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
. 1987 Dec;84(23):8498–8501. doi: 10.1073/pnas.84.23.8498

Stage- and tissue-specific expression of the neu oncogene in rat development.

Y Kokai 1, J A Cohen 1, J A Drebin 1, M I Greene 1
PMCID: PMC299571  PMID: 3317411

Abstract

The neu oncogene (also referred to as c-erbB-2 and HER2) encodes a 185-kDa transmembrane glycoprotein with tyrosine kinase activity termed p185. The p185 glycoprotein is structurally related to the epidermal growth factor receptor. It is thought that p185 is the receptor for an as yet unidentified growth factor. In the present study, RNA blot analyses and immunohistochemical studies were performed on rat tissues obtained from a variety of prenatal and postnatal stages to examine the expression of the neu oncogene and its product, p185, during normal development. Expression of the neu gene was detected in mid-gestation embryos in a variety of tissues including nervous system, connective tissue, and secretory epithelium, but not in lymphoid tissue. In adult animals, secretory epithelial tissues and basal cells of the skin expressed neu. These studies demonstrate that the neu gene is expressed in a tissue- and developmental stage-specific manner. We suggest that the p185 molecule plays an important role in the growth and development of a variety of tissues, and, in particular, in epithelial tissue.

Full text

PDF
8498

Images in this article

8499Image
on p.8499
8499Image
on p.8499
8500Image
on p.8500
8500Image
on p.8500
8500Image
on p.8500
8500Image
on p.8500

Selected References

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

  1. Akiyama T., Sudo C., Ogawara H., Toyoshima K., Yamamoto T. The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science. 1986 Jun 27;232(4758):1644–1646. doi: 10.1126/science.3012781. [DOI] [PubMed] [Google Scholar]
  2. Bargmann C. I., Hung M. C., Weinberg R. A. Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185. Cell. 1986 Jun 6;45(5):649–657. doi: 10.1016/0092-8674(86)90779-8. [DOI] [PubMed] [Google Scholar]
  3. Bargmann C. I., Hung M. C., Weinberg R. A. The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature. 1986 Jan 16;319(6050):226–230. doi: 10.1038/319226a0. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Coussens L., Yang-Feng T. L., Liao Y. C., Chen E., Gray A., McGrath J., Seeburg P. H., Libermann T. A., Schlessinger J., Francke U. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science. 1985 Dec 6;230(4730):1132–1139. doi: 10.1126/science.2999974. [DOI] [PubMed] [Google Scholar]
  6. Drebin J. A., Link V. C., Stern D. F., Weinberg R. A., Greene M. I. Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell. 1985 Jul;41(3):697–706. doi: 10.1016/s0092-8674(85)80050-7. [DOI] [PubMed] [Google Scholar]
  7. Drebin J. A., Stern D. F., Link V. C., Weinberg R. A., Greene M. I. Monoclonal antibodies identify a cell-surface antigen associated with an activated cellular oncogene. Nature. 1984 Dec 6;312(5994):545–548. doi: 10.1038/312545a0. [DOI] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  9. Fukushige S., Matsubara K., Yoshida M., Sasaki M., Suzuki T., Semba K., Toyoshima K., Yamamoto T. Localization of a novel v-erbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line. Mol Cell Biol. 1986 Mar;6(3):955–958. doi: 10.1128/mcb.6.3.955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  11. Hung M. C., Schechter A. L., Chevray P. Y., Stern D. F., Weinberg R. A. Molecular cloning of the neu gene: absence of gross structural alteration in oncogenic alleles. Proc Natl Acad Sci U S A. 1986 Jan;83(2):261–264. doi: 10.1073/pnas.83.2.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jakobovits A., Shackleford G. M., Varmus H. E., Martin G. R. Two proto-oncogenes implicated in mammary carcinogenesis, int-1 and int-2, are independently regulated during mouse development. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7806–7810. doi: 10.1073/pnas.83.20.7806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. King C. R., Kraus M. H., Aaronson S. A. Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science. 1985 Sep 6;229(4717):974–976. doi: 10.1126/science.2992089. [DOI] [PubMed] [Google Scholar]
  14. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  15. Müller R., Slamon D. J., Tremblay J. M., Cline M. J., Verma I. M. Differential expression of cellular oncogenes during pre- and postnatal development of the mouse. Nature. 1982 Oct 14;299(5884):640–644. doi: 10.1038/299640a0. [DOI] [PubMed] [Google Scholar]
  16. Müller R., Tremblay J. M., Adamson E. D., Verma I. M. Tissue and cell type-specific expression of two human c-onc genes. Nature. 1983 Aug 4;304(5925):454–456. doi: 10.1038/304454a0. [DOI] [PubMed] [Google Scholar]
  17. Neckameyer W. S., Shibuya M., Hsu M. T., Wang L. H. Proto-oncogene c-ros codes for a molecule with structural features common to those of growth factor receptors and displays tissue specific and developmentally regulated expression. Mol Cell Biol. 1986 May;6(5):1478–1486. doi: 10.1128/mcb.6.5.1478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ozanne B., Richards C. S., Hendler F., Burns D., Gusterson B. Over-expression of the EGF receptor is a hallmark of squamous cell carcinomas. J Pathol. 1986 May;149(1):9–14. doi: 10.1002/path.1711490104. [DOI] [PubMed] [Google Scholar]
  19. Schechter A. L., Stern D. F., Vaidyanathan L., Decker S. J., Drebin J. A., Greene M. I., Weinberg R. A. The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature. 1984 Dec 6;312(5994):513–516. doi: 10.1038/312513a0. [DOI] [PubMed] [Google Scholar]
  20. Semba K., Kamata N., Toyoshima K., Yamamoto T. A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6497–6501. doi: 10.1073/pnas.82.19.6497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Slamon D. J., Clark G. M., Wong S. G., Levin W. J., Ullrich A., McGuire W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. doi: 10.1126/science.3798106. [DOI] [PubMed] [Google Scholar]
  22. Sorge L. K., Levy B. T., Maness P. F. pp60c-src is developmentally regulated in the neural retina. Cell. 1984 Feb;36(2):249–257. doi: 10.1016/0092-8674(84)90218-6. [DOI] [PubMed] [Google Scholar]
  23. Spiegelman B. M., Frank M., Green H. Molecular cloning of mRNA from 3T3 adipocytes. Regulation of mRNA content for glycerophosphate dehydrogenase and other differentiation-dependent proteins during adipocyte development. J Biol Chem. 1983 Aug 25;258(16):10083–10089. [PubMed] [Google Scholar]
  24. Stern D. F., Heffernan P. A., Weinberg R. A. p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity. Mol Cell Biol. 1986 May;6(5):1729–1740. doi: 10.1128/mcb.6.5.1729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Thiery J. P., Duband J. L., Delouvée A. Pathways and mechanisms of avian trunk neural crest cell migration and localization. Dev Biol. 1982 Oct;93(2):324–343. doi: 10.1016/0012-1606(82)90121-x. [DOI] [PubMed] [Google Scholar]
  26. Trojanowski J. Q., Obrocka M. A., Lee V. M. A comparison of eight different chromogen protocols for the demonstration of immunoreactive neurofilaments or glial filaments in rat cerebellum using the peroxidase-antiperoxidase method and monoclonal antibodies. J Histochem Cytochem. 1983 Oct;31(10):1217–1223. doi: 10.1177/31.10.6350434. [DOI] [PubMed] [Google Scholar]
  27. Williams A. F., Galfrè G., Milstein C. Analysis of cell surfaces by xenogeneic myeloma-hybrid antibodies: differentiation antigens of rat lymphocytes. Cell. 1977 Nov;12(3):663–673. doi: 10.1016/0092-8674(77)90266-5. [DOI] [PubMed] [Google Scholar]
  28. Yamamoto T., Ikawa S., Akiyama T., Semba K., Nomura N., Miyajima N., Saito T., Toyoshima K. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature. 1986 Jan 16;319(6050):230–234. doi: 10.1038/319230a0. [DOI] [PubMed] [Google Scholar]
  29. Yokota J., Yamamoto T., Toyoshima K., Terada M., Sugimura T., Battifora H., Cline M. J. Amplification of c-erbB-2 oncogene in human adenocarcinomas in vivo. Lancet. 1986 Apr 5;1(8484):765–767. doi: 10.1016/s0140-6736(86)91782-4. [DOI] [PubMed] [Google Scholar]
  30. Zimmerman K. A., Yancopoulos G. D., Collum R. G., Smith R. K., Kohl N. E., Denis K. A., Nau M. M., Witte O. N., Toran-Allerand D., Gee C. E. Differential expression of myc family genes during murine development. 1986 Feb 27-Mar 5Nature. 319(6056):780–783. doi: 10.1038/319780a0. [DOI] [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