Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1988 Apr;57(4):358–363. doi: 10.1038/bjc.1988.82

Expression of oncogenes in thyroid tumours: coexpression of c-erbB2/neu and c-erbB.

R Aasland 1, J R Lillehaug 1, R Male 1, O Jøsendal 1, J E Varhaug 1, K Kleppe 1
PMCID: PMC2246566  PMID: 3390372

Abstract

The receptor-type oncogenes c-erbB2/neu and c-erbB have been found amplified and/or overexpressed in a number of tumours of epithelial origin. We have studied the expression of oncogenes in biopsies from human thyroid tumours. The c-erbB2/neu and c-erbB oncogenes showed two- to three-fold higher levels of RNA in papillary carcinomas and lymph node metastases as well as in one adenoma when compared to non-tumour tissue. The nuclear oncogenes c-myc and c-fos were found to be expressed at varying levels in both non-tumour and tumour tissue. RNA transcripts specific for the platelet-derived growth factor A and B chains and the N-ras oncogene were detected in one anaplastic carcinoma. Neither rearrangements nor amplifications of oncogenes were observed in the thyroid tumours. These data are particularly interesting in light of the recent findings that epidermal growth factor induces proliferation and dedifferentiation of normal thyroid epithelial cells in vitro. We suggest that the epidermal growth factor or other ligands for the c-erbB and c-erbB2/neu receptors may contribute to the development and/or maintenance of the malignant phenotype of papillary carcinomas of the thyroid.

Full text

PDF
358

Images in this article

360Figure 1
on p.360
360Figure 2
on p.360
360Figure 3
on p.360
362Figure 5
on p.362
362Figure 6
on p.362

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. 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]
  3. Barnes D. W. Epidermal growth factor inhibits growth of A431 human epidermoid carcinoma in serum-free cell culture. J Cell Biol. 1982 Apr;93(1):1–4. doi: 10.1083/jcb.93.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Betsholtz C., Johnsson A., Heldin C. H., Westermark B., Lind P., Urdea M. S., Eddy R., Shows T. B., Philpott K., Mellor A. L. cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines. Nature. 1986 Apr 24;320(6064):695–699. doi: 10.1038/320695a0. [DOI] [PubMed] [Google Scholar]
  5. Brocas H., Christophe D., Pohl V., Vassart G. Cloning of human thyroglobulin complementary DNA. FEBS Lett. 1982 Jan 25;137(2):189–192. doi: 10.1016/0014-5793(82)80346-3. [DOI] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Colletta G., Cirafici A. M., Vecchio G. Induction of the c-fos oncogene by thyrotropic hormone in rat thyroid cells in culture. Science. 1986 Jul 25;233(4762):458–460. doi: 10.1126/science.3726540. [DOI] [PubMed] [Google Scholar]
  8. Curran T., MacConnell W. P., van Straaten F., Verma I. M. Structure of the FBJ murine osteosarcoma virus genome: molecular cloning of its associated helper virus and the cellular homolog of the v-fos gene from mouse and human cells. Mol Cell Biol. 1983 May;3(5):914–921. doi: 10.1128/mcb.3.5.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dere W. H., Hirayu H., Rapoport B. TSH and cAMP enhance expression of the myc proto-oncogene in cultured thyroid cells. Endocrinology. 1985 Nov;117(5):2249–2251. doi: 10.1210/endo-117-5-2249. [DOI] [PubMed] [Google Scholar]
  10. Dickson R. B., Kasid A., Huff K. K., Bates S. E., Knabbe C., Bronzert D., Gelmann E. P., Lippman M. E. Activation of growth factor secretion in tumorigenic states of breast cancer induced by 17 beta-estradiol or v-Ha-ras oncogene. Proc Natl Acad Sci U S A. 1987 Feb;84(3):837–841. doi: 10.1073/pnas.84.3.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9;307(5951):521–527. doi: 10.1038/307521a0. [DOI] [PubMed] [Google Scholar]
  12. Eggo M. C., Bachrach L. K., Fayet G., Errick J., Kudlow J. E., Cohen M. F., Burrow G. N. The effects of growth factors and serum on DNA synthesis and differentiation in thyroid cells in culture. Mol Cell Endocrinol. 1984 Dec;38(2-3):141–150. doi: 10.1016/0303-7207(84)90112-6. [DOI] [PubMed] [Google Scholar]
  13. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Fusco A., Grieco M., Santoro M., Berlingieri M. T., Pilotti S., Pierotti M. A., Della Porta G., Vecchio G. A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases. Nature. 1987 Jul 9;328(6126):170–172. doi: 10.1038/328170a0. [DOI] [PubMed] [Google Scholar]
  16. Gazin C., Dupont de Dinechin S., Hampe A., Masson J. M., Martin P., Stehelin D., Galibert F. Nucleotide sequence of the human c-myc locus: provocative open reading frame within the first exon. EMBO J. 1984 Feb;3(2):383–387. doi: 10.1002/j.1460-2075.1984.tb01816.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gill G. N., Lazar C. S. Increased phosphotyrosine content and inhibition of proliferation in EGF-treated A431 cells. Nature. 1981 Sep 24;293(5830):305–307. doi: 10.1038/293305a0. [DOI] [PubMed] [Google Scholar]
  18. Humphries H., Mac Neil S., Munro D. S., Tomlinson S. Interaction of epidermal growth factor with receptors on human and porcine thyroid membranes. J Endocrinol. 1984 Jul;102(1):57–61. doi: 10.1677/joe.0.1020057. [DOI] [PubMed] [Google Scholar]
  19. Kadowaki T., Kasuga M., Tobe K., Takaku F., Nishida E., Sakai H., Koyasu S., Yahara I., Toyoshima K., Yamamoto T. A Mr = 190,000 glycoprotein phosphorylated on tyrosine residues in epidermal growth factor stimulated KB cells is the product of the c-erbB-2 gene. Biochem Biophys Res Commun. 1987 Apr 29;144(2):699–704. doi: 10.1016/s0006-291x(87)80021-9. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  23. Lee L. S., Weinstein I. B. Epidermal growth factor, like phorbol esters, induces plasminogen activator in HeLa cells. Nature. 1978 Aug 17;274(5672):696–697. doi: 10.1038/274696a0. [DOI] [PubMed] [Google Scholar]
  24. Libermann T. A., Nusbaum H. R., Razon N., Kris R., Lax I., Soreq H., Whittle N., Waterfield M. D., Ullrich A., Schlessinger J. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985 Jan 10;313(5998):144–147. doi: 10.1038/313144a0. [DOI] [PubMed] [Google Scholar]
  25. Murnane J. P. Inducible gene expression by DNA rearrangements in human cells. Mol Cell Biol. 1986 Feb;6(2):549–558. doi: 10.1128/mcb.6.2.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  27. Robbins K. C., Devare S. G., Aaronson S. A. Molecular cloning of integrated simian sarcoma virus: genome organization of infectious DNA clones. Proc Natl Acad Sci U S A. 1981 May;78(5):2918–2922. doi: 10.1073/pnas.78.5.2918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Roger P. P., Dumont J. E. Factors controlling proliferation and differentiation of canine thyroid cells cultured in reduced serum conditions: effects of thyrotropin, cyclic AMP and growth factors. Mol Cell Endocrinol. 1984 Jun;36(1-2):79–93. doi: 10.1016/0303-7207(84)90087-x. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. Slamon D. J., deKernion J. B., Verma I. M., Cline M. J. Expression of cellular oncogenes in human malignancies. Science. 1984 Apr 20;224(4646):256–262. doi: 10.1126/science.6538699. [DOI] [PubMed] [Google Scholar]
  32. Stoppelli M. P., Verde P., Grimaldi G., Locatelli E. K., Blasi F. Increase in urokinase plasminogen activator mRNA synthesis in human carcinoma cells is a primary effect of the potent tumor promoter, phorbol myristate acetate. J Cell Biol. 1986 Apr;102(4):1235–1241. doi: 10.1083/jcb.102.4.1235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Taparowsky E., Shimizu K., Goldfarb M., Wigler M. Structure and activation of the human N-ras gene. Cell. 1983 Sep;34(2):581–586. doi: 10.1016/0092-8674(83)90390-2. [DOI] [PubMed] [Google Scholar]
  34. Todaro G. J., Fryling C., De Larco J. E. Transforming growth factors produced by certain human tumor cells: polypeptides that interact with epidermal growth factor receptors. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5258–5262. doi: 10.1073/pnas.77.9.5258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tramontano D., Chin W. W., Moses A. C., Ingbar S. H. Thyrotropin and dibutyryl cyclic AMP increase levels of c-myc and c-fos mRNAs in cultured rat thyroid cells. J Biol Chem. 1986 Mar 25;261(9):3919–3922. [PubMed] [Google Scholar]
  36. Waters M. J., Tweedale R. C., Whip T. A., Shaw G., Manley S. W., Bourke J. R. Dedifferentiation of cultured thyroid cells by epidermal growth factor: some insights into the mechanism. Mol Cell Endocrinol. 1987 Feb;49(2-3):109–117. doi: 10.1016/0303-7207(87)90204-8. [DOI] [PubMed] [Google Scholar]
  37. Westermark K., Karlsson F. A., Westermark B. Epidermal growth factor modulates thyroid growth and function in culture. Endocrinology. 1983 May;112(5):1680–1686. doi: 10.1210/endo-112-5-1680. [DOI] [PubMed] [Google Scholar]
  38. Xu Y. H., Ishii S., Clark A. J., Sullivan M., Wilson R. K., Ma D. P., Roe B. A., Merlino G. T., Pastan I. Human epidermal growth factor receptor cDNA is homologous to a variety of RNAs overproduced in A431 carcinoma cells. 1984 Jun 28-Jul 4Nature. 309(5971):806–810. doi: 10.1038/309806a0. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. 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]
  41. 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 British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES