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Gene Review

EGF  -  epidermal growth factor

Gallus gallus

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Disease relevance of EGF

  • Chicken heart mesenchymal cells do not proliferate in culture medium containing heat-defibrinogenated plasma but proliferate briskly when incubated with epidermal growth factor (EGF) or brain fibroblast growth factor (bFGF) plus insulin-like growth factors (IGFs) or when infected with sarcoma or erythroblastosis viruses [1].
  • In epidermis which was induced to differentiation toward keratinization by hydrocortisone or mucous metaplasia by retinol, EGF inhibited DNA synthesis [2].
  • All hatched chicks were found to express vector-encoded EGFP gene, which was under the control of the Rous sarcoma virus promoter and boosted post-transcriptionally by woodchuck hepatitis virus post-transcriptional regulatory element sequence [3].
  • Here, we successfully demonstrate expression of the EGFP (enhanced green fluorescence protein) gene in chickens using replication-defective MLV (murine leukemia virus)-based retrovirus vectors encapsidated with VSV-G (vesicular stomatitis virus G glycoprotein) [4].
  • Distribution studies were done using plasmids encoding enhanced green fluorescent protein (EGFP) reporter gene and a bivalent DNA vaccine coding for infectious bursal disease virus (IBDV) and Newcastle disease virus (NDV) immunogenic protein genes [5].

High impact information on EGF

  • Heparin-treated MC29-infected cells are, however, 100 times more sensitive to EGF than are their normal, uninfected counterparts [1].
  • Both the 80-kilodalton (kDa) (A) and the 105-kDa (B) progesterone receptor subunits were phosphorylated in a reaction that required EGF and EGF receptor [6].
  • The increase in tyrosine phosphorylation after serum or EGF stimulation was transient, reaching a maximum at about 5 min and then declining [7].
  • By fine-resolution analysis of proteins separated on sodium dodecyl sulfate-polyacrylamide gels, we found that after EGF stimulation, the major increase in phosphotyrosine content was in a 42K Mr protein, with a smaller increase in a 40K Mr protein [7].
  • Both the insulin and EGF receptors phosphorylated progesterone receptor at high affinity, exclusively at tyrosine residues and with maximal stoichiometries that were near unity [8].

Biological context of EGF


Anatomical context of EGF

  • Increased tyrosine phosphorylation of proteins of similar Mr was found in 3T3 cells treated with EGF, but not in NR-6 cells, which lack detectable EGF receptors [7].
  • We found that exogenous TGF-alpha and EGF can promote the outgrowth of limb mesoderm in the absence of the AER in vitro and can also promote the outgrowth of limbless and wingless wing bud explants [9].
  • EGF is present in ventral but not dorsal limb ectoderm, suggesting a role for EGF in specification of ventral ectoderm [9].
  • These studies suggest for the first time that intracellular alkalinization resulting from activation of the Na+/H+ antiporter may be a part of the transmembrane signaling pathway in the action of EGF on chicken granulosa cells [11].
  • This work indicates that the related tyrosyl kinase receptors of insulin and EGF may provoke identical responses within hepatocytes, but through the utilization of different transduction systems which merge to common control points [12].

Associations of EGF with chemical compounds

  • Purified preparations of insulin, epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) receptors were compared for their abilities to phosphorylate purified hen oviduct progesterone receptors [8].
  • For comparison with the growth-promotive effect of the posterior fragment, fibroblast growth factor (FGF), epidermal growth factor (EGF), insulin, and retinoic acid were tested in cell culture [13].
  • Estradiol or epidermal growth factor (EGF) induce a 40% increase in cells in 4 days when cultures are grown in serum levels that do not support growth [14].
  • When a 13-day-old chick embryonic tarsometatarsal skin was cultured for 4 days in medium containing hydrocortisone (20 nM) and 5% delipidized fetal calf serum (FCS), epidermal growth factor (EGF, 100 ng/ml) decreased epidermal DNA content 42% and inhibited epidermal DNA synthesis 87% [15].
  • In the absence of FCS, however, EGF did not inhibit steroid-induced alpha-type keratinization and did not affect either steroid-induced epidermal transglutaminase activity or amount of epidermal glucocorticoid receptor [15].

Regulatory relationships of EGF

  • Furthermore, EGF caused a twofold increase in glucocorticoid-induced epidermal transglutaminase activity and in the amount of epidermal glucocorticoid receptor [15].
  • Transforming growth factor-alpha (TGF-alpha) is a 50 amino acid polypeptide which has been shown to stimulate proliferation in both neoplastic and normal cell types acting through the epidermal growth factor (EGF) receptor [16].

Other interactions of EGF

  • By contrast, theca cell PA activity was not significantly altered by EGF (16.4 nM), IGF-I (131 nM), FGF (7.5 nM), or PDGF (1 nM) [17].
  • Of the other factors known to be present in bone, platelet-derived growth factor (PDGFA/B) and epidermal growth factor (EGF) had a small effect on calcium mobilization but had no effect on ALP activity. bFGF reduced ALP activity slightly without an effect on calcium metabolism [18].
  • Fibronectin secreted into the medium by unstimulated cells also increased with the stage of follicular maturation and was enhanced by EGF and TGF-alpha [19].
  • The present studies were conducted to establish interactions between transforming growth factor (TGF)-beta and the epidermal growth factor (EGF) family members, TGFalpha and betacellulin (BTC), relative to proliferation and differentiation of granulosa cells in hen ovarian follicles [20].

Analytical, diagnostic and therapeutic context of EGF


  1. Heparin-treated, v-myc-transformed chicken heart mesenchymal cells assume a normal morphology but are hypersensitive to epidermal growth factor (EGF) and brain fibroblast growth factor (bFGF); cells transformed by the v-Ha-ras oncogene are refractory to EGF and bFGF but are hypersensitive to insulin-like growth factors. Balk, S.D., Riley, T.M., Gunther, H.S., Morisi, A. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  2. Inhibition by epidermal growth factor (EGF) of epidermal DNA synthesis in cultured chick embryonic skin pretreated with retinol and/or hydrocortisone: specific increment in EGF binding activity in both retinol- and hydrocortisone-pretreated epidermis without correlation to EGF-mediated inhibition of cell growth. Obinata, A., Endo, H. Endocrinol. Jpn. (1992) [Pubmed]
  3. Development of transgenic chickens expressing enhanced green fluorescent protein. Kwon, M.S., Koo, B.C., Choi, B.R., Lee, H.T., Kim, Y.H., Ryu, W.S., Shim, H., Kim, J.H., Kim, N.H., Kim, T. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  4. Retrovirus-mediated gene transfer and expression of EGFP in chicken. Koo, B.C., Kwon, M.S., Choi, B.R., Lee, H.T., Choi, H.J., Kim, J.H., Kim, N.H., Jeon, I., Chang, W., Kim, T. Mol. Reprod. Dev. (2004) [Pubmed]
  5. A novel transcutaneous plasmid-dimethylsulfoxide delivery technique for avian nucleic acid immunization. Heckert, R.A., Elankumaran, S., Oshop, G.L., Vakharia, V.N. Vet. Immunol. Immunopathol. (2002) [Pubmed]
  6. Progesterone receptor subunits are high-affinity substrates for phosphorylation by epidermal growth factor receptor. Ghosh-Dastidar, P., Coty, W.A., Griest, R.E., Woo, D.D., Fox, C.F. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  7. Tyrosine phosphorylation of specific proteins after mitogen stimulation of chicken embryo fibroblasts. Nakamura, K.D., Martinez, R., Weber, M.J. Mol. Cell. Biol. (1983) [Pubmed]
  8. Differential phosphorylation of the progesterone receptor by insulin, epidermal growth factor, and platelet-derived growth factor receptor tyrosine protein kinases. Woo, D.D., Fay, S.P., Griest, R., Coty, W., Goldfine, I., Fox, C.F. J. Biol. Chem. (1986) [Pubmed]
  9. Roles of transforming growth factor-alpha and epidermal growth factor in chick limb development. Dealy, C.N., Scranton, V., Cheng, H.C. Dev. Biol. (1998) [Pubmed]
  10. Analysis of a tyrosine-specific protein kinase activity associated with the retroviral erbB oncogene product. Heimann, B., Beimling, P., Pfaff, E., Schaller, H., Moelling, K. Exp. Cell Res. (1985) [Pubmed]
  11. Epidermal growth factor elevates intracellular pH in chicken granulosa cells. Li, M., Morley, P., Asem, E.K., Tsang, B.K. Endocrinology (1991) [Pubmed]
  12. Control of glycolysis in cultured chick embryo hepatocytes. Fructose 2,6-bisphosphate content and phosphofructokinase-1 activity are stimulated by insulin and epidermal growth factor. Hamer, M.J., Dickson, A.J. Biochem. J. (1990) [Pubmed]
  13. A gradient of responsiveness to the growth-promoting activity of ZPA (zone of polarizing activity) in the chick limb bud. Aono, H., Ide, H. Dev. Biol. (1988) [Pubmed]
  14. The chick oviduct in tissue culture. I. Initial characterization of growing primary oviduct tissue cultures. Seaver, S.S., van der Bosch, J., Sato, G. Exp. Cell Res. (1984) [Pubmed]
  15. Inhibition by epidermal growth factor of glucocorticoid-induced epidermal alpha-type keratinization of chick embryonic skin cultured in the presence of delipidized fetal calf serum. Obinata, A., Akimoto, Y., Hoshino, A., Hirano, H., Endo, H. Dev. Biol. (1987) [Pubmed]
  16. Effects of transforming growth factor-alpha on chicken adipocyte precursor cells in vitro. Butterwith, S.C., Peddie, C.D., Goddard, C. J. Endocrinol. (1992) [Pubmed]
  17. Effect of several growth factors on plasminogen activator activity in granulosa and theca cells of the domestic hen. Tilly, J.L., Johnson, A.L. Poult. Sci. (1990) [Pubmed]
  18. Individual and combined effects of calciotropic hormones and growth factors on mineral metabolism in embryonic chick tibiae. Duvos, C., Scutt, A., Mayer, H. In Vitro Cell. Dev. Biol. Anim. (1997) [Pubmed]
  19. Stimulation of fibronectin production and deposition by chicken granulosa cells in vitro by epidermal growth factor and transforming growth factor alpha. Asem, E.K., Novero, R.P. J. Reprod. Fertil. (1994) [Pubmed]
  20. Opposing actions of TGFbeta and MAP kinase signaling in undifferentiated hen granulosa cells. Woods, D.C., Haugen, M.J., Johnson, A.L. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  21. Germinal disc-derived epidermal growth factor: a paracrine factor to stimulate proliferation of granulosa cells. Yao, H.H., Bahr, J.M. Biol. Reprod. (2001) [Pubmed]
  22. Epidermal growth factor in the germinal disc and its potential role in follicular development in the chicken. Volentine, K.K., Yao, H.H., Bahr, J.M. Biol. Reprod. (1998) [Pubmed]
  23. Epidermal growth factor (EGF)-induced morphological changes in the basement membrane of chick embryonic skin. An electron-microscopic study. Akimoto, Y., Obinata, A., Endo, H., Hirano, H. Cell Tissue Res. (1988) [Pubmed]
  24. Induction of supernumerary tracheal buds and the stimulation of DNA synthesis in the embryonic chick lung and trachea by epidermal growth factor. Goldin, G.V., Opperman, L.A. Journal of embryology and experimental morphology. (1980) [Pubmed]
  25. Behavior of embryonic chick heart cells in culture. 2. Cellular responses to epidermal growth factor and other growth signals. Lau, C.L. Tissue & cell. (1993) [Pubmed]
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