Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neu/HER-2 proto-oncogene (also called erbB-2) encodes a transmembrane glycoprotein related to the epidermal growth factor receptor. We have purified to homogeneity a 44 kd glycoprotein from the medium of ras-transformed cells that stimulates phosphorylation of the Neu protein and retains activity after elution from the polyacrylamide gel. The protein is active at picomolar concentrations and displays a novel N-terminal sequence. Cross-linking experiments with radiolabeled p44 result in specific labeling of Neu, indicating that p44 is a ligand for Neu or a related receptor. The purified protein induces phenotypic differentiation of cultured human breast cancer cells, including altered morphology and synthesis of milk components. This is accompanied by an increase in nuclear area, inhibition of cell growth (probably by cell cycle arrest at the late S or the G2/M phases), and induction of DNA polyploidy. We propose the name Neu differentiation factor (NDF) for p44.
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PMID:Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein that induces differentiation of mammary tumor cells. 134 15

c-erbB2/neu is a transforming oncogene that encodes a 185-kDa transmembrane glycoprotein. In many but not all studies, amplification and/or overexpression of the human c-erbB2/neu oncogene has been correlated with poor prognosis and the number of lymph node metastases in node-positive breast cancer patients. We have shown that expression of the activated rat c-erbB2/neu oncogene in mouse embryo fibroblast 3T3 cells is sufficient to induce experimental metastases in nude mice. Important steps in the metastatic event are tumor cell adhesion to endothelial cells and invasion of basement membranes. Therefore, we further examined the ability of c-erbB2/neu oncogene-transformed 3T3 cells to adhere to microvessel endothelial cells and secrete basement membrane-degradative enzymes. The c-erbB2/neu oncogene-transformed 3T3 cells were shown to be more adherent and have higher gelatinase activities. Since we had previously shown that the adenovirus 5 E1A gene product can suppress c-erbB2/neu-induced transformation of 3T3 cells, we examined the possibility that E1A can abrogate the metastatic properties of c-erbB2/neu-transformed 3T3 cells. We found that introduction of the E1A gene into c-erbB2/neu-transformed 3T3 cells reduced the formation of experimental metastatic tumors and inhibited metastasis-associated properties, such as adhesion to microvessel endothelial cells, migration through a layer of reconstituted basement membrane (Matrigel) and secretion of basement membrane-degradative enzymes. The results indicate that the mechanism by which the c-erbB2/neu gene induces higher metastatic potential is to promote adhesion and invasion steps of the metastatic cascade. The E1A gene, which functions by inhibiting these steps, is thus a suppressor gene for c-erbB2/neu-induced experimental metastasis.
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PMID:Mechanisms of c-erbB2/neu oncogene-induced metastasis and repression of metastatic properties by adenovirus 5 E1A gene products. 135 95

The human homolog of the rat neu oncogene, HER2 (also termed c-erbB2) has been demonstrated in amplified form in human breast tumors with poor prognosis. Although amplification of the gene correlates with expression of a 185-kDa transmembrane glycoprotein, no extensive information is available regarding the extent of tissue and tumor specificity of this gene product. We have addressed this issue by immunohistochemically evaluating the expression of p185 HER2 in normal tissue and various tumors using monoclonal antibodies (MAbs) to distinct epitopes of its extracellular domain. No detectable levels of p185 HER2 were found in fetal tissues analyzed, with the exception of renal tubules in 2 out of 3 specimens tested and in intestinal epithelium. In adult tissues, detectable levels of this glycoprotein were found in a restricted number of cell types, the expression being heterogeneous among individuals and cell histotypes. Among the neoplasms assayed p185 HER2 was expressed in 46% of primary breast cancers, in 28% of ovarian tumors and in 30% of colon rectum malignancies. No male breast adenocarcinomas were p185-positive. A large number of other tumors tested revealed only a low incidence of expression of the p185. In metastatic breast tumors p185 HER2 was demonstrated homogeneously among multiple autologous lesions and almost invariably (80%) the expression of p185 in the primary lesion correlated with that of the deriving metastases. Our findings indicate that the expression of the p185 HER2 represents a tumor marker of clinical relevance in breast cancer. Whether this holds true for other malignancies remains to be explored.
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PMID:Expression of the p185 encoded by HER2 oncogene in normal and transformed human tissues. 196 37

The neu oncogene encodes a 185,000 dalton transmembrane glycoprotein, p185. The current study examined the effects of p185-specific monoclonal antibody administration on the tumorigenic growth of neu-transformed NIH3T3 cells implanted into nude mice. Treatment with anti-p185 monoclonal antibodies of the IgG1, IgG2a, IgG2b subclasses was able to profoundly inhibit the growth of neu-transformed cells. Furthermore, while none of these antibodies individually was able to cause complete eradication of tumors, the administration of mixtures of antibodies reactive with two distinct regions on the p185 molecule resulted in synergistic anti-tumor effects and complete eradication of tumors in a substantial fraction of the treated animals. The effect was oncogene specific, since the growth of ras transformed cells was not influenced by anti p185 antibodies. These results demonstrate that antibodies reactive with multiple domains of a tumor antigen can exert synergistic anti-tumor effects, and suggest that therapy with monoclonal antibodies specific for the neu oncogene product may play a role in cancer treatment.
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PMID:Monoclonal antibodies reactive with distinct domains of the neu oncogene-encoded p185 molecule exert synergistic anti-tumor effects in vivo. 245 Dec

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

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

The neu oncogene (also referred to as c-erbB-2 and HER2) encodes a 185-kDa transmembrane glycoprotein with tyrosine kinase activity termed p185. The p185 glycoprotein is structurally related to the epidermal growth factor receptor. It is thought that p185 is the receptor for an as yet unidentified growth factor. In the present study, RNA blot analyses and immunohistochemical studies were performed on rat tissues obtained from a variety of prenatal and postnatal stages to examine the expression of the neu oncogene and its product, p185, during normal development. Expression of the neu gene was detected in mid-gestation embryos in a variety of tissues including nervous system, connective tissue, and secretory epithelium, but not in lymphoid tissue. In adult animals, secretory epithelial tissues and basal cells of the skin expressed neu. These studies demonstrate that the neu gene is expressed in a tissue- and developmental stage-specific manner. We suggest that the p185 molecule plays an important role in the growth and development of a variety of tissues, and, in particular, in epithelial tissue.
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PMID:Stage- and tissue-specific expression of the neu oncogene in rat development. 331 11

The neu oncogene encodes a 185-kDa transmembrane glycoprotein tumor antigen, termed p185. We have recently described a monoclonal antibody reactive with a cell surface domain of the p185 molecule. In vivo treatment with this anti-p185 monoclonal antibody was able to significantly inhibit the tumorigenic growth of neu-transformed NIH 3T3 cells implanted into nude mice. Such treatment had no effect on the tumorigenic growth of Ha-ras-transformed NIH 3T3 cells. Furthermore, anti-p185 antibody treatment was able to inhibit the growth of the rat neuroblastoma cells from which the neu oncogene was initially isolated. These results demonstrate that a monoclonal antibody reactive with the extracellular domain of an oncogene-encoded protein can exert a significant antitumor effect; such antibodies may prove useful in the therapy of certain malignancies.
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PMID:Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-encoded tumor antigen. 346 78

We have constructed a vaccinia virus recombinant that expresses the extracellular domain of the rat neu oncogene-encoded protein, a 185-kDa transmembrane glycoprotein termed p185. Strain NFS mice immunized with this recombinant virus developed a strong antibody response against the neu oncogene product and were fully protected against subsequent tumor challenge with neu-transformed NIH 3T3 cells. No tumor immunoprotection was found when recombinant virus-immunized mice were challenged with Ha-ras-transformed NIH 3T3 cells. These data indicate that immunization with a single oncogene-encoded antigen can fully and specifically protect animals against tumor cells bearing this antigen.
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PMID:Effective tumor immunotherapy directed against an oncogene-encoded product using a vaccinia virus vector. 347 12

HER2, the erbB-2/neu proto-oncogene product, is a 185-kDa transmembrane glycoprotein related to the epidermal growth factor receptor. Overexpression of HER2 was reported in several human adenocarcinomas, including mammary and ovarian carcinomas. A family of glycoproteins, the heregulin/neu differentiation factors, was characterized and implicated as the ligands for HER2. Recently, it has been shown that HER2 alone is not sufficient to reconstitute high affinity heregulin receptors and that HER3 or HER4 may be the required components of the heregulin receptors on mammary carcinoma cells (Sliwkowski, M.X., Schaefer, G., Akita, R.W., Lofgren, J.A., Fitzpatrick, V.D., Nuijens, A., Fendly, B.M., Cerione, R.A., Vandlen, R.L., and Carraway, K.L., III (1994) J. Biol. Chem. 269, 14661-14665; Plowman, G.D., Green, J.M., Culouscou, J.-M., Carlton, G.W., Rothwell, V.M., and Buckley, W. (1993) Nature 366, 473-475). Using the Cytosensor to measure the extracellular acidification rate, we have examined the effects of recombinant human heregulin-alpha on three mammary carcinoma cell lines expressing HER2 (MDA-MB-453, SK-BR-3, and MCF-7), an ovarian carcinoma cell line expressing HER2 (SK-OV-3), and CHO-K1 and 293-EBNA cells stably transfected with HER2. By reverse transcription polymerase chain reaction and Western blotting, we found that the breast cells also express HER3 and that the ovarian line co-expresses the HER4 message. A dramatic increase in the acidification rate was observed for the mammary carcinoma cells co-expressing high levels of HER2 and HER3. In contrast, the ovarian cells expressing high levels of HER2 and low levels of HER4 or CHO-K1 and 293-EBNA cells expressing HER2 alone were not responsive to heregulin. When these same transfected cells were exposed to monoclonal anti-HER2 antibody followed by anti-IgG to cause aggregation of the HER2 molecules, an increase in the acidification rate was observed, indicating coupling of transfected HER2 to the signal transduction pathway. Transfection of HER2 into MCF-7 cells, on the other hand, gave 4-fold enhanced acidification responses. These data, together with the previously reported high affinity heregulin binding and activation of tyrosine phosphorylation in HER2 and HER3 co-transfected cells support the role of HER2 and HER3 as components of the heregulin receptor in breast cells.
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PMID:Heregulin activation of extracellular acidification in mammary carcinoma cells is associated with expression of HER2 and HER3. 767 53


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