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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We explored the mechanism of antigrowth action of Curcumin by investigating its effect on epidermal growth factor (EGF) receptor intrinsic kinase activity in the human epidermoid carcinoma A431 cells. The short-term treatment of cells with Curcumin inhibited EGF receptor intrinsic kinase activity up to 90% in a dose- and time-dependent manner, and also inhibited EGF-induced tyrosine phosphorylation of EGF receptors. The observed early effects of Curcumin were mediated via a cellular mechanism(s), and preceded the period when inhibition of cell growth occurred.
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PMID:Inhibitory effect of curcumin on epidermal growth factor receptor kinase activity in A431 cells. 780 21

Although human squamous cell carcinoma (SCC) cell lines frequently contain an elevated number of epidermal growth factor (EGF) receptor accompanied with amplification of EGF receptor/c-erbB gene, it is well known that EGF inhibits the growth of these cells in culture at doses that stimulate the growth of epidermal keratinocytes and dermal fibroblasts. To study this growth inhibitory effect of EGF on the SCC cell lines, 3H-thymidine incorporation into DNA and cell cycle distribution were analyzed. In HSC-1 and NA cells, which contain the highest number of EGF receptor among these SCC cell lines, the inhibition of 3H-thymidine incorporation was apparent 2 to 4 hours after treatment with 100 ng/ml of EGF and reached more than 95% inhibition after 24 hours. Two-color cell cycle analysis using fluorescein isothiocyanate (FITC)-conjugated anti-Bromodeoxyuridine (BrdU) antibody and propidium iodide revealed that this inhibitory effect was due to cell cycle arrest not only in G1 but also in G2 phase. This effect was well correlated to the sensitivity to the growth inhibitory effect of EGF among the 4 SCC cell lines. These observations suggest that the SCC cells contain altered machineries which regulate the normal cell growth in both G1 and G2 phases, and the EGF affects these machineries via overexpressed its receptor.
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PMID:[Cell cycle arrest induced by epidermal growth factor on human squamous cell carcinoma cell lines]. 780 40

Among the tissue, cellular, and molecular changes which take place during the development of squamous cell carcinoma (SCC) of the upper aerodigestive tract, only a limited number can be used as surrogate endpoint biomarkers (SEBs) in cancer chemoprevention trials. Molecular SEBs will be genes or gene products which can be measured accurately and reliably, are altered in intraepithelial neoplasia (dysplasia), correlate strongly with the true outcome (invasive cancer), and are modulated by a chemoprevention agent(s). To identify and modulate molecular SEBs in intraepithelial neoplasia of the upper aerodigestive tract, we studied expression of the epidermal growth factor receptor (EGFR), transforming growth factor-alpha (TGF-alpha), and HER-2/neu genes in oral leukoplakia before, during, and after treatment with 13-cis-retinoic acid, a vitamin A derivative. Four of nine patients treated for 3 months with 1 mg/kg/day of 13-cis-retinoic acid had complete resolution of their leukoplakia. Biopsies were taken of leukoplakia and adjacent normal-appearing mucosa before, during, and after treatment. Immunohistochemistry was performed using the BioGenex Super Sensitive Biotin-Streptavidin horseradish peroxidase detection system. Pretreatment expression of EGFR, TGF-alpha, and HER-2/neu in leukoplakia was increased when compared to normal-appearing mucosa. TGF-alpha expression decreased during treatment in leukoplakia, but not in normal-appearing mucosa, suggesting that TGF-alpha may serve as an intermediate endpoint in cancer chemoprevention trials.
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PMID:Retinoid modulation of biomarkers in oral leukoplakia/dysplasia. 782

The histopathological characteristics, proto-oncogene amplification, immunohistopathology of the c-erbB-2 product distribution, and the DNA content of nuclei were examined in metastatic brain tumors, which consisted of seven adenocarcinomas, a large cell carcinoma, a squamous cell carcinoma, a renal cell carcinoma and a mucoepidermoid carcinoma. A very high incidence of DNA changes was seen in these tumors. Proto-oncogene amplification and abnormal DNA content in the nuclear portion were found in 64% (7/11) and 67% (6/9) of cases, respectively. We also found double oncogene alteration in three cases metastasizing from lung, esophagus and kidney, and triple oncogene alteration in one case metastasizing from breast. We could not identify the common alterations in the group of metastatic brain tumor cells. These data suggest that the proto-oncogene amplifications and the alteration of DNA ploidy pattern may contribute to the metastatic process.
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PMID:DNA amplifications and elevated expression of proto-oncogene in addition to altered DNA ploidy in metastatic brain tumors. 791 69

The epidermal growth factor (EGF) receptor is overexpressed in squamous cell carcinoma and the EGF receptor has been proposed as a potential target for new therapeutic agents in this tumour type. We have utilized a tyrphostintype inhibitor of the EGF receptor tyrosine kinase domain (RG50864) to study EGF-dependent proliferation and phosphorylation in two human squamous cell carcinoma cell lines. There were selected on the basis that whereas both cell lines have a large number of EGF receptors, one is growth inhibited by EGF (A431) while the proliferation of the other cell line (B2A4) is stimulated by EGF. EGF induced receptor autophosphorylation in each of the two cell lines; however, the level of phosphorylation was greater in the A431 cells than in the B2A4 cells. The pattern of proteins phosphorylated in response to EGF was different in the two squamous cell lines. RG50864 antagonized the EGF-dependent proliferation of B2A4 cells, but was unable to reverse the inhibitory effect of EGF on A431 cell growth. RG50864 partially inhibited EGF receptor autophosphorylation in both cell lines and completely inhibited the EGF-dependent phosphorylation of other cellular proteins, one of which co-migrated with MAP2kinase in both cell lines. Moreover, different dose-response relationships for the inhibition of phosphorylation of various proteins were observed in A431 versus B2A4 cells. As a substrate competitive inhibitor of the EGF receptor tyrosine kinase, the primary mode of action of RG50864 may be to prevent the association and/or phosphorylation of multiple specific substrates of the receptor in a fashion which may be cell line dependent. The precise relationship of these phosphorylation events to tyrphostin sensitivity remains to be established.
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PMID:Alterations in EGF-dependent proliferative and phosphorylation events in squamous cell carcinoma cell lines by a tyrosine kinase inhibitor. 791 99

We examined effect of the tyrosine kinase inhibitor herbimycin A on A431 human epidermoid carcinoma cells which over-express epidermal growth factor (EGF) receptor. Herbimycin A inhibited the autophosphorylation of EGF-stimulated receptors in intact cells both time- and dose-dependently. The inhibition was found to be due to a decrease in the level of expression of the receptor amount, because herbimycin A equally decreased the receptor quantity and EGF-stimulated receptor kinase activity in intact cells, but did not exhibit a direct inhibitory effect on EGF receptor kinase activity in vitro. The decrease of the level of EGF receptor was also confirmed by 125I-EGF binding to herbimycin A-treated cells, and Scatchard analysis showed that the decrease in the receptor number occurred in the major population of the low-affinity binding ones, whereas the number with high-affinity binding was unaffected. Interestingly, although the proliferation of A431 cells was inhibited by EGF, herbimycin A converted EGF into a stimulatory ligand for cell growth, as determined by both cell number and DNA synthesis. These findings indicated that herbimycin A decreased the level of expression of EGF receptor by a mechanism other than inactivation of the receptor kinase and reversed the transformed phenotype of A431 cells to a normal one in the proliferative response to EGF.
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PMID:Conversion of epidermal growth factor (EGF) into a stimulatory ligand for A431-cell growth by herbimycin A by decreasing the level of expression of EGF receptor. 803 91

The effect of herbimycin A on the biosynthesis of epidermal growth factor (EGF) receptor was examined in human epidermoid carcinoma A431 cells. Cells were pulse-labelled with [35S]methionine, and EGF receptor biosynthesis was quantified by immunoprecipitation using a monoclonal anti-(EGF receptor) antibody. In the presence of herbimycin A, an immature 160 kDa EGF receptor precursor accumulated in 1 h and disappeared completely in 4 h. Pulse-labelled 160 kDa receptor precursor in the absence of herbimycin A, however, was converted normally into a 170 kDa one by chase with herbimycin A. Herbimycin A affected neither the synthesis of the secreted form of EGF receptor devoid of cytoplasmic domain, nor that of the transferrin receptor in A431 cells. The herbimycin A-induced degradation of 160 kDa EGF receptor precursor was not inhibited by an inhibitor of lysosomal enzymes, NH4Cl. Endoglycosidase H digestion of the 160 kDa precursor converted it into the deglycosylated 130 kDa precursor peptide. These results suggested that herbimycin A selectively acted on the EGF receptor precursor during the synthesis of the 160 kDa form, probably on the cytoplasmic domain, to form an aberrant molecule which was subjected to rapid degradation in the endoplasmic reticulum.
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PMID:Accelerated degradation of 160 kDa epidermal growth factor (EGF) receptor precursor by the tyrosine kinase inhibitor herbimycin A in the endoplasmic reticulum of A431 human epidermoid carcinoma cells. 803 92

A small molecule called PD 153035 inhibited the epidermal growth factor (EGF) receptor tyrosine kinase with a 5-pM inhibition constant. The inhibitor was specific for the EGF receptor tyrosine kinase and inhibited other purified tyrosine kinases only at micromolar or higher concentrations. PD 153035 rapidly suppressed autophosphorylation of the EGF receptor at low nanomolar concentrations in fibroblasts or in human epidermoid carcinoma cells and selectively blocked EGF-mediated cellular processes including mitogenesis, early gene expression, and oncogenic transformation. PD 153035 demonstrates an increase in potency over that of other tyrosine kinase inhibitors of four to five orders of magnitude for inhibition of isolated EGF receptor tyrosine kinase and three to four orders of magnitude for inhibition of cellular phosphorylation.
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PMID:A specific inhibitor of the epidermal growth factor receptor tyrosine kinase. 806 47

The mRNA expression of transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGFR), c-erbB-2 and c-met proto-oncogenes in eight newly established cell lines and 29 primary tumors of human non-small-cell lung carcinoma (NSCLC) have been investigated. In vitro, the expressions of TGF-alpha, c-erbB-2, and c-met were consistently high in adenocarcinomas, while EGFR was expressed highest in a squamous cell carcinoma cell line. There was linear correlation between the levels of expression of TGF-alpha and EGFR or c-erbB-2, and between EGFR and c-erbB-2. The c-met expression was also correlated with those of TGF-alpha, EGFR, and c-erbB-2. In vivo, The mean mRNA levels of TGF-alpha, EGFR, and c-met, but not c-erbB-2, were higher in carcinomas than in normal lung tissues (2.8, 1.7, and 3.0 times, respectively); however, only adenocarcinomas expressed a significantly higher level of c-erbB-2 than their corresponding normal tissues (2.2 times). In 20 patients whose paired normal and tumor tissue were examined, the percentage of cases with greater than twofold increase in expression in carcinomas than normal were 55% for both TGF-alpha and EGFR, 30% for c-erbB-2, and 47% for c-met. Among the histological subtypes of NSCLC, a higher percentage of adenocarcinomas than squamous cell carcinomas over-expressed these genes, especially c-erbB-2 and c-met. Over-expression is rarely the result of gene amplification. The results suggest a differential expression of growth factor and receptor genes among the various histological subtypes of NSCLCs.
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PMID:In vitro and in vivo expressions of transforming growth factor-alpha and tyrosine kinase receptors in human non-small-cell lung carcinomas. 809 69

The demonstration that alpha-sialic acid is the minimal determinant recognized by human reovirus is compatible with the finding that this virus binds to multiple sialoglycoproteins on the host cell surface. However, the identities of these proteins have remained unknown. By applying detergent-solubilized plasma membranes from the human epidermoid carcinoma A431 cell line to immobilized reovirions, we have identified the 150- to 170-kDa epidermal growth factor (EGF) receptor as one of the cell surface proteins recognized by reovirus. Direct interaction between the N-terminal extracellular domain of the EGF receptor and reovirus was confirmed by the demonstration that of a number of proteins secreted by A431 cells, the 105-kDa N-terminal cell surface domain of the EGF receptor was the major protein recognized by the virus. However, as expected, reovirus and EGF did not compete for the same binding site on the EGF receptor of intact A431 cells.
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PMID:Recognition of the epidermal growth factor receptor by reovirus. 821 75


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