Summary
The expression of epidermal growth factor (EGF) was examined on various human tissues by radioimmunoassay, immunohistochemistry and Northern blot analysis. Immunoreactive EGF was found in most of the human tissues by radioimmunoassay at various levels. Large quantities of EGF were detected in the kidney and thyroid gland. Immunohistochemically, EGF immunoreactivity was detected mainly in the epithelial cells of the lung, stomach, duodenum, pancreas, kidney, pituitary gland, thyroid gland, mammary gland, ovary, uterus and placenta. Weakly EGF-positive cells were also found in the adrenal gland. The results of EGF-immunostaining were not always consistent with the data from radioimmunoassay. We consider that the amount of EGF measured by radioimmunoassay reflects the density of EGF-positive cells in the tissues and the concentration of EGF in individual EGF-positive cells. Furthermore, EGF mRNA was expressed in the salivary gland, thyroid gland, mammary gland and kidney. It is thus evident that EGF is produced by a variety of human tissues. The kidney expressed exceptionally high levels of EGF mRNA which was about one-tenth of the expression in mouse submandibular gland, suggesting that most of EGF in the urine is produced and secreted by the epithelial cells of renal tubules.
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References
Al-Nafussi AI, Wright NA (1982) The effect of epidermal growth factor (EGF) on cell proliferation of the gastrointestinal mucosa in rodents. Virchows Arch A 40:63–69
Bell GI, Fong NM, Stempien MM, Wormsted MA, Caput DKL, Urdea MS, Rall LB, Sanchez-Pescador R (1986) Human epidermal growth factor precursor: cDNA sequence, expression in vitro and gene organization. Nucleic Acids Res 14:8427–8446
Carpenter G (1981) Epidermal growth factor. Handb Exp Pharmacol 57:90–126
Cohen S (1962) Isolation of a submaxillary gland protein accelerating incisor eruption and eyelid opening in the newborn animal. J Biol Chem 137:1555–1562
Cohen S, Carpenter G (1975) Human epidermal growth factor: isolation and chemical and biological properties. Proc Natl Acad Sci USA 72:1317–1321
Cohen S, Savage CR Jr (1974) Recent studies on the chemistry and biology of epidermal growth factor. Recent Prog Horm Res 30:551–574
Cohen S, Taylar JM (1974) Epidermal growth factor: chemical and biological characterization. Recent Prog Horm Res 30:533–550
Cohen S, Ushiro H, Stocheck C, Chinkers M (1982) A native 170,000 epidermal growth factor receptor-kinase complex from shed membrane vesicles. J Biol Chem 257:1523–1531
Dailey GE, Kraus JW, Orth DN (1978) Homologous radioimmunoassay for human epidermal growth factor (urogastrone). J Clin Endocrinol Metab 46:929–936
Dembinski AB, Johnson LR (1985) Effect of epidermal growth factor on the development of rat gastric mucosa. Endocrinology 116:90–94
Downward J, Yarden Y, Mayes E, Scrace G, Totty N, Stockwell P, Ullrich A, Schlessinger J, Waterfield MD (1984) Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307:521–527
Gregory H (1975) Isolation and structure of urogastrone and its relationship to epidermal growth factor. Nature 257:325–328
Gresik EW, Barka T (1977) Immunocytochemical localization of epidermal growth factor in mouse submandibular gland. J Histochem Cytochem 25:1023–1035
Hirata Y, Orth DN (1979a) Epidermal growth factor (urogastrone) in human tissues. J Clin Endocrinol Metab 48:667–672
Hirata Y, Orth DN (1979b) Epidermal growth factor (urogastrone) in human fluids: size heterogeneity. J Clin Endocrinol Metab 48:673–679
Hirata Y, Moore GW, Bertagna C, Orth DN (1980) Plasma concentration of immunoreactive human epidermal growth factor (urogastrone) in man. J Clin Endocrinol Metab 50:440–447
Hunter T (1984) The epidermal growth factor receptor gene and its product. Nature 311:414–416
Kasselberg AG, Orth DN, Gray ME, Stahlman MT (1985) Immunocytochemical localization of human epidermal growth factor/urogastrone in several human tissues. J Histochem Cytochem 33:315–322
Maniatis T, Fritsch EF, Sambrook J (1984) Molecular cloning: a laboratory manual, 8th edn. Cold Spring Harbor Laboratory, New York, pp 187–210
Noorden S, Heitz P, Kasper M, Pearse AGE (1977) Mouse epidermal growth factor: light and electron microscopical localization by immunocytochemical staining. Histochemistry 52:329–340
Pesonen K, Viinikka L, Koskimies A, Banks AR, Nicolson M, Perheentupa J (1987) Size heterogeneity of epidermal growth factor in human body fluids. Life Sci 40:2489–2494
Stahlman MT, Orth DN, Gray ME (1989) Immunohistochemical localization of epidermal growth factor in the developing human respiratory system and in acute and chronic lung disease in the neonate. Lab Invest 60:539–547
Starkey RH, Orth DN (1977) Radioimmunoassay of human epidermal growth factor (urogastrone). J Clin Endocrinol Metab 45:1144–1153
Starkey RH, Cohen S, Orth DN (1975) Epidermal growth factor: identification of a new hormone in human urine. Science 189:800–803
Tahara E, Sumiyoshi H, Hata J, Yasui W, Taniyama K, Hayashi T, Nagae S, Sakamoto S (1986) Human epidermal growth factor in gastric carcinoma as a biologic marker of high malignancy. Jpn J Cancer Res 77:145–152
Ullrich A, Coussens L, Hayflik JS, Dull TJ, Gray A, Tam AW, Lee J, Yarden Y, Liberman TA, Schlessinger J, Downward J, Mayes ELV, Whittle N, Waterfield MD, Seeburg PH (1984) Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature 309:418–425
Ushiro H, Cohen S (1984) Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A431 cell membranes. J Biol Chem 255:8363–8365
Yasui W, Hata J, Yokozaki H, Nakatani H, Ochiai A, Ito H, Tahara E (1988a) Interaction between epidermal growth factor and its receptor in progression of human gastric carcinoma. Int J Cancer 41:211–217
Yasui W, Sumiyoshi H, Hata J, Kameda T, Ochiai A, Ito H, Tahara E (1988b) Expression of epidermal growth factor receptor in human gastric and colonic carcinomas. Cancer Res 48:137–141
Yasui W, Sumiyoshi H, Oda N, Miyamori S, Kameda T, Takekura N, Takanashi A, Tahara E (1988 c) Interaction between epidermal growth factor and gastrin on DNA synthesis of the gastrointestinal mucosa in rats. Hiroshima J Med Sci 37:1–6
Yeh YC, Scheving LE (1981) Circadian phase dependent effect of epidermal growth factor on deoxyribonucleic acid synthesis in ten different organs of the adult male mouse. Endocrinology 109:644–651
Yoshida K, Kyo E, Tsujino T, Sano T, Niimoto M, Tahara E (1990) Expression of epidermal growth factor, transforming growth factor-α and their receptor genes in human gastric carcinomas: Implication for autocrine growth. Jpn J Cancer Res 81:43–51
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Kajikawa, K., Yasui, W., Sumiyoshi, H. et al. Expression of epidermal growth factor in human tissues. Vichows Archiv A Pathol Anat 418, 27–32 (1991). https://doi.org/10.1007/BF01600241
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DOI: https://doi.org/10.1007/BF01600241