Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1990 Jun;10(6):3247–3252. doi: 10.1128/mcb.10.6.3247

Transformation of NIH 3T3 cells by overexpression of the normal coding sequence of the rat neu gene.

E Di Marco 1, J H Pierce 1, C L Knicley 1, P P Di Fiore 1
PMCID: PMC360691  PMID: 1971420

Abstract

While the normal human erbB-2 gene is potently transforming when overexpressed in NIH 3T3 cells, its rat homolog, the neu gene, seems to acquire transforming properties only upon alteration of its coding sequence. In this study, we compared the effects of different levels of expression of normal erbB-2 and neu in NIH 3T3 cells. Our results revealed that the normal rat neu gene acts as a potent oncogene when sufficiently overexpressed in NIH 3T3 cells.

Full text

PDF
3247

Images in this article

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., Weinberg R. A. Increased tyrosine kinase activity associated with the protein encoded by the activated neu oncogene. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5394–5398. doi: 10.1073/pnas.85.15.5394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bargmann C. I., Weinberg R. A. Oncogenic activation of the neu-encoded receptor protein by point mutation and deletion. EMBO J. 1988 Jul;7(7):2043–2052. doi: 10.1002/j.1460-2075.1988.tb03044.x. [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. Di Fiore P. P., Pierce J. H., Kraus M. H., Segatto O., King C. R., Aaronson S. A. erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science. 1987 Jul 10;237(4811):178–182. doi: 10.1126/science.2885917. [DOI] [PubMed] [Google Scholar]
  7. Di Fiore P. P., Segatto O., Lonardo F., Fazioli F., Pierce J. H., Aaronson S. A. The carboxy-terminal domains of erbB-2 and epidermal growth factor receptor exert different regulatory effects on intrinsic receptor tyrosine kinase function and transforming activity. Mol Cell Biol. 1990 Jun;10(6):2749–2756. doi: 10.1128/mcb.10.6.2749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  10. Hudziak R. M., Schlessinger J., Ullrich A. Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7159–7163. doi: 10.1073/pnas.84.20.7159. [DOI] [PMC free article] [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. 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]
  13. Kraus M. H., Popescu N. C., Amsbaugh S. C., King C. R. Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms. EMBO J. 1987 Mar;6(3):605–610. doi: 10.1002/j.1460-2075.1987.tb04797.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mulligan R. C., Berg P. Selection for animal cells that express the Escherichia coli gene coding for xanthine-guanine phosphoribosyltransferase. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2072–2076. doi: 10.1073/pnas.78.4.2072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Padhy L. C., Shih C., Cowing D., Finkelstein R., Weinberg R. A. Identification of a phosphoprotein specifically induced by the transforming DNA of rat neuroblastomas. Cell. 1982 Apr;28(4):865–871. doi: 10.1016/0092-8674(82)90065-4. [DOI] [PubMed] [Google Scholar]
  16. Pang D. T., Sharma B. R., Shafer J. A. Purification of the catalytically active phosphorylated form of insulin receptor kinase by affinity chromatography with O-phosphotyrosyl-binding antibodies. Arch Biochem Biophys. 1985 Oct;242(1):176–186. doi: 10.1016/0003-9861(85)90491-6. [DOI] [PubMed] [Google Scholar]
  17. Segatto O., King C. R., Pierce J. H., Di Fiore P. P., Aaronson S. A. Different structural alterations upregulate in vitro tyrosine kinase activity and transforming potency of the erbB-2 gene. Mol Cell Biol. 1988 Dec;8(12):5570–5574. doi: 10.1128/mcb.8.12.5570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Shih C., Padhy L. C., Murray M., Weinberg R. A. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature. 1981 Mar 19;290(5803):261–264. doi: 10.1038/290261a0. [DOI] [PubMed] [Google Scholar]
  20. Shinnick T. M., Lerner R. A., Sutcliffe J. G. Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981 Oct 15;293(5833):543–548. doi: 10.1038/293543a0. [DOI] [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. Slamon D. J., Godolphin W., Jones L. A., Holt J. A., Wong S. G., Keith D. E., Levin W. J., Stuart S. G., Udove J., Ullrich A. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989 May 12;244(4905):707–712. doi: 10.1126/science.2470152. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Stern D. F., Kamps M. P., Cao H. Oncogenic activation of p185neu stimulates tyrosine phosphorylation in vivo. Mol Cell Biol. 1988 Sep;8(9):3969–3973. doi: 10.1128/mcb.8.9.3969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wigler M., Silverstein S., Lee L. S., Pellicer A., Cheng Y. c., Axel R. Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells. Cell. 1977 May;11(1):223–232. doi: 10.1016/0092-8674(77)90333-6. [DOI] [PubMed] [Google Scholar]
  26. Yarden Y., Weinberg R. A. Experimental approaches to hypothetical hormones: detection of a candidate ligand of the neu protooncogene. Proc Natl Acad Sci U S A. 1989 May;86(9):3179–3183. doi: 10.1073/pnas.86.9.3179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES