Abstract
We have investigated the possibility that structural alterations of the 'nuclear' oncogene family (c-myc, N-myc, L-myc, fos, myb and p53) leading to aberrant expression might, as in several other tumour types, play a role in the multi-stage development of tumorigenesis in the human thyroid follicular cell. Direct analysis of expression by slot and Northern blot RNA hybridisation showed that normal thyroid expresses surprisingly high levels of fos, and to a lesser extent c-myc, c-myc expression was markedly increased in all tumours, both benign and malignant, but no increase was seen in any other nuclear oncogene. fos expression was reduced specifically in one type of malignant tumour-follicular carcinoma-in inverse correlation with differentiation. Southern blot analysis showed no evidence of rearrangement or amplification of c-myc, or of any other 'nuclear' oncogene in any thyroid tumour. We conclude that there is no evidence that a primary abnormality of these genes plays a role in thyroid follicular cell tumorigenesis and suggest that the observed changes in expression can be adequately explained as secondary consequences of the tumour phenotype.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aasland R., Lillehaug J. R., Male R., Jøsendal O., Varhaug J. E., Kleppe K. Expression of oncogenes in thyroid tumours: coexpression of c-erbB2/neu and c-erbB. Br J Cancer. 1988 Apr;57(4):358–363. doi: 10.1038/bjc.1988.82. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boultwood J., Wyllie F. S., Williams E. D., Wynford-Thomas D. N-myc expression in neoplasia of human thyroid C-cells. Cancer Res. 1988 Jul 15;48(14):4073–4077. [PubMed] [Google Scholar]
- Brennand J., Konecki D. S., Caskey C. T. Expression of human and Chinese hamster hypoxanthine-guanine phosphoribosyltransferase cDNA recombinants in cultured Lesch-Nyhan and Chinese hamster fibroblasts. J Biol Chem. 1983 Aug 25;258(16):9593–9596. [PubMed] [Google Scholar]
- Calabretta B., Kaczmarek L., Ming P. M., Au F., Ming S. C. Expression of c-myc and other cell cycle-dependent genes in human colon neoplasia. Cancer Res. 1985 Dec;45(12 Pt 1):6000–6004. [PubMed] [Google Scholar]
- Campisi J., Gray H. E., Pardee A. B., Dean M., Sonenshein G. E. Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation. Cell. 1984 Feb;36(2):241–247. doi: 10.1016/0092-8674(84)90217-4. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Erisman M. D., Rothberg P. G., Diehl R. E., Morse C. C., Spandorfer J. M., Astrin S. M. Deregulation of c-myc gene expression in human colon carcinoma is not accompanied by amplification or rearrangement of the gene. Mol Cell Biol. 1985 Aug;5(8):1969–1976. doi: 10.1128/mcb.5.8.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Franchini G., Wong-Staal F., Baluda M. A., Lengel C., Tronick S. R. Structural organization and expression of human DNA sequences related to the transforming gene of avian myeloblastosis virus. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7385–7389. doi: 10.1073/pnas.80.24.7385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fusco A., Berlingieri M. T., Di Fiore P. P., Portella G., Grieco M., Vecchio G. One- and two-step transformations of rat thyroid epithelial cells by retroviral oncogenes. Mol Cell Biol. 1987 Sep;7(9):3365–3370. doi: 10.1128/mcb.7.9.3365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelly K., Cochran B. H., Stiles C. D., Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. doi: 10.1016/0092-8674(83)90092-2. [DOI] [PubMed] [Google Scholar]
- Kruijer W., Cooper J. A., Hunter T., Verma I. M. Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature. 1984 Dec 20;312(5996):711–716. doi: 10.1038/312711a0. [DOI] [PubMed] [Google Scholar]
- Kunkel L. M., Smith K. D., Boyer S. H., Borgaonkar D. S., Wachtel S. S., Miller O. J., Breg W. R., Jones H. W., Jr, Rary J. M. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1245–1249. doi: 10.1073/pnas.74.3.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Land H., Parada L. F., Weinberg R. A. Cellular oncogenes and multistep carcinogenesis. Science. 1983 Nov 18;222(4625):771–778. doi: 10.1126/science.6356358. [DOI] [PubMed] [Google Scholar]
- Lemoine N. R., Mayall E. S., Wyllie F. S., Farr C. J., Hughes D., Padua R. A., Thurston V., Williams E. D., Wynford-Thomas D. Activated ras oncogenes in human thyroid cancers. Cancer Res. 1988 Aug 15;48(16):4459–4463. [PubMed] [Google Scholar]
- Matlashewski G., Lamb P., Pim D., Peacock J., Crawford L., Benchimol S. Isolation and characterization of a human p53 cDNA clone: expression of the human p53 gene. EMBO J. 1984 Dec 20;3(13):3257–3262. doi: 10.1002/j.1460-2075.1984.tb02287.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mitchell R. L., Zokas L., Schreiber R. D., Verma I. M. Rapid induction of the expression of proto-oncogene fos during human monocytic differentiation. Cell. 1985 Jan;40(1):209–217. doi: 10.1016/0092-8674(85)90324-1. [DOI] [PubMed] [Google Scholar]
- Morgan J. I., Curran T. Role of ion flux in the control of c-fos expression. Nature. 1986 Aug 7;322(6079):552–555. doi: 10.1038/322552a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Rabbitts T. H., Hamlyn P. H., Baer R. Altered nucleotide sequences of a translocated c-myc gene in Burkitt lymphoma. Nature. 1983 Dec 22;306(5945):760–765. doi: 10.1038/306760a0. [DOI] [PubMed] [Google Scholar]
- Rauscher F. J., 3rd, Cohen D. R., Curran T., Bos T. J., Vogt P. K., Bohmann D., Tjian R., Franza B. R., Jr Fos-associated protein p39 is the product of the jun proto-oncogene. Science. 1988 May 20;240(4855):1010–1016. doi: 10.1126/science.3130660. [DOI] [PubMed] [Google Scholar]
- Reuse S., Roger P. P., Vassart G., Dumont J. E. Enhancement of cmyc mRNA concentration in dog thyrocytes initiating DNA synthesis in response to thyrotropin, forskolin, epidermal growth factor and phorbol myristate ester. Biochem Biophys Res Commun. 1986 Dec 30;141(3):1066–1076. doi: 10.1016/s0006-291x(86)80152-8. [DOI] [PubMed] [Google Scholar]
- Ridley A. J., Paterson H. F., Noble M., Land H. Ras-mediated cell cycle arrest is altered by nuclear oncogenes to induce Schwann cell transformation. EMBO J. 1988 Jun;7(6):1635–1645. doi: 10.1002/j.1460-2075.1988.tb02990.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ryseck R. P., Hirai S. I., Yaniv M., Bravo R. Transcriptional activation of c-jun during the G0/G1 transition in mouse fibroblasts. Nature. 1988 Aug 11;334(6182):535–537. doi: 10.1038/334535a0. [DOI] [PubMed] [Google Scholar]
- Sawey M. J., Hood A. T., Burns F. J., Garte S. J. Activation of c-myc and c-K-ras oncogenes in primary rat tumors induced by ionizing radiation. Mol Cell Biol. 1987 Feb;7(2):932–935. doi: 10.1128/mcb.7.2.932. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwab M., Alitalo K., Klempnauer K. H., Varmus H. E., Bishop J. M., Gilbert F., Brodeur G., Goldstein M., Trent J. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature. 1983 Sep 15;305(5931):245–248. doi: 10.1038/305245a0. [DOI] [PubMed] [Google Scholar]
- Schwab M., Ellison J., Busch M., Rosenau W., Varmus H. E., Bishop J. M. Enhanced expression of the human gene N-myc consequent to amplification of DNA may contribute to malignant progression of neuroblastoma. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4940–4944. doi: 10.1073/pnas.81.15.4940. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sikora K., Chan S., Evan G., Gabra H., Markham N., Stewart J., Watson J. c-myc oncogene expression in colorectal cancer. Cancer. 1987 Apr 1;59(7):1289–1295. doi: 10.1002/1097-0142(19870401)59:7<1289::aid-cncr2820590710>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
- Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weinberg R. A. The action of oncogenes in the cytoplasm and nucleus. Science. 1985 Nov 15;230(4727):770–776. doi: 10.1126/science.2997917. [DOI] [PubMed] [Google Scholar]