Comparison of epidermal growth factor binding and receptor distribution in normal human epidermis and epidermal appendages.

To localize epidermal growth factor (EGF) receptors in normal human epidermis and other skin structures, two different light microscopic methods were used. EGF binding [( 125I]EGF/R) to the extracellular portion of the EGF receptor was studied by incubating intact skin samples with [125I]EGF, sectioning the tissues, and performing autoradiography. Immunoreactive EGF receptor molecules (IR-EGF/R) were localized with a mono-specific anti-EGF receptor antibody using a 2-step indirect immunocytochemical method (horseradish peroxidase) and detergent permeabilized tissues. This latter method measured the total pool of EGF receptors: occupied and/or internalized forms, precursor forms, and partially degraded forms of the EGF receptor that retain immunoreactivity. Both the [125I]EGF/R and IR-EGF/R localization studies indicated that EGF receptors were present in basal epidermal keratinocytes, sebocytes, outer root sheath cells in hair follicles, smooth muscle cells of arrector pili muscles, and dermal arteries. The highest levels of [125I]EGF/R and IR-EGF/R were found in the dermal ducts of eccrine sweat glands. The distribution of both [125I]EGF/R and IR-EGF/R was not consistent with the concept that EGF exclusively is involved in cellular division and proliferation in normal human epidermis and its appendages, i.e., EGF receptors were also found in tissues that do not undergo rapid proliferation. The present study indicates that EGF may have a more complex regulatory role in the skin than was previously thought.

[1]  L. King,et al.  Surface iodination of epidermal growth factor receptors in intact cells. , 1984, The Journal of investigative dermatology.

[2]  G. Chader,et al.  Protein tyrosine kinase and protein phosphotyrosine phosphatase in normal and psoriatic skin. , 1984, Biochimica et biophysica acta.

[3]  R. Lim,et al.  A rapid decrease in epidermal growth factor-binding capacity accompanies the terminal differentiation of mouse myoblasts in vitro , 1984, The Journal of cell biology.

[4]  G. Carpenter,et al.  Visualization of epidermal growth factor receptors in human epidermis. , 1984, The Journal of investigative dermatology.

[5]  D. Basketter,et al.  Distribution and number of epidermal growth factor receptors in skin is related to epithelial cell growth. , 1983, Developmental biology.

[6]  G. Carpenter,et al.  Characteristics of antibodies to the epidermal growth factor receptor-kinase. , 1983, Archives of biochemistry and biophysics.

[7]  E. O'Keefe,et al.  Modulation of the epidermal growth factor receptor of human keratinocytes by calcium ion. , 1983, The Journal of investigative dermatology.

[8]  G. Carpenter,et al.  Characteristics and uses of antibodies to the EGF-receptor kinase , 1983 .

[9]  N. Orentreich,et al.  Stimulation of hamster sebaceous glands by epidermal growth factor. , 1983, The Journal of investigative dermatology.

[10]  J. Hanker,et al.  Neutrophil pseudoplatelets: their discrimination by myeloperoxidase demonstration. , 1983, Science.

[11]  R. Ross,et al.  Interactions between the receptors for platelet-derived growth factor and epidermal growth factor , 1983, The Journal of cell biology.

[12]  D. Robertson,et al.  Epidermal growth factor delays the development of the epidermis and hair follicles of mice during growth of the first coat , 1983, The Anatomical record.

[13]  C. Ho,et al.  Preparation and proton nuclear magnetic resonance investigation of cross-linked mixed valency hybrid hemoglobins: models for partially oxygenated species. , 1982, Biochemistry.

[14]  E. O'Keefe,et al.  Epidermal growth factor receptor in human epidermal cells: direct demonstration in cultured cells. , 1982, The Journal of investigative dermatology.

[15]  L. Dubertret,et al.  Diaminobenzidine cytochemistry in unfixed human epidermis: a marker for epidermal differentiation and for mitochondria. , 1982, The Journal of investigative dermatology.

[16]  M. Collins,et al.  Inhibition of epidermal growth factor binding to mouse cultured cells by fibroblast-derived growth factor. Evidence for an indirect mechanism. , 1982, The Journal of biological chemistry.

[17]  Michael Chinkers,et al.  A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles. , 1982, The Journal of biological chemistry.

[18]  S. Cohen,et al.  Enhancement of calcium uptake and phosphatidylinositol turnover by epidermal growth factor in A-431 cells. , 1981, Biochemistry.

[19]  L. Orci,et al.  The fate of [125I]iodoepidermal growth factor in isolated hepatocytes: a quantitative electron microscopic autoradiographic study. , 1981, Endocrinology.

[20]  J. Grinsted,et al.  Feminizing effect of mesonephros on cultured differentiating mouse gonads and ducts. , 1981, Science.

[21]  T. Maciag,et al.  Hormonal requirements for growth of arterial smooth muscle cells in vitro: and endocrine approach to atherosclerosis. , 1981, Science.

[22]  M. Sofroniew,et al.  Golgi-like immunoperoxidase staining of hypothalamic magnocellular neurons that contain vasopressin, oxytocin or neurophysin in the rat , 1981, Neuroscience.

[23]  D. Robertson,et al.  Effects of epidermal growth factor on hair growth in the mouse. , 1981, The Journal of endocrinology.

[24]  E. Rozengurt,et al.  Vasopressin inhibition of epidermal growth factor binding to cultured mouse cells. , 1981, The Journal of biological chemistry.

[25]  S. Cohen,et al.  Hormone receptor topology and dynamics: morphological analysis using ferritin-labeled epidermal growth factor. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[26]  I. Weinstein,et al.  Mechanism of tumor promoter inhibition of cellular binding of epidermal growth factor. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[27]  S. Cohen,et al.  Direct visualization of the binding and internalization of a ferritin conjugate of epidermal growth factor in human carcinoma cells A-431 , 1979, The Journal of cell biology.

[28]  L. Orci,et al.  Epidermal growth factor: morphological demonstration of binding, internalization, and lysosomal association in human fibroblasts. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[29]  S. Singer,et al.  Visualization by fluorescence of the binding and internalization of epidermal growth factor in human carcinoma cells A-431. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[30]  I. Pastan,et al.  Direct visualization of binding, aggregation, and internalization of insulin and epidermal growth factor on living fibroblastic cells. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[31]  D. Orth,et al.  Radioimmunoassay of human epidermal growth factor (urogastrone). , 1977, The Journal of clinical endocrinology and metabolism.

[32]  G. Todaro,et al.  Nerve growth factor receptors on human melanoma cells in culture. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[33]  G. Carpenter,et al.  125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts , 1976, The Journal of cell biology.

[34]  S. Cohen,et al.  Epidermal growth factor: identification of a new hormone in human urine. , 1975, Science.

[35]  H. Gregory Isolation and structure of urogastrone and its relationship to epidermal growth factor , 1975, Nature.

[36]  G. Carpenter,et al.  Characterization of the binding of 125-I-labeled epidermal growth factor to human fibroblasts. , 1975, The Journal of biological chemistry.

[37]  P. Cuatrecasas,et al.  Insulin and epidermal growth factor. Human fibroblast receptors related to deoxyribonucleic acid synthesis and amino acid uptake. , 1975, The Journal of biological chemistry.

[38]  P. Cuatrecasas,et al.  Epidermal growth factor. Characteristics of specific binding in membranes from liver, placenta, and other target tissues. , 1974, Archives of biochemistry and biophysics.

[39]  S. Cohen,et al.  Epidermal growth factor: effects of androgens and adrenergic agents. , 1974, Endocrinology.

[40]  L. Frati,et al.  Synthesis of bioactive 131 I-labeled epidermal growth factor and its distribution in rat tissues. , 1972, European journal of biochemistry.

[41]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[42]  S. Cohen,et al.  The stimulation of epidermal proliferation by a specific protein (EGF). , 1965, Developmental biology.

[43]  D. Robertson,et al.  Inhibition of wool growth in merino sheep following administration of mouse epidermal growth factor and a derivative. , 1982, Australian journal of biological sciences.

[44]  J. Baker,et al.  Glucocorticoid-mediated alteration in growth factor binding and action: analysis of the binding change. , 1978, Journal of supramolecular structure.

[45]  J. Garvey Methods in immunology , 1977 .

[46]  S. Cohen,et al.  Recent studies on the chemistry and biology of epidermal growth factor. , 1974, Recent progress in hormone research.

[47]  S. Cohen,et al.  The stimulation of epidermal keratinization by a protein isolated from the submaxillary gland of the mouse. , 1963, The Journal of investigative dermatology.