• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. May 1987; 7(5): 2019–2023.
PMCID: PMC365313

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.


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

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • 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. [PubMed]
  • Baas F, Bikker H, Geurts van Kessel A, Melsert R, Pearson PL, de Vijlder JJ, van Ommen GJ. The human thyroglobulin gene: a polymorphic marker localized distal to C-MYC on chromosome 8 band q24. Hum Genet. 1985;69(2):138–143. [PubMed]
  • Bargmann CI, Hung MC, Weinberg RA. 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. [PubMed]
  • Bargmann CI, Hung MC, Weinberg RA. The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature. 1986 Jan 16;319(6050):226–230. [PubMed]
  • Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U, et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science. 1985 Dec 6;230(4730):1132–1139. [PubMed]
  • Dayton AI, Selden JR, Laws G, Dorney DJ, Finan J, Tripputi P, Emanuel BS, Rovera G, Nowell PC, Croce CM. 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. [PMC free article] [PubMed]
  • de Bruijn MH, Van der Bliek AM, Biedler JL, 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. [PMC free article] [PubMed]
  • Escot C, Theillet C, Lidereau R, Spyratos F, Champeme MH, 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Filmus J, Pollak MN, Cailleau R, Buick RN. 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. [PubMed]
  • Frykberg L, Palmieri S, Beug H, Graf T, Hayman MJ, Vennström B. Transforming capacities of avian erythroblastosis virus mutants deleted in the erbA or erbB oncogenes. Cell. 1983 Jan;32(1):227–238. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986 Mar 13;320(6058):134–139. [PubMed]
  • Greene GL, 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. [PubMed]
  • Hung MC, Schechter AL, Chevray PY, Stern DF, Weinberg RA. 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. [PMC free article] [PubMed]
  • Isobe M, Emanuel BS, Givol D, Oren M, Croce CM. Localization of gene for human p53 tumour antigen to band 17p13. Nature. 1986 Mar 6;320(6057):84–85. [PubMed]
  • 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. [PMC free article] [PubMed]
  • King CR, Kraus MH, Aaronson SA. Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science. 1985 Sep 6;229(4717):974–976. [PubMed]
  • King CR, Kraus MH, Williams LT, Merlino GT, Pastan IH, Aaronson SA. 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. [PMC free article] [PubMed]
  • Kozbor D, Croce CM. Amplification of the c-myc oncogene in one of five human breast carcinoma cell lines. Cancer Res. 1984 Feb;44(2):438–441. [PubMed]
  • Mathieu-Mahul D, Xu DQ, Saule S, Lidereau R, Galibert F, Berger R, Mauchauffé M, Larsen CJ. An EcoRI restriction fragment length polymorphism (RFLP) in the human c-erb A locus. Hum Genet. 1985;71(1):41–44. [PubMed]
  • Miller C, Mohandas T, Wolf D, Prokocimer M, Rotter V, Koeffler HP. Human p53 gene localized to short arm of chromosome 17. Nature. 319(6056):783–784. [PubMed]
  • Nau MM, Brooks BJ, Jr, Carney DN, Gazdar AF, Battey JF, Sausville EA, Minna JD. 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Schechter AL, Hung MC, Vaidyanathan L, Weinberg RA, Yang-Feng TL, 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. [PubMed]
  • Sealy L, Moscovici G, Moscovici C, Bishop JM. 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. [PubMed]
  • Sealy L, Privalsky ML, Moscovici G, Moscovici C, Bishop JM. Site-specific mutagenesis of avian erythroblastosis virus: erb-B is required for oncogenicity. Virology. 1983 Oct 15;130(1):155–178. [PubMed]
  • Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, Wong KY, 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. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. [PubMed]
  • Spurr NK, Solomon E, Jansson M, Sheer D, Goodfellow PN, Bodmer WF, Vennstrom B. Chromosomal localisation of the human homologues to the oncogenes erbA and B. EMBO J. 1984 Jan;3(1):159–163. [PMC free article] [PubMed]
  • Van der Bliek AM, 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. [PMC free article] [PubMed]
  • Vennström B, Bishop JM. Isolation and characterization of chicken DNA homologous to the two putative oncogenes of avian erythroblastosis virus. Cell. 1982 Jan;28(1):135–143. [PubMed]
  • Weinberger C, Hollenberg SM, Rosenfeld MG, Evans RM. Domain structure of human glucocorticoid receptor and its relationship to the v-erb-A oncogene product. Nature. 1985 Dec 19;318(6047):670–672. [PubMed]
  • Weinberger C, Thompson CC, Ong ES, Lebo R, Gruol DJ, Evans RM. The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986 Dec 18;324(6098):641–646. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Wong AJ, Ruppert JM, Eggleston J, Hamilton SR, Baylin SB, 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. [PubMed]
  • 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. [PubMed]
  • Yamamoto T, Kamata N, Kawano H, Shimizu S, Kuroki T, Toyoshima K, Rikimaru K, Nomura N, Ishizaki R, Pastan I, et al. 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]
  • Yokota J, Yamamoto T, Toyoshima K, Terada M, Sugimura T, Battifora H, Cline MJ. Amplification of c-erbB-2 oncogene in human adenocarcinomas in vivo. Lancet. 1986 Apr 5;1(8484):765–767. [PubMed]
  • Yokota J, Tsunetsugu-Yokota Y, Battifora H, Le Fevre C, Cline MJ. Alterations of myc, myb, and rasHa proto-oncogenes in cancers are frequent and show clinical correlation. Science. 1986 Jan 17;231(4735):261–265. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...