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Gene Review

Egfr  -  epidermal growth factor receptor

Mus musculus

Synonyms: 9030024J15Rik, AI552599, Epidermal growth factor receptor, Erbb, Errb1, ...
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Disease relevance of Egfr

  • Newborn Egfr-/- mice have facial mediolateral defects including narrow, elongated snouts, underdeveloped lower jaw and a high incidence of cleft palate [1].
  • Treatment with EKI-785 produced a dose-dependent reduction in tumor growth, suggesting that Egfr inhibitors may be useful for advanced colorectal cancer treatment [2].
  • Surprisingly, the size, expansion, and pathological progression of the polyps appear Egfr-independent [2].
  • Transfer of the Apc(Min) allele onto a homozygous Egfr(wa2) background results in a 90% reduction in intestinal polyp number relative to Apc(Min) mice carrying a wild-type Egfr allele [2].
  • Genetic ablation of Egfr similarly delayed epidermal hyperplasia in response to UV exposure [3].

Psychiatry related information on Egfr

  • To study the role of EGF, TGF-alpha and EGFR in early human development, two methods applicable for analysis of expression at the single embryo level have been employed [4].
  • Although the female transgenic mice possessing mutant EGFR developed mammary tumors, the tumors occurred only after a delayed latency period, and were fewer in number [5].
  • Our results also suggest that other uncontrolled genetic or environmental parameters confounded previous experiments linking EGFR activity to daily locomotor activity and provide a cautionary tale for genetically uncontrolled studies [6].

High impact information on Egfr


Chemical compound and disease context of Egfr


Biological context of Egfr

  • In addition, morphogenesis of Meckel's cartilage was deficient in cultured mandibular processes from Egfr-/- embryos [1].
  • The severity of the phenotypes correlates with the expression levels of the hEGFRKI allele, which is not efficiently expressed in epithelial and bone cells, but is expressed at similar and even higher levels as the endogenous Egfr in brain and heart [16].
  • Ductal growth and development was normal in transplants of mammary epithelium from Egfr-/- mice into wild-type (WT) gland-free fat pads and in tissue recombinants prepared with WT stroma, irrespective of the source of epithelium (StromaWT/Epi-/-, StromaWT/EpiWT) [17].
  • The Ikaros gene maps at a syntenic locus located on the short arm of human chromosome 7 and on mouse chromosome 11 next to the epidermal growth factor receptor (Egfr) [18].
  • Egfr, localized on proximal chromosome 11, is amplified two to three times and leads to an easily identifiable, stable marker chromosome with a large amplification unit, which is present in each metaphase [19].

Anatomical context of Egfr


Associations of Egfr with chemical compounds

  • Inhibition of endogenous Egfr signaling with the Egfr inhibitor gefitinib (Iressa) or replacement of wild-type Egfr with the kinase-deficient protein encoded by the hypomorphic Egfr(wa2) allele completely rescued skin defects in Erffi1(-/-) mice [22].
  • Pharmacological inhibition with EKI-785, an Egfr tyrosine kinase inhibitor, produced similar results in the Apc(Min) model [2].
  • Evidence is provided that phosphorylation and activation of p70(S6K)/p90(RSK) induced by UVA were prevented in Egfr(-/-) cells and were also markedly inhibited by the EGFR-specific tyrosine kinase inhibitors AG1478 and PD153035 [23].
  • PURPOSE: Therefore, we have studied the role of EGF-R expression on cisplatin-mediated cytotoxicity [24].
  • Additionally, EGFR protein expression was down-regulated in response to estrogen and up-regulated in response to fulvestrant in vitro, suggesting that the EGFR pathway is activated when estrogen is depleted in NSCLC cells [25].

Physical interactions of Egfr


Enzymatic interactions of Egfr


Regulatory relationships of Egfr

  • Moreover, we observe a concordant loss of Pten and EGFR overexpression in nearly all high-grade gliomas induced by either EGFRvIII introduction or Pten inactivation [36].
  • Several EGFR agonists also stimulated Adam17(-/-) mammary organoid growth in culture, but only AREG was expressed abundantly in the developing ductal system in vivo [37].
  • We found that EGF continues to stimulate maximal tyrosine phosphorylation of EGFR following internalization, while, as expected, TGFalpha stimulates markedly less [38].
  • Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth factor receptor ligand availability [39].
  • With differential ligand-induced internalization and trafficking-restricted receptor variants, we find that calpain activity is triggered only by plasma membrane-restricted activated EGFR, not by internalized (although still active) EGFR [40].

Other interactions of Egfr


Analytical, diagnostic and therapeutic context of Egfr

  • Because Egfr-/- mice die perinatally, transplantation methods were used to study these processes [17].
  • However, UV exposure increased cell proliferation, as measured by Ki67 immunohistochemistry and proliferating cell nuclear antigen immunoblotting, maximally at 48 h to a level more than three times higher in wild-type compared with Egfr-null skin [45].
  • Apoptotic cell death, as measured by terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) analysis, was also increased in UV-exposed Egfr-null skin when compared with wild-type 1-2 days post-UV [45].
  • Expression profiling using microarrays, which was selectively validated and extended by immunophenotyping of Neu*-induced PIN and CAP, led to the identification of some novel biomarkers and also revealed increased expression of Egfr, Erbb3 and phosphorylated androgen receptor [46].
  • RESULTS: Selected clones (MDA-468/AS-EGFR) exhibited more than 90% loss of both 125I-EGF binding and receptor content determined by western blot analysis, whereas clones transfected with the vector alone (MDA-468/p-CAT) had EGF-R levels similar to those of the parent cells [24].


  1. Epidermal growth factor receptor function is necessary for normal craniofacial development and palate closure. Miettinen, P.J., Chin, J.R., Shum, L., Slavkin, H.C., Shuler, C.F., Derynck, R., Werb, Z. Nat. Genet. (1999) [Pubmed]
  2. Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis. Roberts, R.B., Min, L., Washington, M.K., Olsen, S.J., Settle, S.H., Coffey, R.J., Threadgill, D.W. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  3. Chemoprevention of UV light-induced skin tumorigenesis by inhibition of the epidermal growth factor receptor. El-Abaseri, T.B., Fuhrman, J., Trempus, C., Shendrik, I., Tennant, R.W., Hansen, L.A. Cancer Res. (2005) [Pubmed]
  4. EGF, TGF-alpha and EGFR expression in human preimplantation embryos. Chia, C.M., Winston, R.M., Handyside, A.H. Development (1995) [Pubmed]
  5. Epidermal growth factor receptor-dependent activation of Gab1 is involved in ErbB-2-mediated mammary tumor progression. Gillgrass, A., Cardiff, R.D., Sharan, N., Kannan, S., Muller, W.J. Oncogene (2003) [Pubmed]
  6. Wildtype epidermal growth factor receptor (Egfr) is not required for daily locomotor or masking behavior in mice. Roberts, R.B., Thompson, C.L., Lee, D., Mankinen, R.W., Sancar, A., Threadgill, D.W. Journal of circadian rhythms (2006) [Pubmed]
  7. An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Zhang, X., Gureasko, J., Shen, K., Cole, P.A., Kuriyan, J. Cell (2006) [Pubmed]
  8. EGF receptor activation: push comes to shove. Hubbard, S.R. Cell (2006) [Pubmed]
  9. Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha. Garrett, T.P., McKern, N.M., Lou, M., Elleman, T.C., Adams, T.E., Lovrecz, G.O., Zhu, H.J., Walker, F., Frenkel, M.J., Hoyne, P.A., Jorissen, R.N., Nice, E.C., Burgess, A.W., Ward, C.W. Cell (2002) [Pubmed]
  10. Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis. Chen, B., Bronson, R.T., Klaman, L.D., Hampton, T.G., Wang, J.F., Green, P.J., Magnuson, T., Douglas, P.S., Morgan, J.P., Neel, B.G. Nat. Genet. (2000) [Pubmed]
  11. Targeted disruption of the epidermal growth factor receptor impairs growth of squamous papillomas expressing the v-ras(Ha) oncogene but does not block in vitro keratinocyte responses to oncogenic ras. Dlugosz, A.A., Hansen, L., Cheng, C., Alexander, N., Denning, M.F., Threadgill, D.W., Magnuson, T., Coffey, R.J., Yuspa, S.H. Cancer Res. (1997) [Pubmed]
  12. PTEN/Akt signaling through epidermal growth factor receptor is prerequisite for angiogenesis by hepatocellular carcinoma cells that is susceptible to inhibition by gefitinib. Ueda, S., Basaki, Y., Yoshie, M., Ogawa, K., Sakisaka, S., Kuwano, M., Ono, M. Cancer Res. (2006) [Pubmed]
  13. Abrogation of transforming growth factor-alpha/epidermal growth factor receptor autocrine signaling by an RXR-selective retinoid (LGD1069, Targretin) in head and neck cancer cell lines. Song, J.I., Lango, M.N., Hwang, J.D., Drenning, S.D., Zeng, Q., Lamph, W.W., Grandis, J.R. Cancer Res. (2001) [Pubmed]
  14. Tyrosine kinase activity of the EGF receptor in murine metanephric organ culture. Pugh, J.L., Sweeney, W.E., Avner, E.D. Kidney Int. (1995) [Pubmed]
  15. Mice harboring a defective epidermal growth factor receptor (waved-2) have an increased susceptibility to acute dextran sulfate-induced colitis. Egger, B., Büchler, M.W., Lakshmanan, J., Moore, P., Eysselein, V.E. Scand. J. Gastroenterol. (2000) [Pubmed]
  16. Mice humanised for the EGF receptor display hypomorphic phenotypes in skin, bone and heart. Sibilia, M., Wagner, B., Hoebertz, A., Elliott, C., Marino, S., Jochum, W., Wagner, E.F. Development (2003) [Pubmed]
  17. Signaling through the stromal epidermal growth factor receptor is necessary for mammary ductal development. Wiesen, J.F., Young, P., Werb, Z., Cunha, G.R. Development (1999) [Pubmed]
  18. The Ikaros gene encodes a family of lymphocyte-restricted zinc finger DNA binding proteins, highly conserved in human and mouse. Molnár, A., Wu, P., Largespada, D.A., Vortkamp, A., Scherer, S., Copeland, N.G., Jenkins, N.A., Bruns, G., Georgopoulos, K. J. Immunol. (1996) [Pubmed]
  19. Murine pancreatic tumor cell line TD2 bears the characteristic pattern of genetic changes with two independently amplified gene loci. Schreiner, B., Greten, F.R., Baur, D.M., Fingerle, A.A., Zechner, U., Böhm, C., Schmid, M., Hameister, H., Schmid, R.M. Oncogene (2003) [Pubmed]
  20. Apc deficiency is associated with increased Egfr activity in the intestinal enterocytes and adenomas of C57BL/6J-Min/+ mice. Moran, A.E., Hunt, D.H., Javid, S.H., Redston, M., Carothers, A.M., Bertagnolli, M.M. J. Biol. Chem. (2004) [Pubmed]
  21. Signaling through the EGF receptor controls lung morphogenesis in part by regulating MT1-MMP-mediated activation of gelatinase A/MMP2. Kheradmand, F., Rishi, K., Werb, Z. J. Cell. Sci. (2002) [Pubmed]
  22. Mig6 is a negative regulator of EGF receptor-mediated skin morphogenesis and tumor formation. Ferby, I., Reschke, M., Kudlacek, O., Knyazev, P., Pantè, G., Amann, K., Sommergruber, W., Kraut, N., Ullrich, A., Fässler, R., Klein, R. Nat. Med. (2006) [Pubmed]
  23. Induction of EGFR-dependent and EGFR-independent signaling pathways by ultraviolet A irradiation. Zhang, Y., Dong, Z., Bode, A.M., Ma, W.Y., Chen, N., Dong, Z. DNA Cell Biol. (2001) [Pubmed]
  24. Abrogation of cisplatin-induced programmed cell death in human breast cancer cells by epidermal growth factor antisense RNA. Dixit, M., Yang, J.L., Poirier, M.C., Price, J.O., Andrews, P.A., Arteaga, C.L. J. Natl. Cancer Inst. (1997) [Pubmed]
  25. Combined targeting of the estrogen receptor and the epidermal growth factor receptor in non-small cell lung cancer shows enhanced antiproliferative effects. Stabile, L.P., Lyker, J.S., Gubish, C.T., Zhang, W., Grandis, J.R., Siegfried, J.M. Cancer Res. (2005) [Pubmed]
  26. Neuropeptide-induced transactivation of a neuronal epidermal growth factor receptor is mediated by metalloprotease-dependent formation of heparin-binding epidermal growth factor. Shah, B.H., Farshori, M.P., Catt, K.J. J. Biol. Chem. (2004) [Pubmed]
  27. The Grb2-mSos1 complex binds phosphopeptides with higher affinity than Grb2. Chook, Y.M., Gish, G.D., Kay, C.M., Pai, E.F., Pawson, T. J. Biol. Chem. (1996) [Pubmed]
  28. Phosphorylation of Y845 on the epidermal growth factor receptor mediates binding to the mitochondrial protein cytochrome c oxidase subunit II. Boerner, J.L., Demory, M.L., Silva, C., Parsons, S.J. Mol. Cell. Biol. (2004) [Pubmed]
  29. Contribution of the transforming growth factor alpha B-loop beta-sheet to binding and activation of the epidermal growth factor receptor. Richter, A., Drummond, D.R., MacGarvie, J., Puddicombe, S.M., Chamberlin, S.G., Davies, D.E. J. Biol. Chem. (1995) [Pubmed]
  30. Schwannoma-derived growth factor interacts with the epidermal growth factor receptor. Maher, P.A., Schubert, D. J. Neurochem. (1995) [Pubmed]
  31. A 120 kDa nuclear phospholipase Cgamma1 protein fragment is stimulated in vivo by EGF signal phosphorylating nuclear membrane EGFR. Klein, C., Gensburger, C., Freyermuth, S., Nair, B.C., Labourdette, G., Malviya, A.N. Biochemistry (2004) [Pubmed]
  32. In vitro activation of Stat3 by epidermal growth factor receptor kinase. Park, O.K., Schaefer, T.S., Nathans, D. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  33. A tyrosine-phosphorylated protein of 140 kD is constitutively associated with the phosphotyrosine binding domain of Shc and the SH3 domains of Grb2 in acute myeloid leukemia cells. Jücker, M., Schiffer, C.A., Feldman, R.A. Blood (1997) [Pubmed]
  34. Proteolytic cleavage of phospholipase C-gamma1 during apoptosis in Molt-4 cells. Bae, S.S., Perry, D.K., Oh, Y.S., Choi, J.H., Galadari, S.H., Ghayur, T., Ryu, S.H., Hannun, Y.A., Suh, P.G. FASEB J. (2000) [Pubmed]
  35. Eps15R is a tyrosine kinase substrate with characteristics of a docking protein possibly involved in coated pits-mediated internalization. Coda, L., Salcini, A.E., Confalonieri, S., Pelicci, G., Sorkina, T., Sorkin, A., Pelicci, P.G., Di Fiore, P.P. J. Biol. Chem. (1998) [Pubmed]
  36. High-grade glioma formation results from postnatal pten loss or mutant epidermal growth factor receptor expression in a transgenic mouse glioma model. Wei, Q., Clarke, L., Scheidenhelm, D.K., Qian, B., Tong, A., Sabha, N., Karim, Z., Bock, N.A., Reti, R., Swoboda, R., Purev, E., Lavoie, J.F., Bajenaru, M.L., Shannon, P., Herlyn, D., Kaplan, D., Henkelman, R.M., Gutmann, D.H., Guha, A. Cancer Res. (2006) [Pubmed]
  37. Mammary ductal morphogenesis requires paracrine activation of stromal EGFR via ADAM17-dependent shedding of epithelial amphiregulin. Sternlicht, M.D., Sunnarborg, S.W., Kouros-Mehr, H., Yu, Y., Lee, D.C., Werb, Z. Development (2005) [Pubmed]
  38. Effect of epidermal growth factor receptor internalization on regulation of the phospholipase C-gamma1 signaling pathway. Haugh, J.M., Schooler, K., Wells, A., Wiley, H.S., Lauffenburger, D.A. J. Biol. Chem. (1999) [Pubmed]
  39. Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth factor receptor ligand availability. Sunnarborg, S.W., Hinkle, C.L., Stevenson, M., Russell, W.E., Raska, C.S., Peschon, J.J., Castner, B.J., Gerhart, M.J., Paxton, R.J., Black, R.A., Lee, D.C. J. Biol. Chem. (2002) [Pubmed]
  40. Membrane proximal ERK signaling is required for M-calpain activation downstream of epidermal growth factor receptor signaling. Glading, A., Uberall, F., Keyse, S.M., Lauffenburger, D.A., Wells, A. J. Biol. Chem. (2001) [Pubmed]
  41. Angiotensin II and EGF receptor cross-talk in chronic kidney diseases: a new therapeutic approach. Lautrette, A., Li, S., Alili, R., Sunnarborg, S.W., Burtin, M., Lee, D.C., Friedlander, G., Terzi, F. Nat. Med. (2005) [Pubmed]
  42. Synergistic interaction of the Neu proto-oncogene product and transforming growth factor alpha in the mammary epithelium of transgenic mice. Muller, W.J., Arteaga, C.L., Muthuswamy, S.K., Siegel, P.M., Webster, M.A., Cardiff, R.D., Meise, K.S., Li, F., Halter, S.A., Coffey, R.J. Mol. Cell. Biol. (1996) [Pubmed]
  43. Epidermal growth factor-independent transformation of Ba/F3 cells with cancer-derived epidermal growth factor receptor mutants induces gefitinib-sensitive cell cycle progression. Jiang, J., Greulich, H., Jänne, P.A., Sellers, W.R., Meyerson, M., Griffin, J.D. Cancer Res. (2005) [Pubmed]
  44. Epidermal growth factor receptor-mediated activation of Stat3 during multistage skin carcinogenesis. Chan, K.S., Carbajal, S., Kiguchi, K., Clifford, J., Sano, S., DiGiovanni, J. Cancer Res. (2004) [Pubmed]
  45. Ultraviolet irradiation induces keratinocyte proliferation and epidermal hyperplasia through the activation of the epidermal growth factor receptor. El-Abaseri, T.B., Putta, S., Hansen, L.A. Carcinogenesis (2006) [Pubmed]
  46. Prostatic intraepithelial neoplasia and adenocarcinoma in mice expressing a probasin-Neu oncogenic transgene. Li, Z., Szabolcs, M., Terwilliger, J.D., Efstratiadis, A. Carcinogenesis (2006) [Pubmed]
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