Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rat neu proto-oncogene, which is a putative growth factor receptor closely related to the epidermal growth factor receptor, can be activated in vivo by a single point mutation in the sequence encoding its transmembrane region. The human homologue of neu, c-erbB-2, can be activated in vitro to an oncogenic form by point mutations in the same relative position in the gene. We have sought the presence of such activating mutations in a series of 100 cases of human breast cancer by polymerase chain reaction amplification and sequence-specific oligonucleotide hybridization, and also by a designed restriction fragment length polymorphism strategy in cases with Southern blot evidence of c-erbB-2 amplification. No evidence of activating point mutations in the c-erbB-2 protooncogene was found in any of these cases.
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PMID:Absence of activating transmembrane mutations in the c-erbB-2 proto-oncogene in human breast cancer. 218 82

The neu gene in rat neuro/glioblastoma was found to be activated by a single point mutation in the DNA sequence encoding the transmembrane region of the neu-encoded p185 protein. The human homologue of the rat neu gene, termed c-erbB-2 or HER-2, can also be activated in vitro by a similar mutation in the corresponding region. Although the human neu gene was shown to be amplified/overexpressed in a large portion of human breast and ovarian cancer, no reports indicate that the human neu gene is activated by a point mutation in human tumor. To study the possible point mutation of neu gene in human tumors, we characterized the genomic structure in the transmembrane region of human neu gene, which in turn allowed us to determine DNA sequence in this region directly following DNA amplification by polymerase chain reaction. We analyzed 7 tumor cell lines (2 breast cancer, 1 neuroblastoma, 1 rhabdomyosarcoma, and 3 glioma) and 11 tumor tissue samples (8 breast and 3 ovarian cancers). No mutation was found in the transmembrane region of human neu gene. Our results suggest that unlike the rat neuro/glioblastoma, the single point mutation in the transmembrane region of the human neu gene is a rare event in human tumors. In this study, we developed a technique for direct DNA sequencing of the transmembrane region of the human neu gene. This technique makes it possible to screen a large number of tumor samples.
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PMID:Direct sequencing analysis of transmembrane region of human Neu gene by polymerase chain reaction. 220 83

Treatment of intact cells with media containing high concentrations of ionic and non-ionic solutes induced increased tyrosine phosphorylation of the epidermal growth factor (EGF) receptor and the protein product of the erbB-2/neu proto-oncogene. This self phosphorylation occurred in the absence of EGF or other growth factors. High concentrations of solutes did not activate phosphorylation of either isolated EGF receptor or EGF receptor solubilized by non-ionic detergents. No evidence for receptor dimerization was found in response to hyperosmotic shock. Since receptor dimers have been implicated in the EGF-induced activation of EGF receptor, hyperosmotic shock may activate EGF receptor by a different mechanism.
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PMID:Ligand-independent tyrosine phosphorylation of EGF receptor and the erbB-2/neu proto-oncogene product is induced by hyperosmotic shock. 246 83

The neu (c-erbB-2) gene encodes a transmembrane protein with tyrosine kinase activity that appears to be a growth factor receptor. Antibody was generated by immunization of rabbits with a synthetic polypeptide that was based on an internal sequence at the carboxy terminus of the molecule. This antibody was used to survey the expression of neu in human skin by immunohistochemistry. Significant protein was found in the squamous cell layer of the surface epidermis, in squamous cell carcinomas, in the external root sheath of hair follicles, and in eccrine gland secretory cells; it was poorly expressed in the basal cell layer and in a basal cell carcinomas. Increased neu expression appears to be associated with the differentiation of keratinocytes.
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PMID:Distribution of neu (c-erbB-2) protein in human skin. 247 Aug 27

Activation of the epidermal growth factor (EGF) receptor kinase leads to autophosphorylation and to the phosphorylation of various cellular substrates. The three known autophosphorylation sites of EGF receptor are located at the carboxyl-terminal tail where they probably act to compete with and thus modulate substrate phosphorylation. Mutational analysis and microsequencing techniques have been used to localize and identify new autophosphorylation site(s) of the EGF receptor. We have compared the phosphopeptide maps of human EGF receptor, and two deletion mutants lacking 63 and 126 amino acids from the carboxyl-terminal tail with the phosphopeptide maps of HER/neu and a chimeric EGF receptor containing the carboxyl-terminal tail of HER2/neu. HER2/neu is highly homologous to the EGF receptor, and it probably functions as a growth factor receptor for as yet unidentified growth factor. On the basis of this analysis, we have concluded that all autophosphorylation sites of EGF receptor and HER2/neu are located in their carboxyl-terminal tails. Utilizing the EGF receptors with carboxyl-terminal deletions, we were also able to identify tyr1086 as an additional autophosphorylation site of EGF receptor. Direct microsequencing of a phosphorylated tryptic peptide from the human EGF receptor confirmed this assignment.
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PMID:All autophosphorylation sites of epidermal growth factor (EGF) receptor and HER2/neu are located in their carboxyl-terminal tails. Identification of a novel site in EGF receptor. 254 78

To examine a potential contribution of protooncogene abnormalities other than point-mutational activation of the K-ras protooncogene in the classification of non-small cell lung cancer, amplification of cellular protooncogenes was studied in 47 lung tumour specimens obtained at thoracotomy and in four lung tumour cell lines. The primary tumours included 21 adenocarcinomas, nine large-cell carcinomas, 13 epidermoid carcinomas, one carcinoid and three metastases of primaries outside the lung. The copy numbers per haploid genome of 11 protooncogenes in every tumour sample were determined: H-ras, K-ras, N-ras, c-myc, N-myc, L-myc, erbB, mos, myb, ncu (erbB-2) and ral amplifications. The c-myc gene was amplified 5-7-fold in two adenocarcinomas, the H-ras gene 3 5-fold in one adenocarcinoma, while the K-ras and the neu gene were amplified in lung metastases from a colorectal and a breast cancer primary respectively. None of the tumours with an amplified protooncogene simultaneously harboured a mutationally activated K-ras gene. We conclude that amplification of the investigated protooncogenes is a rare event in non-small cell lung cancer. In view of the two c-myc amplifications detected, a systematic study of c-myc expression levels in non-small cell lung cancers appears worthwhile.
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PMID:Cellular protoonocogenes are infrequently amplified in untreated non-small cell lung cancer. 254 15

The neu gene (also called NGL, erbB-2, and HER-2) encodes a 185-190 kDa transmembrane glycoprotein, p185neu, which has tyrosine-specific kinase activity and is homologous to but distinct from the epidermal growth factor receptor. The normal expression of neu mRNA and protein has been demonstrated in epithelial tissues of adult animals. Also, activation of the neu oncogene has been implicated in a variety of human adenocarcinomas. In the present study, we examined the expression of the p185neu protein in normal and transformed digestive tract tissues and in a panel of digestive tract-derived cell lines. By immunohistochemistry, strong reactivity was observed in the mucosal epithelium of the stomach, small intestine, and colon of both rodents and humans. In the small intestine, there was prominent p185neu expression by mucosal epithelium of the villus, with little or no staining in the crypts. Prominent expression was observed in the liver parenchyma, the endocrine and exocrine portions of the pancreas, and in the salivary gland. Immunoreactive p185neu was also demonstrated in fetal human intestinal epithelium. Tissue sections of selected benign and malignant colonic neoplasms were also examined. Immunoreactivity was consistently greater in adenomatous polyps than in adjacent normal colonic epithelium or areas showing malignant degeneration. By radioimmunoprecipitation, there was decreased expression in cell lines derived from more anaplastic colonic tumors. The p185neu protein is expressed widely in normal and transformed epithelial tissues of the digestive tract of the adult rat and human. This finding suggests that p185neu, a putative growth factor receptor, may play a role in the regulation of normal growth and function or in the malignant transformation of these cells.
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PMID:Expression pattern of the neu (NGL) gene-encoded growth factor receptor protein (p185neu) in normal and transformed epithelial tissues of the digestive tract. 256 77

To determine whether the amplification of the proto-neu oncogene (also called c-erbB-2) plays a role in tumorigenicity, we previously generated an NIH 3T3 transfectant (DHFR/G-8) that carried the amplified proto-neu gene. The DHFR/G-8 cells exhibited normal morphology. Their growth curve was similar to that of NIH 3T3 cells but was different from that of the B104-1 cell, and NIH 3T3 transfectant that carries the activated neu oncogene. When injected into nude mice, B104-1 cells produced tumors within 2 weeks, whereas the DHFR/G-8 cells did not produce tumors until 3 months after injection, and the NIH 3T3 cells did not produce any tumors even after 3 months. The tumors produced by the injection of the DHFR/G-8 cells were excised and grown in culture. The cells derived from the tumors were of transformed morphology and highly tumorigenic. The DNAs from the tumor cells were transfected into NIH 3T3 cells. The transfection resulted in foci on the NIH 3T3 monolayer. Southern analysis indicated that the foci derived from the transfection contained the neu gene. Using oligonucleotides as probes, the neu gene in the foci was found to carry a single-point mutation identical to the one previously found in the rat neuroblastoma and glioblastoma induced by the ethylnitrosourea. We conclude that the DNA region encoding the transmembrane domain of neu is a hot spot for converting the proto-neu gene into an activated oncogene and that amplification of the proto-neu gene facilitates mutation of the hot spot.
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PMID:Amplification of the proto-neu oncogene facilitates oncogenic activation by a single point mutation. 256 34

The neu gene was first identified in rat tumors that had been induced by the carcinogen ethyl nitrosourea. The human homolog of neu, usually designated c-erbB-2, is located on chromosome 17, q21. It specifies a transmembrane receptor-like phosphoglycoprotein that is closely related to the EGFr (c-erbB-1). The ligand for c-erbB-2 is not known. A significant proportion of adenocarcinomas (especially of the breast, colon, and pancreas) have amplification and/or overexpression of c-erbB-2. The unique qualities associated with the subset of tumors that overexpress c-erbB-2 have not yet been firmly identified.
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PMID:The neu (c-erbB-2) oncogene. 256 4

We have investigated the biological function of an unidentified human growth factor, the ligand of the putative HER2 receptor, by characterizing the signalling properties of its receptor. HER2 (or c-erbB-2), the human homolog of the rat neu proto-oncogene, encodes a transmembrane glycoprotein of the tyrosine kinase family that appears to play an important role in human breast carcinoma. Since a potential ligand for HER2 has not yet been identified, it has been difficult to analyze the biochemical properties and biological function of this cell surface protein. For this reason, we replaced the HER2 extracellular domain with the closely related ligand binding domain sequences of the epidermal growth factor (EGF) receptor, and examined the ligand-induced biological signalling potential of this chimeric HER1-2 protein. This HER1-2 receptor is targetted to the cell surface of transfected NIH 3T3 cells, forms high and low affinity binding sites, and generates normal mitogenic and cell transforming signals upon interaction with EGF or TGF alpha. The constitutive activation of wild-type HER2 in transfected NIH 3T3 cells suggests the possibility that these cells synthesize the as yet unidentified HER2 ligand and activate HER2 by an autocrine mechanism.
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PMID:HER2 cytoplasmic domain generates normal mitogenic and transforming signals in a chimeric receptor. 256 8


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