Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1987 May;7(5):2019–2023. doi: 10.1128/mcb.7.5.2019

Amplification of the neu (c-erbB-2) oncogene in human mammmary tumors is relatively frequent and is often accompanied by amplification of the linked c-erbA oncogene.

M van de Vijver, R van de Bersselaar, P Devilee, C Cornelisse, J Peterse, R Nusse
PMCID: PMC365313  PMID: 3299059

Abstract

We investigated alterations in the structure and expression of oncogenes in mammary tumors and mammary tumor-derived cell lines. In 16 of 95 samples, we detected amplification of the human neu oncogene, also known as c-erB-2, accompanied by overexpression in the tumors from which intact RNA could be isolated. In 10 of these DNAs, the linked oncogene c-erbA was also amplified, whereas another gene on human chromosome 17, p53, was present in normal copy numbers. Overexpression of c-erbA could not be detected in the tumors analyzed. The relatively high frequency of neu amplification points to a functional role in human breast cancer. Coamplification of the c-erbA oncogene could contribute to this disease as well but is most likely fortuitous.

Full text

PDF
2019

Images in this article

2020Image
on p.2020
2021Image
on p.2021

Selected References

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

  1. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  2. Baas F., Bikker H., Geurts van Kessel A., Melsert R., Pearson P. L., de Vijlder J. J., van Ommen G. J. The human thyroglobulin gene: a polymorphic marker localized distal to C-MYC on chromosome 8 band q24. Hum Genet. 1985;69(2):138–143. doi: 10.1007/BF00293284. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  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. Dayton A. I., Selden J. R., Laws G., Dorney D. J., Finan J., Tripputi P., Emanuel B. S., Rovera G., Nowell P. C., Croce C. M. A human c-erbA oncogene homologue is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4495–4499. doi: 10.1073/pnas.81.14.4495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Escot C., Theillet C., Lidereau R., Spyratos F., Champeme M. H., Gest J., Callahan R. Genetic alteration of the c-myc protooncogene (MYC) in human primary breast carcinomas. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4834–4838. doi: 10.1073/pnas.83.13.4834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fasano O., Birnbaum D., Edlund L., Fogh J., Wigler M. New human transforming genes detected by a tumorigenicity assay. Mol Cell Biol. 1984 Sep;4(9):1695–1705. doi: 10.1128/mcb.4.9.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Filmus J., Pollak M. N., Cailleau R., Buick R. N. MDA-468, a human breast cancer cell line with a high number of epidermal growth factor (EGF) receptors, has an amplified EGF receptor gene and is growth inhibited by EGF. Biochem Biophys Res Commun. 1985 Apr 30;128(2):898–905. doi: 10.1016/0006-291x(85)90131-7. [DOI] [PubMed] [Google Scholar]
  10. Frykberg L., Palmieri S., Beug H., Graf T., Hayman M. J., Vennström B. Transforming capacities of avian erythroblastosis virus mutants deleted in the erbA or erbB oncogenes. Cell. 1983 Jan;32(1):227–238. doi: 10.1016/0092-8674(83)90513-5. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Green S., Walter P., Kumar V., Krust A., Bornert J. M., Argos P., Chambon P. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986 Mar 13;320(6058):134–139. doi: 10.1038/320134a0. [DOI] [PubMed] [Google Scholar]
  13. Greene G. L., Gilna P., Waterfield M., Baker A., Hort Y., Shine J. Sequence and expression of human estrogen receptor complementary DNA. Science. 1986 Mar 7;231(4742):1150–1154. doi: 10.1126/science.3753802. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Isobe M., Emanuel B. S., Givol D., Oren M., Croce C. M. Localization of gene for human p53 tumour antigen to band 17p13. Nature. 1986 Mar 6;320(6057):84–85. doi: 10.1038/320084a0. [DOI] [PubMed] [Google Scholar]
  16. Jansson M., Philipson L., Vennström B. Isolation and characterization of multiple human genes homologous to the oncogenes of avian erythroblastosis virus. EMBO J. 1983;2(4):561–565. doi: 10.1002/j.1460-2075.1983.tb01463.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. King C. R., Kraus M. H., Williams L. T., Merlino G. T., Pastan I. H., Aaronson S. A. Human tumor cell lines with EGF receptor gene amplification in the absence of aberrant sized mRNAs. Nucleic Acids Res. 1985 Dec 9;13(23):8477–8486. doi: 10.1093/nar/13.23.8477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kozbor D., Croce C. M. Amplification of the c-myc oncogene in one of five human breast carcinoma cell lines. Cancer Res. 1984 Feb;44(2):438–441. [PubMed] [Google Scholar]
  20. Mathieu-Mahul D., Xu D. Q., Saule S., Lidereau R., Galibert F., Berger R., Mauchauffé M., Larsen C. J. An EcoRI restriction fragment length polymorphism (RFLP) in the human c-erb A locus. Hum Genet. 1985;71(1):41–44. doi: 10.1007/BF00295666. [DOI] [PubMed] [Google Scholar]
  21. Miller C., Mohandas T., Wolf D., Prokocimer M., Rotter V., Koeffler H. P. Human p53 gene localized to short arm of chromosome 17. 1986 Feb 27-Mar 5Nature. 319(6056):783–784. doi: 10.1038/319783a0. [DOI] [PubMed] [Google Scholar]
  22. Nau M. M., Brooks B. J., Jr, Carney D. N., Gazdar A. F., Battey J. F., Sausville E. A., Minna J. D. Human small-cell lung cancers show amplification and expression of the N-myc gene. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1092–1096. doi: 10.1073/pnas.83.4.1092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sap J., Muñoz A., Damm K., Goldberg Y., Ghysdael J., Leutz A., Beug H., Vennström B. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986 Dec 18;324(6098):635–640. doi: 10.1038/324635a0. [DOI] [PubMed] [Google Scholar]
  24. Schechter A. L., Hung M. C., Vaidyanathan L., Weinberg R. A., Yang-Feng T. L., Francke U., Ullrich A., Coussens L. The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science. 1985 Sep 6;229(4717):976–978. doi: 10.1126/science.2992090. [DOI] [PubMed] [Google Scholar]
  25. Sealy L., Moscovici G., Moscovici C., Bishop J. M. Site-specific mutagenesis of avian erythroblastosis virus: v-erb-A is not required for transformation of fibroblasts. Virology. 1983 Oct 15;130(1):179–194. doi: 10.1016/0042-6822(83)90126-5. [DOI] [PubMed] [Google Scholar]
  26. Sealy L., Privalsky M. L., Moscovici G., Moscovici C., Bishop J. M. Site-specific mutagenesis of avian erythroblastosis virus: erb-B is required for oncogenicity. Virology. 1983 Oct 15;130(1):155–178. doi: 10.1016/0042-6822(83)90125-3. [DOI] [PubMed] [Google Scholar]
  27. Seeger R. C., Brodeur G. M., Sather H., Dalton A., Siegel S. E., Wong K. Y., Hammond D. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med. 1985 Oct 31;313(18):1111–1116. doi: 10.1056/NEJM198510313131802. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. Spurr N. K., Solomon E., Jansson M., Sheer D., Goodfellow P. N., Bodmer W. F., Vennstrom B. Chromosomal localisation of the human homologues to the oncogenes erbA and B. EMBO J. 1984 Jan;3(1):159–163. doi: 10.1002/j.1460-2075.1984.tb01777.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Van der Bliek A. M., Van der Velde-Koerts T., Ling V., Borst P. Overexpression and amplification of five genes in a multidrug-resistant Chinese hamster ovary cell line. Mol Cell Biol. 1986 May;6(5):1671–1678. doi: 10.1128/mcb.6.5.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vennström B., Bishop J. M. Isolation and characterization of chicken DNA homologous to the two putative oncogenes of avian erythroblastosis virus. Cell. 1982 Jan;28(1):135–143. doi: 10.1016/0092-8674(82)90383-x. [DOI] [PubMed] [Google Scholar]
  33. Weinberger C., Hollenberg S. M., Rosenfeld M. G., Evans R. M. Domain structure of human glucocorticoid receptor and its relationship to the v-erb-A oncogene product. Nature. 1985 Dec 19;318(6047):670–672. doi: 10.1038/318670a0. [DOI] [PubMed] [Google Scholar]
  34. Weinberger C., Thompson C. C., Ong E. S., Lebo R., Gruol D. J., Evans R. M. The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986 Dec 18;324(6098):641–646. doi: 10.1038/324641a0. [DOI] [PubMed] [Google Scholar]
  35. Wolf D., Harris N., Goldfinger N., Rotter V. Isolation of a full-length mouse cDNA clone coding for an immunologically distinct p53 molecule. Mol Cell Biol. 1985 Jan;5(1):127–132. doi: 10.1128/mcb.5.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wong A. J., Ruppert J. M., Eggleston J., Hamilton S. R., Baylin S. B., Vogelstein B. Gene amplification of c-myc and N-myc in small cell carcinoma of the lung. Science. 1986 Jul 25;233(4762):461–464. doi: 10.1126/science.3014659. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Yamamoto T., Kamata N., Kawano H., Shimizu S., Kuroki T., Toyoshima K., Rikimaru K., Nomura N., Ishizaki R., Pastan I. High incidence of amplification of the epidermal growth factor receptor gene in human squamous carcinoma cell lines. Cancer Res. 1986 Jan;46(1):414–416. [PubMed] [Google Scholar]
  39. Yokota J., Tsunetsugu-Yokota Y., Battifora H., Le Fevre C., Cline M. J. Alterations of myc, myb, and rasHa proto-oncogenes in cancers are frequent and show clinical correlation. Science. 1986 Jan 17;231(4735):261–265. doi: 10.1126/science.3941898. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. de Bruijn M. H., Van der Bliek A. M., Biedler J. L., Borst P. Differential amplification and disproportionate expression of five genes in three multidrug-resistant Chinese hamster lung cell lines. Mol Cell Biol. 1986 Dec;6(12):4717–4722. doi: 10.1128/mcb.6.12.4717. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES