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 expression of ras, c-myc and c-erbB-2 oncoproteins in 100 human (73 ductal and 27 lobular) breast carcinomas has been examined using an immunohistochemical analysis. The monoclonal antibody Y13 259 has been used for the ras p21, the monoclonal antibody Myc1-9E10 for the c-myc p62 and the polyclonal antibody pAb1 (from Triton Bioscience Inc.) for the c-erbB-2 p185 oncoproteins. The following conclusions can be drawn from the analysis: Of the 100 breast carcinoma cases studied only 14 did not express any of the three oncogenes. The remaining 86 were positive for one or more of the three oncoproteins. Ductal carcinomas expressed oncoproteins in 92% of the cases (67/73), whereas lobular carcinomas expressed them in 70% of the cases (19/27). The most frequently expressed was c-myc p62 in 70% of cases followed by ras p21, 55% and c-erbB-2, 35%. Elevated expression of ras, myc or erbB-2 oncogenes did not correlate with the presence of metastasis in auxiliary lymph nodes, the numbers of infiltrated lymph nodes the grade of the tumor or hormone status. However, there appears to be a correlation between increased ras staining intensity and patient's age, below 50 years.
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PMID:ras, c-myc and c-erbB-2 oncoproteins in human breast cancer. 257 23

The structural interaction of the epidermal growth factor (EGF) receptor and the cytoskeleton of A431 cells has been studied using a monoclonal anti-EGF receptor antibody. This has been done with immunogold labeling using a variety of electron microscopical preparation procedures and EGF binding studies. By providing an image of the membrane-associated cytoskeleton, the dry cleavage method reveals a preferential localization of EGF receptors superimposed upon cytoskeletal filaments. The colocalization of gold particles with cytoskeletal filaments is not affected when pre-labeled cells are extracted with the non-ionic detergent Triton X-100, as visualized by dry cleavage. Using surface replication, this treatment results in visualization of the cytoskeleton. In these latter preparations, it is also observed that EGF receptor-coupled gold particles remain associated with cytoskeletal elements. Moreover, Triton extraction performed before immunogold labeling of EGF receptors demonstrates that isolated cytoskeletons contained binding sites for anti-EGF receptor antibodies. Using stereo micrographs of replica's obtained from these isolated cytoskeletons, it is shown that gold-labeled EGF receptors are exclusively present on the cortical membrane-associated region of the cytoskeleton and not on more intracellular-located filaments. Scatchard analysis of EGF binding to cells fixed with glutaraldehyde and treated with Triton X-100 before and after EGF binding indicates that a high affinity EGF binding site is associated with the Triton X-100 insoluble cytoskeleton.
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PMID:Epidermal growth factor receptors associated to cytoskeletal elements of epidermoid carcinoma (A431) cells. 301 1

Previous reports have shown that the epidermal growth factor (EGF) receptor is associated with the detergent-insoluble actin cytoskeleton. To assess how this association can influence receptor function, EGF-stimulated protein-tyrosine kinase activity was examined in the detergent-soluble and -insoluble (cytoskeletal) fractions of human A431 epidermoid carcinoma cells. EGF receptor extraction was optimal using 0.15% Triton X-100, and higher detergent concentrations did not significantly increase the amount of solubilized receptor as assessed by immunoblotting. Normalization of EGF-stimulated tyrosine kinase activity on the basis of receptor mass revealed that the specific activity of the cytoskeletal (0.15% Triton-insoluble) fraction is nearly 3-fold greater than that of the soluble receptor when using angiotensin II as the peptide substrate. The increased specific activity of the Triton-insoluble receptor suggests that interaction with the cytoskeleton can facilitate maximal kinase activity. This hypothesis is supported by the observation that, when compared with the soluble EGF receptor, the receptor in the cytoskeletal fraction demonstrates a 15-fold more favorable apparent Michaelis-Menten constant for ATP and a 4-fold more favorable Michaelis-Menten constant for angiotensin II. Although the cytoskeletal EGF receptor seems to represent less than 10% of the total receptor mass in cells not exposed to EGF, these data indicate that it comprises a highly active receptor pool. To examine the regulation of receptor association with the detergent-insoluble fraction, A431 cells were treated at 37 C with EGF for up to 5 h, or with the phorbol ester 12-phorbol 12-myristate 13-acetate for 1 h, and total receptor mass and distribution were determined. In these studies, total immunodetectable receptor decreased significantly after 20 min of EGF administration, whereas the population of Triton-insoluble receptors increased within 40 min to greater than four times that observed before EGF addition and remained at that level for the full 5 h of EGF treatment. Conversely, 12-phorbol 12-myristate 13-acetate treatment, which is known to down-regulate high affinity EGF binding, had little effect on receptor association with the cytoskeletal fraction. In sum, these data indicate the presence of a highly active subpopulation of cytoskeletally associated EGF receptors that can be up-regulated during long-term (5 h) ligand exposure.
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PMID:Modulation of epidermal growth factor receptor interaction with the detergent-insoluble cytoskeleton and its effects on receptor tyrosine kinase activity. 772 Jun 69

Using a serum enzyme immunoassay (EIA) kit from Triton diagnostics we detected c-erbB-2 oncoprotein activity in random sera containing highly elevated tumor markers and also in serial specimens from cancer patients expressing elevated oncoprotein activities. Elevated oncoprotein activity was found not only in sera of breast and ovarian carcinomas but also in sera from colorectal, pancreatic, and prostate carcinomas and even from primary hepatoma. Whenever oncoprotein was overexpressed in an individual patient, there was usually an excellent correlation between the oncoprotein activity and the level of dominant tumor marker in serial serum specimens. Based on the size exclusion S-200 column chromatography, we found only a single molecule containing c-erbB-2 oncoprotein activity in pooled sera from cancer patients whereas two oncoproteins slightly different in size were detected in breast tumor tissue cytosol. Using HPLC on a Superose 12 HR column, the serum portion of the oncoprotein was eluted at a position near IgG, suggesting that the extracellular domain of the oncoprotein exists as a dimer in the serum.
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PMID:Detection of the extracellular domain of c-erbB-2 oncoprotein in sera from patients with various carcinomas: correlation with tumor markers. 809 3

The ligand-stimulated tyrosine kinase activity of the normal human epidermal growth factor (EGF) receptor and a truncated EGF receptor lacking 164 carboxy-terminal (C-terminal) amino acids was examined in intact cells and after Triton X-100 extraction into Triton-soluble and -insoluble (cytoskeletal) preparations. Detergent extraction of the intact and truncated receptors appeared complete using 0.3% Triton as demonstrated by anti-EGF receptor immunoblots, tyrosine kinase assays, and marker enzyme (alkaline phosphatase) solubilization. Higher Triton concentrations yielded no additional EGF receptor extraction and began to inhibit EGF-stimulated kinase activity toward angiotensin II (AII). Furthermore, the tyrosine kinase activity of the truncated EGF receptor exhibited increased sensitivity to Triton extraction, suggesting a lower affinity or a more labile association of this receptor with the cytoskeleton. However, both EGF receptor forms had altered catalytic activity when associated with the cytoskeletal fraction, as evidenced by the increased phosphorylation of the exogenous substrates: AII, src-peptide, and [Val5]AII. Kinetic analyses of both receptor types revealed that the cytoskeletal fractions obtained using 0.3% Triton contain EGF receptor activity that exhibits a Michaelis-Menten constant (Km) for AII that is 2- to 3-fold more favorable than that calculated for the soluble receptor forms. EGF treatment of intact cells containing either the intact or truncated receptor revealed similar phosphorylated proteins in the soluble fraction of both cell types, although there was evidence for the enhanced phosphorylation of certain proteins (e.g. 115 and 50 kilodalton proteins) in cells containing the truncated receptor. There was also a greater number of tyrosine-phosphorylated proteins in the Triton-insoluble fraction of cells containing the truncated receptor, suggesting an altered specificity of this receptor toward selected cytoskeletal proteins. This work indicates that EGF receptor-cytoskeletal interaction may be an important consideration in the control of receptor-kinase activity and has examined the detergent sensitivity of this association. These studies also suggest that the C-terminal domain of the EGF receptor may affect cytoskeletal interaction in addition to influencing the receptor's catalytic capacity.
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PMID:Evidence for the potentiation of epidermal growth factor receptor tyrosine kinase activity by association with the detergent-insoluble cellular cytoskeleton: analysis of intact and carboxy-terminally truncated receptors. 824 11

We have studied by immunohistochemistry the nuclear expression of p53 and the finding of oncoprotein c-erbB-2 in a series of 85 breast carcinomas. The tissue was fixed in buffered formalin and embedded in paraffin. The primary antisera were obtained from Biogenex (USA), Bp53-12, monoclonal, used in a dilution of 1:100 for p53 and from Triton Diagnostics (USA), pAB-1, polyclonal, used in a dilution of 1:200 for c-erbB2. The detection system was the Vectastain Elite kit obtained from Vector Laboratories (USA). The results were compared with several morphological features of the tumors such as size and type of the tumor, extension of the intraductal component, nuclear grade, axillary lymph node metastasis and estrogen receptor data as well as with total and disease free survival. The oncoprotein p53 was detected in the nuclei in 25 (29.4%) of our cases (Fig 1). Its presence was correlated with tumor size (p < 0.01), high nuclear grade (p < 0.0001) and estrogen receptor negative tumors (p < 0.0001). There was an inverse relationship between p53 expression and 5 year disease free survival (p < 0.005). In 21 (24.7%) of the cases we found amplification of c-erbB-2. The staining pattern was membranous (Fig. 2). It was correlated significantly with the ductal type of invasive carcinoma (p < 0.05), an associated extensive intraductal component (p < 0.001), estrogen receptor negative tumors (p < 0.0001) and shortening of disease free survival in the patients with positive axillary lymph nodes (p < 0.005). In 9 cases we found staining for both markers without statistically significant relationship with the other features studied. We conclude that the presence of these genetic alterations demonstrated by immunohistochemistry were, in our series, unfavourable prognostic factors in invasive breast cancer.
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PMID:[Immunohistochemical analysis of p53 and c-erbB-2 in breast cancer]. 872 71