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 HER-2/neu oncogene encodes a Mr 185,000 transmembrane phosphoglycoprotein which is overexpressed in 25-35% of breast and ovarian neoplasms and portends a poor prognosis. We have studied the feasibility of targeting this oncoprotein, designated p185, with radioiodinated murine monoclonal antibodies (muMABs) 4D5 and 7C2, which recognize distinct epitopes on its extracellular domain. The rates of internalization and catabolism of these antibodies were analyzed by cellular radioimmunoassay and electron microscopy. After binding to NIH3T3 HER-2/neu cells, which show high surface expression of p185, the muMABs were endocytosed via coated pits, routed to lysosomes, and degraded. Approximately 44% of 125I-4D5 and 39% of 125I-7C2 were catabolized by tumor cells after 24 h. The biodistribution of radiolabeled 4D5 and 7C2 were evaluated in beige/nude mice bearing s.c. NIH3T3 HER-2/neu grafts. A high specificity of localization was seen with tumor:organ ratios of activity generally ranging from 5:1 to 30:1. However, the percentage injected dose of radioactivity per gram of tumor declined sharply from 25% at 24 h to 5% at 120 h postinjection. Treating the animals with 400-700 muCi 131I-4D5 caused a marked inhibition of tumor growth, although no mice were cured. Unlabeled 4D5 had no effect on tumor progression in this model, but administering 400-700 muCi of 131I-DA4-4, an isotype-matched irrelevant muMAB, resulted in an intermediate degree of growth retardation. Analysis of kinetic blood data and whole-body time-activity curves indicated that the irrelevant conjugate remained in the body 2-3 times longer than 131I-4D5. Radioiodinated anti-HER-2/neu muMABs are attractive agents for radioimmunodiagnosis and radioimmunotherapy of aggressive HER-2/neu-positive breast and ovarian carcinomas, but effective strategies for retarding intratumoral catabolism may be necessary to optimize their clinical utility.
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PMID:Radiolabeled antibody targeting of the HER-2/neu oncoprotein. 134 16

Sections of formalin-fixed, paraffin-blocked tissue from 116 primary transitional cell carcinomas were stained immunohistochemically using a polyclonal antibody against the c-erbB-2 oncoprotein. Positive staining of cell membranes, known to correlate with gene amplification, was seen in 22 (19%) of the 116, with variable staining from tumour to tumour and within tumours themselves. Consistent with its mooted value as a prognosticator in bladder cancer, the c-erbB-2 oncoprotein was detected in 13 (of 40) grade III and 9 of the 26 muscle-invasive tumours examined compared to 1 (of 25) grade I and 6 (of 66) mucosa only (pTa) lesions. These results support further examination of c-erbB-2 expression in bladder cancer.
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PMID:An immunohistological demonstration of c-erbB-2 oncoprotein expression in primary urothelial bladder cancer. 134 55

The neu/HER-2 proto-oncogene (also called erbB-2) encodes a transmembrane glycoprotein related to the epidermal growth factor receptor. We have purified to homogeneity a 44 kd glycoprotein from the medium of ras-transformed cells that stimulates phosphorylation of the Neu protein and retains activity after elution from the polyacrylamide gel. The protein is active at picomolar concentrations and displays a novel N-terminal sequence. Cross-linking experiments with radiolabeled p44 result in specific labeling of Neu, indicating that p44 is a ligand for Neu or a related receptor. The purified protein induces phenotypic differentiation of cultured human breast cancer cells, including altered morphology and synthesis of milk components. This is accompanied by an increase in nuclear area, inhibition of cell growth (probably by cell cycle arrest at the late S or the G2/M phases), and induction of DNA polyploidy. We propose the name Neu differentiation factor (NDF) for p44.
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PMID:Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein that induces differentiation of mammary tumor cells. 134 15

One hundred seventy-nine primary human gastric tumors not associated with early cancer or noncurative resection were examined immunohistochemically for the expression of c-erbB-2 protein. Positive staining, regarded as an indication of gene amplification, was evident in 22(12%) of the tumors. Of various clinicopathological factors considered, a statistically significant difference in association with frequency of expression was noted only for histological differentiation, as follows: 39% positive staining in papillary, 17% in well differentiated, 5% in moderately differentiated, and 4% in undifferentiated adenocarcinomas (P greater than 0.01). The 5-year survival rates of patients with positive and negative c-erbB-2 staining were 57% and 59%, respectively. These findings indicate that, in the case of human gastric adenocarcinoma, expression of c-erbB-2 protein is correlated with tumor histological differentiation. Our results also suggest that the presence or absence of c-erbB-2 protein may not serve as a prognostic indicator, particularly in cases of adenocarcinoma of the stomach.
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PMID:Clinicopathological significance of c-erbB-2 protein expression in human gastric carcinoma. 134 93

This study was aimed at determining whether tumour DNA content measured by cell image analysis could provide additional prognostic information when compared to that provided by flow cytometry. Sections cut from paraffin blocks of tumours from 101 patients with node negative breast cancer were analysed by both methods and the results related to other prognostic variables and to patient relapse and overall survival. DNA ploidy measured by flow cytometry classified 46 tumours as diploid and 55 as aneuploid, whereas by cell image analysis 30 were diploid and 71 aneuploid (P less than 0.002). There were 20 tumours with discrepancies between the two methods; 18 of these were tumours with only one peak in flow analysis, but determined to be aneuploid with image analysis. DNA content as measured by both methods was significant for predicting relapse and survival by log-rank test, as were tumour histological grade, c-erbB-2 expression and tumour size. Multivariate analysis showed DNA ploidy measured by flow cytometry to be the only variable of independent significance (P less than 0.02) for both relapse and overall survival. Compared with cell image analysis, flow cytometry demonstrated a significantly higher proportion of diploid tumours, which may be related to differences in the internal standards applied to each method. We suggest that cell image analysis techniques can provide more sensitive information on the DNA content of tumour cells by direct measurement of nuclear DNA density of both normal lymphocytes and tumour cells in the same section. However, although image analysis appears to be more sensitive than flow cytometry in detecting DNA aneuploidy, the image technique appears to lack the specificity of flow cytometry in correlation with clinical outcome.
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PMID:Predicting outcome for patients with node negative breast cancer: a comparative study of the value of flow cytometry and cell image analysis for determination of DNA ploidy. 134 24

In this investigation, 83 human mammary carcinomas were examined for the expression of oestrogen receptor (ER), epidermal growth factor receptor (EGF-R), epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), c-erbB-2, histological grade, mitotic index and nodal status, all of which are reportedly prognostically significant factors (Bloom and Richardson 1957; Baak et al. 1985; Wright et al. 1989). ER expression was biochemically recognized in 43.4% of mammary carcinomas, and EGF-R, EGF, TGF-alpha and c-erbB-2 were histochemically recognized in 25.3, 14.5, 27.7 and 18.0% of mammary carcinomas examined respectively, using conventional sections of buffered formalin-fixed, paraffin-embedded tissue and monoclonal or polyclonal antibodies. There were significant relationships between negative ER and positive EGF-R or TGF-alpha; positive EGF-R and TGF-alpha; positive EGF-R and c-erbB-2; and positive c-erbB-2 and TGF-alpha. The single changes which were the negative ER and the positive c-erbB-2 correlated with histological grade and mitotic index. Co-expression of EGF-R and TGF-alpha correlated with positive nodal status. Therefore, the present investigation indicates that the negative ER, single expression of c-erbB-2 and co-expression of EGF-R and TGF-alpha are important markers which contribute indirectly to prognosis, which reconfirms previous findings on the former two while adding the new finding that immunohistochemical demonstration of expression of EGF-R and TGF-alpha may provide useful information for selecting the appropriate treatment.
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PMID:Immunohistochemical studies on oncogene products (EGF-R, c-erbB-2) and growth factors (EGF, TGF-alpha) in human breast cancer: their relationship to oestrogen receptor status, histological grade, mitotic index and nodal status. 134 90

The expression of the protooncogene encoded proteins (c-erbB1, c-erb B2, c-myc, c-fos) and the suppressor gene product p53 was analyzed in 81 human squamous cell carcinomas of the lung and correlated with clinical parameters of the patients (patient survival, presence of metastases and tumor stage) and with biological characteristics of the tumors (tumor growth in nude mice, DNA-ploidy, proliferative activity, drug-resistance and P-glycoprotein or gluathione S-transferase expression). By means of immunohistochemistry, expression of c-erbB1 oncoprotein (EGF-receptor) was detected in 79% of the tumors, c-erbB2 (c-neu) proteins in 35%, c-myc proteins in 48%, c-fos proteins in 41%, and p53 in 43% of the tumors. Patients with c-erbB1 positive tumors had a poor prognosis (p = 0.021). In addition, these tumors were more frequently drug resistant (p = 0.0067). A significant correlation between the growth of the squamous lung carcinomas in nude mice and c-fos oncoprotein expression was demonstrated (p = 0.017). Therefore, EGF-receptor and c-fos products may serve as prognostic factors for the aggressiveness of squamous cell carcinomas of the lung and for the response of these tumors to chemotherapy. No significant correlation was found between the expression of the c-erbB1 or c-fos gene products and stage, metastasis and DNA-ploidy. In contrast to these results, no relationship was found between c-neu or c-myc gene products expression and any of the clinical or biological parameters examined. Aneuploid squamous cell carcinomas of the lung expressed p53 more frequently than diploid tumors (p = 0.027). However, there was no significant difference between p53 expression and stage, survival of patients, metastasis, growth of the tumors in nude mice, proliferative activity and drug-resistance of the tumors.
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PMID:Oncoprotein (c-myc, c-erbB1, c-erbB2, c-fos) and suppressor gene product (p53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations. 134 20

Overexpression of normal cellular genes may be one mechanism by which malignant cells can acquire a selective growth advantage. The epidermal growth factor receptor and the c-erbB-2 protein are members of the erbB family and are good examples of genes that appear to act through this mechanism. Molecular and biochemical analyses of these two proteins also illustrate how studies of growth factors, growth factor receptors and oncogenic retroviruses may lead to new approaches to diagnosis and treatment. In particular, overexpression of these growth factor receptors has identified clinical subgroups that may respond differently to chemotherapy and provides the opportunity for antibody targeted therapy. Overexpression of these proteins can be identified using immunocytochemistry on both histological sections and fine-needle aspirates, thus enabling these parameters to be assessed preoperatively and to be monitored during therapy.
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PMID:Identification and interpretation of epidermal growth factor and c-erbB-2 overexpression. 134 53

c-myc, c-erbB-2, and Ki-67 expression was examined by immunohistochemistry in 11 normal breast tissues and 42 invasive and 14 noninvasive breast carcinomas. The c-myc product was detected in all breast carcinoma specimens and in 7 of 11 normal breast tissues. Invasive tumors stained more frequently with the anti-myc monoclonal antibody than did noninvasive tumors, while the level of expression in normal breast tissue was much less than that in breast cancer. Membrane staining of the c-erbB-2 protein was demonstrated in 29% (4 of 14) of noninvasive ductal carcinomas and in 45% (19 of 42) of invasive breast carcinomas. None of the 11 normal breast tissue samples was positive. The mean value of Ki-67-positive cells was 0.91 +/- 0.31% for normal breast tissue, 4.57 +/- 1.36% for noninvasive ductal carcinoma, and 12.76 +/- 2.18% for invasive breast cancer. In 42 invasive breast carcinomas, the expression of c-myc, c-erbB-2, and Ki-67 proliferation marker were compared with lymph node status, estrogen receptor status, progesterone receptor status, and age of patients at diagnosis. c-erbB-2 overexpression and Ki-67 overexpression were identified as the only factors associated with lymph node status. We concluded that they might be additional prognostic factors for breast carcinoma.
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PMID:c-myc, c-erbB-2, and Ki-67 expression in normal breast tissue and in invasive and noninvasive breast carcinoma. 134 67

The erbB oncogene encodes an altered form of the epidermal growth factor (EGF) receptor that lacks the extracellular ligand binding domain. This oncogene is exclusively leukemogenic. However, an increase in oncogenic potential and a broadening of the tissue specificity of tumor formation occurs after retroviral transduction of erbB. The increased oncogenic potential correlates with structural alterations within the erbB gene. One common event is the deletion of a serine phosphorylation site located within the COOH-terminal domain. This site of phosphorylation has been demonstrated to be required for EGF-induced desensitization of signaling by the EGF receptor (Countaway, J. L., Nairn, A. C., and Davis, R.J. (1992) J. Biol. Chem. 267, 1129-1140). Here we show that the mutation of erbB at this negative regulatory serine phosphorylation site causes fibroblast transformation in vitro and is associated with an increased oncogenic potential in vivo.
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PMID:Increased oncogenic potential of ErbB is associated with the loss of a COOH-terminal domain serine phosphorylation site. 134 14


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