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Department of Medical Oncology, The Dr. Daniel den Hoed Cancer Center P.O. Box 5201, 3008 AE Rotterdam, The Netherlands.
Department of Division of Endocrine Oncology, and Department of Statistics, The Dr. Daniel den Hoed Cancer Center P.O. Box 5201, 3008 AE Rotterdam, The Netherlands.
Correspondence: Address requests for reprints and all correspondence to: Dr. J. G. M. Klijn, M.D., Ph.D., Division Endocrine Oncology, Dr. Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
Abstract
I. Introduction: EPIDERMAL growth factor (EGF) is a 53-aminoacid polypeptide (mol wt 6.045 K) that can influence proliferation and differentiation of a wide variety of cells (1–6). EGF as well as transforming growth factor-
(TGF-
), both of which can activate EGF receptor (EGF-R), are probably produced locally in many tissues as local growth factors rather than as systemic hormones. There is evidence that EGF plays a role in carcinogenesis and that the EGF-stimulated growth regulatory system (apart from that of benign cells) is also involved in proliferation of malignant cells (3). Cellular events are induced by EGF via its cell membrane receptor (EGF-R). The EGF-R is a 170 K glycoprotein that can be divided into an extracellular domain binding EGF or TGF-
, a short transmembrane domain, and an intracellular domain carrying tyrosine kinase activity (7). This intracellular domain shows close sequence homology with the c-erbB-2 and with neu (8), the rat homolog of c-erbB-2 oncogene. Increased expression of the EGF-R gene has been found in a variety of tumors, generally indicating a more aggressive behavior of cancers compared to those with low or normal expression (9–10) although this association is not invariant (11). EGF-R has been identified by several methods including radioligand binding assays, autoradiography, immunocytohistochemistry, immunoenzymatic assays, and measurement of EGF-R transcripts.
Footnotes
* Supported by Grant RRTI 88-9 from the Dutch Cancer Society.
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