• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of embojLink to Publisher's site
EMBO J. May 1985; 4(5): 1193–1197.
PMCID: PMC554323

Stimulation and inhibition of growth by EGF in different A431 cell clones is accompanied by the rapid induction of c-fos and c-myc proto-oncogenes.


Stimulation of quiescent fibroblasts to growth by polypeptide growth factors is accompanied by the rapid induction of c-fos and c-myc proto-oncogenes. In contrast to fibroblasts, A431 cells respond to epidermal growth factor (EGF) with a decreased growth rate. Here we report that, in spite of its growth inhibitory effect, EGF rapidly induces transient expression of c-fos mRNA, followed by the synthesis of nuclear c-fos protein. In addition, EGF treatment resulted in elevated levels of c-myc expression. Practically identical results were obtained with variant A431 clones that are resistant to the inhibitory effect of EGF on cell proliferation. These observations suggest that in A431 cells c-fos and c-myc induction is a primary consequence of growth factor-receptor interaction. Indeed, efficient induction of both genes was also observed with cyanide bromide-cleaved EGF, which has previously been shown to be non-mitogenic but able to trigger early events induced by EGF. We observed strong induction of c-fos and to a lesser extent of c-myc also by TPA, and by the calcium ionophore A23187, indicating an important role for kinase C in proto-oncogene activation by growth factors.

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 (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Curran T, Peters G, Van Beveren C, Teich NM, Verma IM. FBJ murine osteosarcoma virus: identification and molecular cloning of biologically active proviral DNA. J Virol. 1982 Nov;44(2):674–682. [PMC free article] [PubMed]
  • Curran T, Miller AD, Zokas L, Verma IM. Viral and cellular fos proteins: a comparative analysis. Cell. 1984 Feb;36(2):259–268. [PubMed]
  • Fabricant RN, De Larco JE, Todaro GJ. Nerve growth factor receptors on human melanoma cells in culture. Proc Natl Acad Sci U S A. 1977 Feb;74(2):565–569. [PMC free article] [PubMed]
  • Gill GN, Lazar CS. Increased phosphotyrosine content and inhibition of proliferation in EGF-treated A431 cells. Nature. 1981 Sep 24;293(5830):305–307. [PubMed]
  • Gill GN, Buss JE, Lazar CS, Lifshitz A, Cooper JA. Role of epidermal growth factor-stimulated protein kinase in control of proliferation of A431 cells. J Cell Biochem. 1982;19(3):249–257. [PubMed]
  • Gospodarowicz D, Greenburg G, Bialecki H, Zetter BR. Factors involved in the modulation of cell proliferation in vivo and in vitro: the role of fibroblast and epidermal growth factors in the proliferative response of mammalian cells. In Vitro. 1978 Jan;14(1):85–118. [PubMed]
  • Greenberg ME, Ziff EB. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. [PubMed]
  • Haigler H, Ash JF, Singer SJ, Cohen S. Visualization by fluorescence of the binding and internalization of epidermal growth factor in human carcinoma cells A-431. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3317–3321. [PMC free article] [PubMed]
  • Kelly K, Cochran BH, Stiles CD, 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. [PubMed]
  • Kruijer W, Cooper JA, Hunter T, Verma IM. Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature. 1984 Dec 20;312(5996):711–716. [PubMed]
  • Laskey RA, Mills AD. Quantitative film detection of 3H and 14C in polyacrylamide gels by fluorography. Eur J Biochem. 1975 Aug 15;56(2):335–341. [PubMed]
  • Lin CR, Chen WS, Kruiger W, Stolarsky LS, Weber W, Evans RM, Verma IM, Gill GN, Rosenfeld MG. Expression cloning of human EGF receptor complementary DNA: gene amplification and three related messenger RNA products in A431 cells. Science. 1984 May 25;224(4651):843–848. [PubMed]
  • Lifshitz A, Lazar CS, Buss JE, Gill GN. Analysis of morphology and receptor metabolism in clonal variant A431 cells with differing growth responses to epidermal growth factor. J Cell Physiol. 1983 Jun;115(3):235–242. [PubMed]
  • Merlino GT, Xu YH, Ishii S, Clark AJ, Semba K, Toyoshima K, Yamamoto T, Pastan I. Amplification and enhanced expression of the epidermal growth factor receptor gene in A431 human carcinoma cells. Science. 1984 Apr 27;224(4647):417–419. [PubMed]
  • Müller R, Bravo R, Burckhardt J, Curran T. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature. 1984 Dec 20;312(5996):716–720. [PubMed]
  • Nishizuka Y. Turnover of inositol phospholipids and signal transduction. Science. 1984 Sep 21;225(4668):1365–1370. [PubMed]
  • O'Farrell PH. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed]
  • Schreiber AB, Yarden Y, Schlessinger J. A non-mitogenic analogue of epidermal growth factor enhances the phosphorylation of endogenous membrane proteins. Biochem Biophys Res Commun. 1981 Jul 30;101(2):517–523. [PubMed]
  • Schechter Y, Hernaez L, Schlessinger J, Cuatrecasas P. Local aggregation of hormone-receptor complexes is required for activation by epidermal growth factor. Nature. 1979 Apr 26;278(5707):835–838. [PubMed]
  • Shen-Ong GL, Keath EJ, Piccoli SP, Cole MD. Novel myc oncogene RNA from abortive immunoglobulin-gene recombination in mouse plasmacytomas. Cell. 1982 Dec;31(2 Pt 1):443–452. [PubMed]
  • Smith KB, Losonczy I, Sahai A, Pannerselvam M, Fehnel P, Salomon DS. Effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the growth inhibitory and increased phosphatidylinositol (PI) responses induced by epidermal growth factor (EGF) in A431 cells. J Cell Physiol. 1983 Oct;117(1):91–100. [PubMed]
  • Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW, Lee J, Yarden Y, Libermann TA, Schlessinger J, et al. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature. 309(5967):418–425. [PubMed]
  • Yarden Y, Schreiber AB, Schlessinger J. A nonmitogenic analogue of epidermal growth factor induces early responses mediated by epidermal growth factor. J Cell Biol. 1982 Mar;92(3):687–693. [PMC free article] [PubMed]
  • Armelin HA, Armelin MC, Kelly K, Stewart T, Leder P, Cochran BH, Stiles CD. Functional role for c-myc in mitogenic response to platelet-derived growth factor. Nature. 1984 Aug 23;310(5979):655–660. [PubMed]
  • Bravo R. Epidermal growth factor inhibits the synthesis of the nuclear protein cyclin in A431 human carcinoma cells. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4848–4850. [PMC free article] [PubMed]
  • Bravo R, Small JV, Fey SJ, Larsen PM, Celis JE. Architecture and polypeptide composition of HeLa cytoskeletons. Modification of cytoarchitectural polypeptides during mitosis. J Mol Biol. 1982 Jan 5;154(1):121–143. [PubMed]
  • Buss JE, Kudlow JE, Lazar CS, Gill GN. Altered epidermal growth factor (EGF)-stimulated protein kinase activity in variant A431 cells with altered growth responses to EGF. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2574–2578. [PMC free article] [PubMed]
  • Buss JE, Chouvet C, Gill GN. Comparison of protein phosphorylations in variant A431 cells with different growth responses to epidermal growth factor. J Cell Physiol. 1984 Jun;119(3):296–306. [PubMed]
  • Curran T, Teich NM. Candidate product of the FBJ murine osteosarcoma virus oncogene: characterization of a 55,000-dalton phosphoprotein. J Virol. 1982 Apr;42(1):114–122. [PMC free article] [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • 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...