–38. doi: 10.1016/s0092-8674(85)80098-2. [DOI] [PubMed] [Google Scholar]
  3. Brugge J. S., Cotton P. C., Queral A. E., Barrett J. N., Nonner D., Keane R. W. Neurones express high levels of a structurally modified, activated form of pp60c-src. Nature. 1985 Aug 8;316(6028):554–557. doi: 10.1038/316554a0. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Chesa P. G., Rettig W. J., Melamed M. R. Expression of cytokeratins in normal and neoplastic colonic epithelial cells. Implications for cellular differentiation and carcinogenesis. Am J Surg Pathol. 1986 Dec;10(12):829–835. doi: 10.1097/00000478-198612000-00001. [DOI] [PubMed] [Google Scholar]
  6. 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]
  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. 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]
  10. 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]
  11. Hand P. H., Thor A., Wunderlich D., Muraro R., Caruso A., Schlom J. Monoclonal antibodies of predefined specificity detect activated ras gene expression in human mammary and colon carcinomas. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5227–5231. doi: 10.1073/pnas.81.16.5227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hayashi K., Kakizoe T., Sugimura T. In vivo amplification and rearrangement of the c-Ha-ras-1 sequence in a human bladder carcinoma. Gan. 1983 Dec;74(6):798–801. [PubMed] [Google Scholar]
  13. Kerr I. B., Lee F. D., Quintanilla M., Balmain A. Immunocytochemical demonstration of p21 ras family oncogene product in normal mucosa and in premalignant and malignant tumours of the colorectum. Br J Cancer. 1985 Nov;52(5):695–700. doi: 10.1038/bjc.1985.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Niman H. L. Human oncogene-related proteins in urine during pregnancy and neoplasia. Clin Lab Med. 1986 Mar;6(1):181–196. [PubMed] [Google Scholar]
  15. 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]
  16. Reddy E. P., Reynolds R. K., Santos E., Barbacid M. A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature. 1982 Nov 11;300(5888):149–152. doi: 10.1038/300149a0. [DOI] [PubMed] [Google Scholar]
  17. Santos E., Tronick S. R., Aaronson S. A., Pulciani S., Barbacid M. T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB- and Harvey-MSV transforming genes. Nature. 1982 Jul 22;298(5872):343–347. doi: 10.1038/298343a0. [DOI] [PubMed] [Google Scholar]
  18. Schwab M., Alitalo K., Varmus H. E., Bishop J. M., George D. A cellular oncogene (c-Ki-ras) is amplified, overexpressed, and located within karyotypic abnormalities in mouse adrenocortical tumour cells. Nature. 1983 Jun 9;303(5917):497–501. doi: 10.1038/303497a0. [DOI] [PubMed] [Google Scholar]
  19. Scolnick E. M., Weeks M. O., Shih T. Y., Ruscetti S. K., Dexter T. M. Markedly elevated levels of an endogenous sarc protein in a hemopoietic precursor cell line. Mol Cell Biol. 1981 Jan;1(1):66–74. doi: 10.1128/mcb.1.1.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Shimizu K., Goldfarb M., Suard Y., Perucho M., Li Y., Kamata T., Feramisco J., Stavnezer E., Fogh J., Wigler M. H. Three human transforming genes are related to the viral ras oncogenes. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2112–2116. doi: 10.1073/pnas.80.8.2112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Tabin C. J., Bradley S. M., Bargmann C. I., Weinberg R. A., Papageorge A. G., Scolnick E. M., Dhar R., Lowy D. R., Chang E. H. Mechanism of activation of a human oncogene. Nature. 1982 Nov 11;300(5888):143–149. doi: 10.1038/300143a0. [DOI] [PubMed] [Google Scholar]
  23. Tanaka T., Slamon D. J., Battifora H., Cline M. J. Expression of p21 ras oncoproteins in human cancers. Cancer Res. 1986 Mar;46(3):1465–1470. [PubMed] [Google Scholar]
  24. Taparowsky E., Suard Y., Fasano O., Shimizu K., Goldfarb M., Wigler M. Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature. 1982 Dec 23;300(5894):762–765. doi: 10.1038/300762a0. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Viola M. V., Fromowitz F., Oravez S., Deb S., Finkel G., Lundy J., Hand P., Thor A., Schlom J. Expression of ras oncogene p21 in prostate cancer. N Engl J Med. 1986 Jan 16;314(3):133–137. doi: 10.1056/NEJM198601163140301. [DOI] [PubMed] [Google Scholar]
  27. Viola M. V., Fromowitz F., Oravez S., Deb S., Schlom J. ras Oncogene p21 expression is increased in premalignant lesions and high grade bladder carcinoma. J Exp Med. 1985 May 1;161(5):1213–1218. doi: 10.1084/jem.161.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Williams A. R., Piris J., Spandidos D. A., Wyllie A. H. Immunohistochemical detection of the ras oncogene p21 product in an experimental tumour and in human colorectal neoplasms. Br J Cancer. 1985 Nov;52(5):687–693. doi: 10.1038/bjc.1985.244. [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