Increased EGF receptors on human squamous carcinoma cell lines

Summary A method to determine the binding of epidermal growth factor (EGF) to the particulate fraction of the cell has been established and evaluated using rat liver, human placenta, and tumours of human breast and brain. Little EGF receptor (EGFR) activity was detected in normal or benign tumour tissues except for meningioma (positive in 95% samples), but EGFR were present in 43% of 131 breast tumours and 75% of 55 primary cerebral tumours. Despite the strong inverse correlation between EGFR activity and oestrogen receptors in breast tumours and a tendency for high levels of EGFR activity to be associated with glioblastoma multiforme, analysis showed that EGFR was of little prognostic significance in patients with tumours of either breast or brain.

mentioning

confidence: 99%

Epidermal growth factor receptors in intracranial and breast tumours: their clinical significance

Hawkins

Killen²,

Whittle³

et al. 1991

“…Owing to its reported overexpression, the EGFR has been suggested to be a potential target for diagnosis (Soo et al, 1987;Divgi et al, 1991) or directed therapy of SCC (Harris, 1990;Ennis et al, 1991). Although several studies have indicated that the EGFR is overexpressed on human SCC, quantitation of the overexpression relies heavily on the study of SCC-derived cell lines in which the frequency of significant overexpression is very high (Cowley et al, , 1986. Most studies have relied upon cell lines which have been isolated under culture conditions unfavourable for the growth of normal keratinocytes (Easty et al, 1981).…”

mentioning

confidence: 99%

“…The EGFR is frequently, but not necessarily, overexpressed on SCC-derived cell lines (Wrann & Fox, 1979;Merlino et al., Cowley et al, 1984Cowley et al, , 1986Ozanne et al, 1986a;Prime et al, 1994) and tumours (Hendler & Ozanne, 1984;Gullick et al, 1986;Ozanne et al, 1986b;Derynck et al, 1987;Hendler et al, 1989;Ishitoya et al, 1989;Weichselbaum et al, 1989;Gullick, 1991;Gorgolis et al, 1992). Its gene, c-erbB (Downward et al, 1984), is located on chromosome 7pl2-14 and spans at least 10kb (Haley et al, 1987).…”

mentioning

confidence: 99%

Epidermal growth factor receptor expression by human squamous cell carcinomas of the head and neck, cell lines and xenografts

Stanton

Richards²,

Reeves³

et al. 1994

“…Many human cancers of epithelial origin express high numbers of EGF receptors and are stimulated by activation of the receptor via a transforming growth factor-α (TGF-α)/EGF receptor autocrine loop (Ozanne et al, 1986;Cowley et al, 1986;Ishitoya et al, 1989;Hendler and Ozanne, 1984). The increased receptor levels are associated with poor clinical prognosis in patients with cancers of the bladder (Neal et al, 1985), breast , and lung (Veale et al, 1987) and others.…”

mentioning

confidence: 99%

True

2000

The receptor for epidermal growth factor (EGF) is a transmembrane glycoprotein with intrinsic tyrosine kinase activity (Ullrich and Schlessinger, 1990). Many human cancers of epithelial origin express high numbers of EGF receptors and are stimulated by activation of the receptor via a transforming growth factor-α (TGF-α)/EGF receptor autocrine loop (Ozanne et al, 1986;Cowley et al, 1986;Ishitoya et al, 1989;Hendler and Ozanne, 1984). The increased receptor levels are associated with poor clinical prognosis in patients with cancers of the bladder (Neal et al, 1985), breast , and lung (Veale et al, 1987) and others. Blockade of EGF receptor as an approach for anticancer therapy has been extensively studied over the past decade (Fan and Mendelsohn, 1998).Monoclonal antibody (mAb) 225 binds to EGF receptor with an affinity similar to that of the natural ligands EGF and TGF-α, competes with these natural ligands for receptor binding, and inhibits ligand-induced activation of the receptor tyrosine kinase (Sato et al, 1983;Gill et al, 1984). This antibody, along with other EGF receptor-blocking mAbs, inhibits the proliferation of a variety of cultured and xenografted tumour cell lines that are stimulated by the TGF-α/EGF receptor autocrine loop, including cell lines derived from cancers of the vulva (Fan et al, 1993a;1994), breast (Ennis et al, 1989), prostate (Peng et al, 1996;Hofer et al, 1991), ovary (Ye et al, 1999), bladder (Perrotte et al, 1999), kidney (Prewett et al, 1998), lung (Lee et al, 1992), colon (Karnes et al, 1992;Wu et al, 1996), brain (Wersall et al, 1997), and head and neck (Modjtahedi et al, 1993). It has been postulated that these antibodies inhibit tumour cell proliferation by an antibody-mediated interruption of the autocrine activation of EGF receptors in cancer cells (Van de Vijver et al, 1991;Fan et al, 1993b;Baselga et al, 1996). The antibody-mediated growth inhibition in most malignant cell lines has been attributed primarily to a reduced proliferation rate with an increased cell population in G1 phase of the cell cycle (Fan et al, 1997;Wu et al, 1996;Peng et al, 1996). In nonmalignant epithelial cells there was a prominent cytostatic effect with complete G1 arrest (Stampfer et al, 1993;Chou et al, 1999).DiFi colon cancer cells are unique in that exposure of these cells to mAb 225 resulted in not only G1 phase arrest of cell cycle, with a concomitant increase in the level of p27 Kip1 and a decrease in CDK activity, but also subsequent cell death through apoptosis (Wu et al, 1995;. When nude mice bearing well-established subcutaneous DiFi cell xenografts were treated with mAb 225, the tumour was completely eradicated, a result not normally seen with other cancer cells stimulated by the TGF-α/EGF receptor autocrine pathway (Masui et al, 1991). The EGF receptor gene in these cells was not found to be rearranged or genetically altered, but the gene was found to be amplified in the range of 60-80 copies per cell, which is approximately twice the copy number SummaryWe previously reported that e...