Disease relevance of Genes, erbB-1

• This study describes genomic rearrangements near the 3' end of the epidermal growth factor receptor (EGFR) gene in eight glioblastomas displaying coamplification and expression of both normal and rearranged EGFR [1].
• Using recombinant retroviruses, we have examined the effects of signalling-incompetent EGF-R mutants on the growth-promoting and transforming potential of ligand-activated, overexpressed wild-type EGF-R and the v-erbB oncogene product [2].
• Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in non-small cell lung cancer specimens from patients responding to anilinoquinazoline EGFR inhibitors [3].
• Xenografts from eight malignant human gliomas were established in athymic mice and were used to study amplification and expression of the epidermal growth factor receptor (EGFR) gene [4].
• The DiFi colorectal carcinoma cell line, derived from a patient with familial adenomatous polyposis, was examined for gene expression and production of the autocrine growth factor transforming growth factor alpha (TGF-alpha) and for epidermal growth factor receptor (EGFR) gene expression and gene copy number [5].

High impact information on Genes, erbB-1

• The epidermal growth factor receptor (EGFR) gene is frequently amplified and/or overexpressed in human malignancies [6].
• The v-erbB gene product of avian erythroblastosis virus (AEV) has extensive homology with the receptor for epidermal growth factor (EGF) [7].
• The v-erbB gene of avian erythroblastosis virus (AEV) codes for an integral plasma membrane glycoprotein, gp74erbB [8].
• The epidermal growth factor receptor (EGFR) gene is amplified or mutated in 30%-50% of human gliobastoma multiforme (GBM) [9].
• These seven viruses contained v-erbB genes encoding the complete C terminus of the EGFR [10].

Chemical compound and disease context of Genes, erbB-1

• PURPOSE: Recent studies reported that clinical responsiveness to gefitinib was associated with somatic mutation of epidermal growth factor receptor (EGFR) gene in non-small cell lung cancers (NSCLC) [11].
• Somatically acquired mutations in the epidermal growth factor receptor (EGFR) gene in lung cancer are associated with significant clinical responses to gefitinib, a tyrosine kinase inhibitor that targets EGFR [12].
• OBJECTIVE: We sought to determine whether hydroxyurea could accelerate the loss of amplified epidermal growth factor receptor (EGFR) genes from glioblastoma multiforme (GBM) [13].
• Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancers are associated with increased sensitivity of these cancers to drugs that inhibit EGFR kinase activity such as gefitinib and erlotinib [14].

Biological context of Genes, erbB-1

• Because the wa-2 mutation was mapped previously to the vicinity of the EGF/TGF-alpha receptor (EGFR) gene on mouse chromosome 11, we hypothesized that the wa-2 phenotype might result from a defect in either the expression or activity of EGFR, or both [15].
• Alterations of the epidermal growth factor receptor (EGFR) gene are common in some forms of cancer and the most frequent is a deletion of exons 2-7 [16].
• The Rous-associated virus 1 env gene, which encodes the envelope gp85 and gp37 glycoproteins, was isolated and inserted in place of the v-erbB oncogene into an avian erythroblastosis virus-based vector, carrying the neo resistance gene substituted for the v-erbA oncogene, to generate the pNEA recombinant vector [17].
• Our molecular genetic studies have suggested that adult GBM can be divided into two genetic subsets: tumors with p53 tumor suppressor gene mutations and chromosome 17p loss that occur more commonly in younger patients; and tumors with epidermal growth factor receptor (EGFR) gene amplification that occur more commonly in older patients [18].
• Loss of heterozygosity (LOH) for chromosome arms 9p, 10p, 10q, and 17p and amplification of the epidermal growth factor receptor (EGFR) gene have been identified as frequent genetic changes in malignant astrocytomas [19].

Anatomical context of Genes, erbB-1

• Correspondence re: S. Shintani et al., Intragenic mutation analysis of the human epidermal growth factor receptor (EGFR) gene in malignant human oral keratinocytes. Cancer Res., 59: 4142-4147, 1999 [20].
• These results demonstrate the existence of EGF receptors in the prepubertal female rat hypothalamus and suggest that changes in EGFR gene expression and biologically active EGFR protein contributes to the neuroendocrine process underlying the first preovulatory surge of gonadotropins.(ABSTRACT TRUNCATED AT 250 WORDS)[21]
• All-transretinoic acid (retinoid) had little effect on EGF-R, v-erbB gene expression and the proliferation of PSS fibroblasts [22].

Associations of Genes, erbB-1 with chemical compounds

• By three criteria--tunicamycin inhibition, lectin binding and metabolic labeling with radioactive sugar precursors--the product of the v-erbB gene appears to be a glycoprotein [23].
• Expression of the human epidermal growth factor receptor (EGFR) gene is inhibited by ligand-activated thyroid hormone receptor (T3R) [24].
• In contrast, CEF expressing either the v-myc, v-myb-ets, v-mil, v-sea or v-erbB oncogenes are still sensitive to retinoic acid [25].
• First, individualizing second-line chemotherapy could optimize its effect; the discovery of dramatic responses and significant improvement in survival in patients with epidermal growth factor receptor (EGFR) gene mutations who are treated with EGFR tyrosine kinase inhibitors may lead to the application of other novel therapeutic approaches [26].
• Sequencing of the mutant v-erbB gene revealed a single amino acid change of a histidine to an aspartate residue at a position equivalent to amino-acid 826 of the human epidermal growth factor receptor [27].

Gene context of Genes, erbB-1

• It has been previously reported that epidermal growth factor receptor (EGFR) gene amplification and TP53 mutation correlate with the response to RT in patients with glioblastoma [28].
• Transfection of an epidermal growth factor receptor (EGFR) gene was used to generate a subline that was conditionally transformed (colony formation in soft agar was dependent on transforming growth factor alpha). v-raf transfection was used to generate constitutive transformation [29].
• PURPOSE: To study the structure and expression of the cyclin D1 and the epidermal growth factor receptor (EGFR) genes in a cohort of 298 non-small-cell lung cancer (NSCLC) specimens [30].
• Unlike the product of the v-erbB oncogene, which is a truncated version of the EGF receptor, the glycoprotein encoded by the v-fms oncogene retains an intact extracellular ligand-binding domain so that cells transformed by v-fms express CSF-1 receptors at their surface [31].
• Other growth factor-related gene polymorphisms include the cytochrome P450c17alpha enzyme (CYP17) gene MspA I C/T polymorphism at the 5'-UTR promoter region, the epidermal growth factor receptor (EGFR) gene Bsr I polymorphism (A to T) at position 2,073, and the insulin-like growth factor-2 (IGF-2) gene Apa I A/G at exon 9 [32].

Analytical, diagnostic and therapeutic context of Genes, erbB-1

• We find that differential PCR is able to detect amplification of the HER2 (c-erbB-2) and the epidermal growth factor receptor (EGFR) genes and can be used to arrive at a semiquantitative estimate of gene dosage [33].
• Human malignant gliomas contain epidermal growth factor receptor (EGFR) gene mutations that encode tumor-associated antigens (TAAs) that can be targeted using immunological techniques [34].
• We describe a rapid, formamide-free, random oligomer-enhanced in situ hybridization method in formalin-fixed, paraffin-embedded tissue sections using a biotinylated oligonucleotide probe for colorimetric detection of the mRNA transcript of the epidermal growth factor receptor (EGFR) gene, a putative protooncogene [35].

References