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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An embryonal carcinoma cell line, P19S18, was transfected with the rat oncogene neu to investigate the function of its protein product, p185*, in a multipotential cellular environment. Levels of message for p185* were determined by in situ hybridization analysis and two highly expressing clones, PnnA and PnnB, were isolated. As demonstrated by indirect immunofluorescence and immunoprecipitation, these neu-transfected cells synthesized a full length rat p185*. The transfectants do not resemble typical embryonal carcinoma cells either before or after differentiation is induced by retinoic acid treatment. They are much larger, flatter, "epithelioid" cells. These cells have lost the expression of stage specific embryonic antigen-1 (SSEA-1), but do synthesize and assemble the basement membrane components laminin and fibronectin. These results suggest that expression of the neu oncogene in a multipotential cell line may induce the synthesis of proteins indicative of an epithelioid phenotype due to the presence of p185*.
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PMID:Transfection of murine P19S18 embryonal carcinoma cells with the oncogene neu induces an epithelioid phenotype. 136 18

We have observed a heterogeneity in the ability of a monolayer of cultured rat astrocytes to support the attachment and growth of dissociated embryonic hypothalamic neurons in culture. Areas of the monolayer which have an uneven surface ('rocky' astrocytes) are poor substrates for neuronal attachment and neuritic outgrowth, while surrounding areas of the glial monolayer ('flat' astrocytes) support extensive neuronal growth. Astrocytes obtained from both neonatal cerebral cortex or hypothalamus displayed 'rocky' morphology. We utilized immunocytochemical techniques with antibodies directed against putative adhesion molecules to investigate the source of this heterogeneity. Antibodies against tenascin/cytotacin, fibronectin, laminin, N-CAM, thrombospondin, heparan sulfate proteoglycan, and the p185 protein product of the neu oncogene were employed in indirect-immunofluorescence experiments. We found that the difference in the surface properties of astrocytes appears to be correlated with the expression of the extracellular matrix molecule tenascin/cytotacin, but not with any of the other molecules we tested. Our data suggest that tenascin/cytotactin is inhibitory to neuronal attachment and process outgrowth in the developing nervous system.
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PMID:Astrocyte topography and tenascin cytotactin expression: correlation with the ability to support neuritic outgrowth. 169 75

Serum-free mouse embryo cells, cultured in basal nutrient medium supplemented with insulin, transferrin, epidermal growth factor, fibronectin, and high-density lipoprotein, do not exhibit growth crisis, lack detectable chromosomal aberrations, are nontumorigenic in vivo, are dependent on epidermal growth factor for survival, and are growth inhibited by serum or platelet-free plasma. These cells after transfection with the human Ha-ras or rat neu oncogenes no longer required epidermal growth factor for survival, were tumorigenic in vivo, and also proliferated in serum-containing medium. Autocrine activity capable of replacing epidermal growth factor was detected in conditioned medium from ras-transformed cultures, but little such activity was detected in medium from neu-transformed cultures. In addition, the capability of ras or neu-transformed cells to grow in serum-containing medium could not be mimicked in untransformed cells by the addition of growth factors or conditioned medium from transformed cells. These results suggest that the known structural similarity of the neu gene product to the EGF receptor is also reflected in a functional similarity by which the mutationally activated neu protein can replace the ligand-activated EGF receptor. These results also suggest that the ability of ras- and neu-transformed cells to escape the effect of the inhibitory serum activity is a nonautocrine property distinct from the acquisition of EGF autonomy.
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PMID:ras and neu oncogenes reverse serum inhibition and epidermal growth factor dependence of serum-free mouse embryo cells. 197 70

We studied the differential response of oncogene transformed NIH3T3 cells to glucocorticoids. As demonstrated for transformed human fibroblasts, the morphology of neu-, ras-, src- and sis-transformed mouse fibroblasts became more normal after glucocorticoid treatment. This change was not due to inhibition of the expression of oncogene mRNA or protein. However, the abl-transformed NIH3T3 cells were resistant to glucocorticoid-induced morphology change. These results indicate that the glucocorticoid-induced morphology change is specific to certain oncogene-transformed NIH3T3 cells. Transformed human fibroblasts generally have reduced amounts of cell surface fibronectin. When treated with glucocorticoids, they incorporate higher levels of fibronectin in their extracellular matrix, which correlates with their change in morphology. However, we found that, except for abl-transformed cells, the fibronectin level of the other oncogene transformed mouse cells was similar to non-transformed cells. Moreover, treatment of the neu-, ras-, src- and sis-transformed cells with glucocorticoids resulted in a change in morphology but no increase in cell surface fibronectin. These studies demonstrate that the glucocorticoid-induced morphological change of oncogene-transformed NIH3T3 cells is not due to enhanced expression of fibronectin. Therefore, other mechanisms are responsible for this glucocorticoid-induced phenotypic change of oncogene-transformed cells.
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PMID:Effect of glucocorticoids on oncogene transformed NIH3T3 cells. 218 73

We have immortalized rat central nervous system (CNS) cells of primary cultures of rat optic nerve with murine leukemia virus psi-2,SV-40-6, which is defective in assembly and contains the SV-40 large T antigen and neomycin resistance genes, to produce a cell line that we named A7. After drug selection, greater than 90% of the growing cells expressed nuclear SV-40 large T cells and a fraction of these contained the astrocyte-specific marker, glial fibrillary acidic protein. The majority of these cells also expressed surface marker A4 (specific for neural tube derivatives), Ran 2, p185 (the 185-kD phosphoprotein product of the neu oncogene), and fibronectin, but did not express the astrocyte enzymes glutamine synthetase and monoamine oxidase B. Surface markers characteristic of glial progenitors (A2B5) and oligodendrocytes (galactocerebroside) were not detected. After two rounds of cell cloning, subclone A7.6-3 expressed Ran 2, fibronectin, and the neural cell adhesion molecule (N-CAM) but not glial fibrillary acidic protein and A4. The A7 cell line and subclones also displayed certain functions of type 1 astrocytes: the conditioned medium of these cells had a potent mitogenic activity for glial progenitor cells which could be neutralized by anti-platelet-derived growth factor antibodies and monolayers of these cells supported the growth of embryonic hypothalamic neurons. We conclude that a retrovirus containing SV-40 large T antigen can immortalize rat CNS cells and that such immortalized glial cells retain at least two important functions of type 1 astrocytes: the ability to secrete platelet-derived growth factor and to support the growth of embryonic CNS neurons. Moreover, such stable immortalized clonal cell lines can be used to study gene regulation in glial cells.
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PMID:Antigenic and functional characterization of a rat central nervous system-derived cell line immortalized by a retroviral vector. 305 37

The multimodular glycoprotein tenascin-C is transiently expressed, predominantly by glial cells, during the development of the central and peripheral nervous systems. This extracellular matrix glycoprotein is involved in the control of cell adhesion, neuron migration and neurite outgrowth. Distinct functional properties for neuronal cell types have been attributed to separate tenascin-C domains using antibody perturbation studies and in vitro experiments on tenascin-C fragments. In order to study potential roles of tenascin-C for glial cell biology, a library of recombinant tenascin-C domains was used in a bioassay in vitro. Embryonic day 14 astrocytes, various astroglial-derived cell lines (C6, A7 and Neu7) and oligodendroglial-derived cell types (Oli-neu and G26-20) were examined in an adhesion assay and compared to the neuroblastoma cell line N2A. A binding site for most cell types, except for A7 and N2A, could be assigned to the first three fibronectin type III domains. Repulsive properties could be mapped to three different sites the epidermal growth factor-like repeats, fibronectin type III repeats 4 and 5 and to the alternatively spliced region of the molecule. The responses to these repulsive sites varied according to the cell type. These data are consistent with the interpretation that different cell types express distinct sets of tenascin-C receptors which might regulate cellular responses via distinct second messenger pathways.
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PMID:Glial cell interactions with tenascin-C: adhesion and repulsion to different tenascin-C domains is cell type related. 884 7

DSD-1-PG is a chondroitin sulfate proteoglycan with neurite-outgrowth promoting properties expressed during development and upon lesion of neural tissues which has been defined with the specific monoclonal antibody 473HD. Double immunofluorescence studies performed on primary cerebellar cultures document that the proteoglycan is expressed on the surface of immature glial cells and the neural cell line Oli-neu, a model of mouse oligodendrocyte progenitors. Biochemical and immunoprecipitation studies performed with biosynthetically labelled Oli-neu and primary neural cells demonstrated that DSD-1-PG is expressed in vitro as a proteoglycan of 1000 kD apparent Mr with two core glycoproteins of 250 kD and 400 kD. In order to study the regulation of DSD-1-PG expression, an in vitro enzyme-linked immunosorbent assay based on Oli-neu and mAb 473HD was established. TGF-beta1-3 induced up-regulation of the proteoglycan, while various growth factors and cytokines did not significantly affect DSD-1-PG expression in both the supernatant and the extract of the culture monolayer. FACSCAN analysis suggested that the proteoglycan is upregulated on the surface of Oli-neu. Cell substrate adhesion assays revealed that this enhanced expression correlates with a selective reduction of adhesion to laminin, but not fibronectin or merosin, which could specifically be neutralized by antibodies to DSD-1-PG. We conclude that the proteoglycan contributes to the regulation of glial precursor interactions with the extracellular matrix.
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PMID:Expression of DSD-1-PG in primary neural and glial-derived cell line cultures, upregulation by TGF-beta, and implications for cell-substrate interactions of the glial cell line Oli-neu. 960 Mar 79

The effects of all-trans retinoic acid (ATRA) and epidermal growth factor (EGF) on the expression of nm23-H1, a metastasis suppressor gene, were studied in a human 7721 hepatocarcinoma cell line. It was discovered that the expression of nm23-H1 mRNA was up-regulated by ATRA. This was compatible with the observation that the metastasis-associated phenotypes, such as chemotaxic cell migration and invasion, were both reduced in the ATRA-treated and nm23-H1-cDNA-transferred 7721 cells. However, ability of cells to adhere to fibronectin and laminin was not altered identically in the ATRA-treated and nm23-H1-cDNA-transfected 7721 cells. In contrast, the expression of nm23-H1 mRNA in 7721 cells was down-regulated both by the treatment with EGF and by the transfection of c-erbB-2/neu cDNA, which codes a protein homologous to the EGF receptor. EGF is a compound with biological effects opposite to those of ATRA, and c-erbB-2/neu is known to be a metastasis-promoting gene. These results reveal that the metastasis-preventing effect of ATRA may partly result from the up-regulation of nm23-H1, and the metastasis-promoting effects of EGF and c-erbB-2/neu were probably mediated in part by the down-regulation of nm23-H1.
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PMID:Effects of all-trans retinoic acid and epidermal growth factor on the expression of nm23-H1 in human hepatocarcinoma cells. 1066 47

The pCMV4 plasmid containing the cancer-promoting gene, c-erbB2/neu, was cotransfected into the human hepatocarcinoma cell line 7721 with the pcDNA3 vector, which contains the 'neo' selectable marker. Several clones showing stable expression of c-erbB2/neu were established and characterized by determination of c-erbB2/neu mRNA and its encoded protein p185. Expression of Lewis antigens and alpha1,3-fucosyltransferases and the biological behavior of 7721 cells after c-erbB2/neu transfection were studied using mock cells transfected with the vectors pCMV4 and pcDNA3 as controls. SLe(x) expression on the surface of mock cells was high, whereas expression of SDLe(x), Lex and SLe(a) was absent or negligible. This is compatible with the abundant expression of alpha1,3-fucosyltransferase VII, very low expression of alphafucosyltransferase III/VI, and almost absent expression of alpha1,3-fucosyltransferase IV in the mock cells. After transfection of c-erbB2/neu, expression of SLe(x) and alpha1,3-fucosyltransferase VII were simultaneously elevated, but that of alphafucosyltransferase III/VI was not altered. The expression of both SLe(x) and alpha1,3-fucosyltransferase VII correlated positively with the expression of c-erbB2/neu in different clones, being highest in clone 13, medium in clone 6, and lowest in clone 7. In addition, the adhesion of 7721 cells to human umbilical vein endothelial cells (HUVECs) or P-selectin, as well as cell migration and invasion, were increased in c-erbB2/neu-transfected cells. These increases also correlated positively with the expression intensities of c-erbB2/neu, SLe(x) and alpha1,3-fucosyltransferase VII in the different clones, whereas cell adhesion to fibronectin correlated negatively with these variables. mAbs to SLe(x) (KM93) and SDLe(x) (FH6) significantly and slightly, respectively, abolished cell adhesion to HUVECs or P-selectin and cell migration and invasion. mAbs to SDLe(x) and SLe(a) did not suppress cell adhesion to HUVECs nor inhibit cell migration and invasion. Transfection of alpha1,3-fucosyltransferase VII cDNA into 7721 cells showed similar results to transfection of c-erbB2/neu, and the increased adhesion to HUVECs, cell migration, and invasion were also inhibited significantly by KM93 and slightly by FH6. These results indicate that expression of alpha1,3-fucosyltransferase VII and its specific product, SLe(x), and their capacity for cell adhesion, migration and invasion are closely related. Therefore, the c-erbB2/neu gene is proposed to be a metastasis-promoting gene, and its effects are at least partially mediated by the increased expression of alpha1,3-fucosyltransferase VII and SLe(x).
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PMID:Transfection of the c-erbB2/neu gene upregulates the expression of sialyl Lewis X, alpha1,3-fucosyltransferase VII, and metastatic potential in a human hepatocarcinoma cell line. 1142 80

The lysyl oxidase (LOX) gene encodes an enzyme (LOX) critical for extracellular matrix maturation. The LOX gene has also been shown to inhibit the transforming activity of Ras oncogene signaling. In particular, the pro-peptide domain (LOX-PP) released from the secreted precursor protein (Pro-LOX) was found to inhibit the transformed phenotype of breast, lung, and pancreatic cancer cells. However, the mechanisms of action of LOX-PP remained to be determined. Here, the ability of LOX-PP to attenuate the integrin signaling pathway, which leads to phosphorylation of focal adhesion kinase (FAK), and the activation of its downstream target p130Cas, was determined. In NF639 breast cancer cells driven by Her-2/neu, which signals via Ras, ectopic Pro-LOX and LOX-PP expression inhibited fibronectin-stimulated protein tyrosine phosphorylation. Importantly, phosphorylation of FAK on Tyr-397 and Tyr-576, and p130Cas were substantially reduced. The amount of endogenous p130Cas in the Triton X-100-insoluble protein fraction, and fibronectin-activated haptotaxis were decreased. Interestingly, expression of mature LOX enzyme enhanced fibronectin-stimulated integrin signaling. Of note, treatment with recombinant LOX-PP selectively reduced fibronectin-mediated haptotaxis of NF639, MDA-MB-231, and Hs578T breast cancer cells. Thus, evidence is provided that one mechanism of action of LOX-PP tumor suppression is to block fibronectin-stimulated signaling and cell migration.
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PMID:The lysyl oxidase pro-peptide attenuates fibronectin-mediated activation of focal adhesion kinase and p130Cas in breast cancer cells. 1902 90


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