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)

An antibiotic, azatyrosine [L-beta-(5-hydroxy-2-pyridyl) alanine], specifically converts ras-, raf- or c-erbB2 (neu)-transformed NIH3T3 cells to apparently normal phenotype. The reversion induced by azatyrosine is permanent, and the phenotype of the revertant cells does not change even after prolonged culture in the absence of azatyrosine [N. Shindo-Okada, O. Manabe, H. Nagahara & S. Nishimura (1989). Mol. Carcinogen., 2, 159-167]. In the present study, we found that neurite outgrowth of PC12 cells induced by expression of either the ras or raf oncogenes was inhibited by addition of azatyrosine to the medium. Azatyrosine also inhibited neurite outgrowth induced by microinjection of oncogenic Ras protein into PC12 cells. The dose dependency was much the same for the two systems, inhibition of neurite outgrowth of PC12 cells and reversion of the transformed NIH3T3 cells. Microinjection of azatyrosine into the cells was as effective as addition to the medium, indicating that the target of azatyrosine is intracellular. In contrast, neurite outgrowth induced by nerve growth factor, which has been shown to be mediated by normal Ras [N. Hagag, S. Halegouna & M. Viola (1986). Nature, 319, 680-682], was found to be resistant to azatyrosine. Azatyrosine also showed no effect on neurite outgrowth induced by a membrane-permeant cyclic AMP analog through another pathway. These findings suggest that azatyrosine sensitivity is the result of abnormal signal transduction by oncogenic Ras. It was shown that azatyrosine also inhibited differentiation-associated growth arrest of PC12 cells induced by oncogenic Ras. In Ras-induced neurite outgrowth, the azatyrosine-sensitive process was found to be completed in the first 6-9 h, and is probably essential for the commitment of PC12 cells to differentiation rather than to growth.
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PMID:Azatyrosine inhibits neurite outgrowth of PC12 cells induced by oncogenic Ras. 132 88

Using the rat sciatic nerve as a model for the study of Schwann cell differentiation we have identified a Schwann cell precursor, a distinct cell type present in developing nerves at a time when they are projecting to their target tissues. These cells develop into Schwann cells over a relatively short time in vivo. In vitro, they can generate Schwann cells if they are cultured in neuron-conditioned medium or in the presence of neu-differentiation factors (NDF) (neuregulins, heregulins, glial growth factor), a recently discovered family of growth factors expressed at high levels in neurons. Thus neu-differentiation factors may be important neuro-glia signalling molecules in the Schwann cell lineage. Later stages in the development of Schann cells, such as differentiation towards a myelin phenotype, can be studied using cultured Schwann cells. These cells dedifferentiate both in vivo and in vitro when they are deprived of axonal contact. Elevation of intracellular cyclic AMP levels in the absence of cell division causes high levels of expression of Po, the major myelin glycoprotein. TGF beta s and FGFs suppress this induction, while IGFs promote it.
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PMID:Development and differentiation of Schwann cells. 888 21

The biological effects of the growth-inhibiting epidermal pentapeptide, pyroGlu-Glu-Asp-Ser-GlyOH (EPP), were studied at cell and gene level. After treatment with high doses of EPP (1,000 ng/ml 2 nanomol/ml), 3H-TdR incorporation was reduced in both non-transformed (NC3H10) and transformed (TC3H10) cells. These findings were corroborated by flow cytometry DNA distributions that revealed that the fraction of cells with G1 DNA content was increased while the fraction of cells with S phase DNA content was reduced in both cell lines. In addition, a site-selective analogue of cyclic AMP (cAMP), 8-Br-cAMP, was found to inhibit proliferation of the two fibroblast cell lines, but the transformed cells were more sensitive to this agent. When both EPP and 8-Br-cAMP were given together to cultures of NC3H10 or TC3H10 cells the transformed TC3H10 cells were inhibited whilst there was no obvious effect on NC3H10 cell proliferation. The results of Northern blots showed that RNA expression of c-fos, ki-ras, and neu genes in TC3H10 cells decreased following treatment with EPP. The results could indicate that N-substituted growth-inhibiting oligopeptides may have an anti-tumor effect when combined with 8-Br-cAMP.
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PMID:The growth-inhibiting epidermal pentapeptide, pyroGlu-glu-asp-ser-GlyOH, inhibits growth and alters gene expression in non-transformed NC3H10 and transformed TC3H10 fibroblasts. 1002 19

It has been proposed that binding of ligand to the estrogen receptor (ER) releases its association with transcriptional corepressors, allowing the ER to recruit coactivators, which possess histone acetylase activity, and induce transcription of gene promoters containing estrogen response elements. It has also been proposed that the antiestrogen tamoxifen recruits transcriptional corepressors to the AF-2 region of the hormone-binding domain of the ER, thus blocking ER-mediated transcription. The ER cross-talks with a number of mitogenic signaling pathways and second messengers, like the epidermal growth factor receptor, the insulin-like growth factor-I receptor, mitogen-activated protein (MAP) kinase, phosphatidylinositol-3 kinase/Akt, dopamine, and cyclic AMP. Some of these molecules may: (a) support ligand-independent ER transcription; (b) increase the association of ER with coactivators of transcription; and/or (c) reduce the antiestrogen-induced association of ER with corepressors. These events either alone or in combination may result in hormone independence and/or antiestrogen resistance. We have examined whether signaling by HER2/neu (erbB-2) receptor tyrosine kinase, which can induce antiestrogen resistance, can also disrupt the tamoxifen-induced interaction of ER with transcriptional corepressors. Notably, tamoxifen-induced association of ER with the transcriptional corepressors N-CoR or SMRT was reduced in HER2-overexpressing breast tumor cells but not in cells with low HER2 levels. Small molecule inhibitors of the HER2 kinase or MAP extracellular signal-regulated kinase 1/2 or dominant-negative MAP extracellular signal-regulated kinase 1/2 constructs restored the inhibitory effect of tamoxifen on both ER-mediated transcription and tumor cell proliferation. Treatment with both tamoxifen and the small molecule HER1/2 kinase inhibitor AG1478 reduced mitogen-activated protein kinase activity and markedly reduced growth of established MCF-7/HER2 xenografts in athymic nude mice. Similar results have been obtained with ZD1839 ("Iressa"), an epidermal growth factor receptor (HER1) tyrosine kinase inhibitor. Taken together, these data suggest that exogenous inhibitors of the HER-signaling network and other mitogenic pathways can abrogate or delay the emergence of antiestrogen resistance, thus providing an evaluable therapeutic strategy in human breast carcinoma.
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PMID:Inhibition of erbB receptor (HER) tyrosine kinases as a strategy to abrogate antiestrogen resistance in human breast cancer. 1191 37