Epidermal growth factor receptors

Abstract

EGF-Rs are cell membrane glycoproteins of wide distribution. They have not yet been fully characterized or purified but are probably molecules of 170-190,000 mol. wt. in most cells. The growth factor EGF binds and will saturate cell surface receptors with a KA of about 5 X 10(9) M-1 although a receptor class with an affinity in excess of 10(10) M-1 has been detected in some cells. The number of receptors on a cell does not determine the level of its response. Some cell types have receptors which bind EGF, but with no mitogenic response. The ways in which receptor affinity and/or number is modulated are described. This and other evidence is reviewed in a search for a suitable model of a mechanism of action on the cell, which best fits the current data. There is ample evidence that EGF binds to the receptor; that ligand-receptor complexes cluster or aggregate; and then are internalized and degraded, but evidence for a direct connection between internalization and the subsequent mitogenic response is lacking. Good correlations between internalization and mitogenic responses have been observed and developed into a theory of endocytic activation, but there is a body of evidence which cannot be accommodated by this theory. Instead, an alternative model is suggested.

Increased EGF receptors on human squamous carcinoma cell lines

“…Epidermal growth factor (EGF) is a polypeptide of 6,045 daltons which has been shown to be mitogenic to both ectodermal cells (Cohen & Elliot, 1963;Carpenter & Cohen, 1979;Gospodarowicz, 1981) and endodermal cells (Konturek et al, 1981) in vivo and which promotes growth of mesodermal and ectodermal cells in vitro (Cohen & Elliot, 1963;Gospodarowicz et al, 1978;Adamson & Rees, 1981;Rheinwald & Green, 1977). The physiological effects of EGF on human epidermal cells, however, are not clearly delinated, but appear to be potentially involved in both growth and differentiation .…”

“…In addition to its in vivo and in vitro effect on the proliferation of skin and keratinocytes where it also retards differentiation, (Carpenter & Cohen, 1979;Rheinwald & Green, 1977) epidermal growth factor appears to play an important role in the development and regulation of a wide range of human malignancies including glial tumours (Libermann et al, 1985) bladder tumours breast carcinomas (Filmus et al, 1985;Fitzpatrick et al, 1984) and epidermoid malignancies (Fabricant et al, 1977;Cowley et al, 1984;Ozanne et al, 1985). In previous reports we have briefly reported the presence of increased levels of EGF receptors in a number of cell lines derived from squamous cell carcinomas of the head and neck Ozanne et al, 1985).…”

EGFR Mutation and Tyrosine-Kinase Inhibitors (TKI) in Non Small Cell Lung Cancer: An Overview

“…It is essential for the normal development of various tissues such as bone [7] , mammary ducts [8] and vascular system [9] . Owing to its role in development, EGFR is normally found at low levels in most of the tissues where it is regulated both transcriptionally and mechanically by existing as an inactive monomer, requiring dimerization that is facilitated by the binding of extracellular signals such as Epidermal Growth Factor (EGF) [10][11] The epidermal growth factor receptor (EGFR) cascades the signaling pathway that regulates tumor-cell proliferation, invasion, angiogenesis, metastasis, and apoptosis. EGFR plays a central role in lung carcinogenesis.…”

Precise mapping of the EGF receptor gene on the human chromosome 7p12 using an improved fish technique

“…It is localized on the membrane surface of various types of mammalian cells including human cells (Adamson and Rees, 1981;Behzadian et aL, 1982;Damjanov et al, 1986). EGFR is expressed generally in proliferating cells and its expression ceases when the cells achieve terminal differentiation .…”