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

In order to analyze the correlation between immunohistochemical positivity for c-erbB-2 oncoprotein and prognosis in patients with malignant salivary gland tumors, 59 cases of malignant tumors of the major salivary glands, including 35 parotid gland, 20 submaxillary gland and 4 sublingual gland tumors, were studied immunohistochemically using a polyclonal antibody against c-erbB-2 oncoprotein. Positive staining was observed in 13 (22%) of the 59 cases. Interestingly, positive results were obtained only in adenocarcinoma (6/20) and carcinoma in pleomorphic adenoma (7/15), and not in any other histological types such as adenoid cystic carcinoma, mucoepidermoid tumor, and squamous cell carcinoma. There was no correlation between the degree of differentiation of adenocarcinoma and c-erbB-2 positivity. Since the carcinoma in pleomorphic adenoma positive for c-erbB-2 oncoprotein was adenocarcinoma, adenocarcinoma and adenocarcinoma in pleomorphic adenoma were placed together (n = 33), and the presence or absence of c-erbB-2 oncoprotein in this group was examined for correlation with patients' survival and other clinicopathological features, including clinical stage, tumor size, surgical margins, and lymph node status. The c-erbB-2-positive tumors tended to be more advanced and larger than negative tumors. Similarly, c-erbB-2-positive tumors were difficult to resect completely, were associated with lymph node metastasis more frequently, and showed lower disease-free survival than negative cases (P less than .05). We conclude that immunohistochemical positivity for c-erbB-2 is an indicator of aggressiveness in both adenocarcinoma and adenocarcinoma in pleomorphic adenoma of the major salivary glands.
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PMID:Immunohistochemical study of c-erbB-2 oncoprotein overexpression in human major salivary gland carcinoma: an indicator of aggressiveness. 135 53

Monoclonal antibody PAb3 to c-erbB-2/neu protein was utilized in the immunoperoxidase staining of 86 human specimens from oral mucosa. These tissue specimens represented a spectrum from 7 normal to 9 simple hyperplasia, 15 mild dysplasia, 14 moderate dysplasia, 20 severe dysplasia and 21 squamous cell carcinoma. Our study indicated that as the cells acquire a more malignant phenotype, there was a progressive increase in neu expression. It also suggested that neu may be involved in the development of oral cancers and that its evaluation in the early stages may assist in the diagnosis and management of oral cancers.
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PMID:Oral cancer progression and c-erbB-2/neu proto-oncogene expression. 135 5

The goal of this study was to evaluate the extracellular matrix (ECM) as a model for growing human lung cancers and to study the feasibility of its application for cellular and molecular studies of tumor biology. Bovine corneal endothelial cell ECM coated dishes were evaluated as a growth substrate for tumor cultures. Growth success, morphology and oncoprotein/growth factor expression for 74 different lung cancers (adenocarcinoma, epidermoid carcinoma and small cell carcinoma) were compared after seeding fresh surgical explants onto bovine corneal endothelial cell ECM and plastic culture substrate. Nineteen out of 74 tumors (26%) plated on ECM demonstrated measurable growth. Growth on ECM was superior to growth on plastic for the lung tumors. All 19 tumor cultures showed malignant morphology and functions. They were examined under the light microscope, and in all cases pre- and post-cytology confirmed malignancy. Tumor cells seeded on ECM retained their malignant phenotype in comparison to tumors grown on plastic. Several oncoproteins (c-myc, c-Ha-ras, c-erbB-2) and growth factors/receptors (EGF, EGF-R, TGF alpha) were immunostained. These analyses were performed immediately after disaggregation of tumor cells obtained surgically and after seeding on ECM or plastic. Strong expression of oncoproteins/growth factors was detected in tumor cells immediately after surgery or when the cells were plated on ECM. On the other hand, moderate or no expression was observed in the same type of cells on plastic.
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PMID:Human lung cancers growing on extracellular matrix: expression of oncogenes and growth factors. 136 16

The c-erbB-2 oncoprotein is a transmembrane protein the presence of which has been associated with poor prognosis in several human neoplasms. However, there has been no comprehensive assessment of its value as a potential prognostic marker in head and neck squamous cell carcinoma. Archival specimens from 93 patients, treated surgically for squamous cell carcinoma of the head and neck between 1981 and 1989, were analyzed by immunohistochemistry using an anti-c-erbB-2 monoclonal antibody; of these, 43 (46%) were positive for c-erbB-2 staining. The majority of stained specimens (41%) displayed staining predominantly at the cell surface, while mixed membrane and cytoplasmic staining was less common (9%). Only 4% shared exclusively cytoplasmic staining. Since the specimens were archival, the cytoplasmic staining is probably a consequence of variable handling and/or fixation at the time of tissue removal. Therefore, only cases exhibiting distinct cell surface membrane staining in more than 10% of tumor cells were regarded as positive. There is a definite association between immunohistochemical detection of c-erbB-2 and head and neck squamous cell carcinoma, since almost half of the tumor specimens manifested detectable c-erbB-2 protein. However, this association could not be extended to a predicted disease progression or outcome, since there was no significant correlation between c-erbB-2 staining and tumor size, stage of disease, histologic differentiation, lymph node status or patient survival.
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PMID:Expression of c-erbB-2 gene in human head and neck carcinoma. 136 18

The epidermal growth factor (EGF) receptor-associated protein tyrosine kinase activity has been suggested to play important roles in the EGF-enhanced, clathrin-coated pit-mediated receptor internalization (W. S. Chen, C. S. Lazar, M. Peonie, R. Y. Tsien, G. N. Gill, and M. G. Rosenfeld, 1987, Nature 328, 820-823) but the kinase substrate important for this process has not been identified. This study demonstrates that the EGF receptor, partially purified from A431 epidermoid carcinoma cells, catalyzes the phosphorylation of one of the two clathrin light chains, clathrin light chain a (LCa). The phosphorylation activity is stimulated by EGF and immunoprecipitated by an EGF receptor monoclonal antibody. The phosphorylation occurs exclusively on tyrosine residues. Amino acid composition of the major tryptic phosphopeptide of the EGF receptor-phosphorylated LCa corresponds closely to that of residues 1 to 97 of LCa. A stoichiometry of 0.2 mol phosphate/mol LCa was attained after 60 min at 30 degrees C and a Km value of 1.7 microM was determined for the reaction. LCa of either neuronal or non-neuronal origin could serve as a substrate. In addition to the EGF receptor tyrosine kinase, a particulate src-related protein tyrosine kinase purified from bovine spleen (C. M. E. Litwin, H.-C. Cheng, and J. H. Wang, 1991, J. Biol. Chem. 226, 2557-2566) was shown in this study to also phosphorylate the light chains. However, in contrast to the EGF receptor phosphorylation, both clathrin light chains a and b were phosphorylated by the spleen kinase, suggesting that the two tyrosine kinases have differential site specificities. Given the specificity of LCa phosphorylation by the EGF receptor, we propose that LCa phosphorylation on a tyrosine residue(s) may be important in EGF-induced receptor internalization.
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PMID:Differential in vitro phosphorylation of clathrin light chains by the epidermal growth factor receptor-associated protein tyrosine kinase and a pp60c-src-related spleen tyrosine kinase. 137 Jun 1

Previous studies have shown that lysine- and arginine-rich proteins can enhance the activity of tyrosine and serine/threonine protein kinases. However, the kinetics and mechanism of this activation are not fully understood. Therefore we investigated the ability of poly(amino acids) and the arginine-rich protein, protamine, to alter the kinetic properties of epidermal growth factor (EGF) receptor protein-tyrosine kinase activity using immunoaffinity-purified receptor isolated from human epidermoid carcinoma (A431) cells. Poly(L-lysine), poly(L-arginine) and protamine stimulated EGF receptor kinase activity by 3-5-fold at non-saturating doses of ATP and peptide substrate, while poly(L-glutamate) had no effect. Initial kinetic studies demonstrated an increase in the maximum velocity and a decrease in the apparent Km for the peptide substrate angiotensin II in the presence of the basic effectors. Further analysis of the kinetic mechanism by product inhibition revealed that protamine altered the pattern of ADP inhibition towards the peptide substrate but not towards ATP. The change was indicative of the receptor's ability to form an enzyme-angiotensin II-ADP ternary complex in the presence of protamine but not in its absence. In addition, the basic effectors had a substantially decreased influence on the kinase activity of a C-terminally truncated form of the EGF receptor. Thus the changes in kinase activity may be partially mediated by the C-terminal region of the receptor, which contains the sites of receptor self-phosphorylation. These results suggest that the basic domains of proteins can interact with the EGF receptor to induce changes in its kinetic properties, especially with regard to reactant recognition and binding.
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PMID:Alteration of the kinetic properties of the epidermal growth factor receptor tyrosine kinase by basic proteins. 137 Jun 7

Forty-seven cases of oral squamous cell carcinoma were examined immunohistochemically by the avidin-biotin peroxidase complex method with anti-epidermal growth factor (EGF) receptor mouse monoclonal antibody, and 24 cases (51%) were shown to have EGF receptor-positive cells. Correlation was strong between presence of EGF receptors and differentiation; the EGF receptor-positive cells were differentiated, whereas poorly differentiated tumors exhibited less intense staining. EGF receptor gene and c-erb B-1 by Southern blot analysis disclosed that one of 25 cases of squamous cell carcinoma exhibited a fourfold amplification of the gene.
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PMID:Evaluation of epidermal growth factor receptor in squamous cell carcinoma of the oral cavity. 160 68

The gene for the epidermal growth factor (EGF) receptor is amplified in a variety of neoplastic tissues, including malignant gliomas. To reveal whether increased sensitivity to EGF has significance for the supply of metabolic substrate to tumor cells, the rate of glucose transport was determined in cells exposed to EGF for up to six hours. In the epidermoid carcinoma line A431, and in primary cultures from 7/12 human glioma biopsies, EGF (10 ng/ml) induced an increase (two-fold) in glucose transport. This effect was transient and independent of protein synthesis.
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PMID:Epidermal growth factor induces glucose transport in primary cell cultures derived from human astrocytic glioma biopsies. 160 38

Many human tumors of epithelial origin contain cells overexpressing the epidermal growth factor (EGF) receptor, and there is convincing evidence that cancer cell growth is correlated with the loss of the normal regulation of the EGF receptor signal transduction pathway. Some cancers are clearly dependent on activation of the EGF receptor for their proliferation. Recently, a class of compounds, tyrphostins, which inhibit the protein tyrosine kinase activity of the growth factor receptor, have been described. In this report, we have examined the antiproliferative effects of potent new tyrphostins on a well-characterized human squamous cell carcinoma in vitro and in vivo. We found that two of these compounds (RG-13022 and RG-14620) suppressed not only EGF-stimulated cancer cell proliferation in vitro but also tumor growth in nude mice. RG-13022 also increased the life span of these tumor-bearing nude mice. When administered to tumor-bearing nude mice together with monoclonal antibodies to the EGF receptor at a suboptimal dose which had no effect alone, inhibition of tumor growth was markedly enhanced. These data suggest that tyrphostins have potential as anticancer agents.
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PMID:The antiproliferative effects of tyrosine kinase inhibitors tyrphostins on a human squamous cell carcinoma in vitro and in nude mice. 165 Nov 59

203 primary human lung tumours, of which 119 were adenocarcinoma and 84 were squamous cell carcinoma, were investigated immunohistochemically for the expression of c-erbB-2 protein. Positive staining was evident in 33 (28%) of adenocarcinomas and 2 (2%) of squamous cell carcinomas. In cases of adenocarcinoma, c-erbB-2 was present in 18% of those with stage I disease. In stage IIIA, stage IIIB and stage IV cases, c-erbB-2 was present in 39%, 50% and 60%, respectively (I vs. IIIA and I vs. IIIB: P less than 0.05, I vs. IV: P less than 0.01). The 5-year survival rates of c-erbB-2 positive patients and those who were negative were 30% and 52%, respectively, with a statistically significant difference (P less than 0.01). These observations suggest that when the expression of c-erbB-2 correlates with invasiveness of the tumour, this correlation may serve as a prognostic indicator, particularly in cases of adenocarcinoma of the lung.
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PMID:Prognostic value of c-erbB-2 protein expression in human lung adenocarcinoma and squamous cell carcinoma. 168 76


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