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 ontogeny and distribution of the epidermal growth factor (EGF) receptor and lipocortin-1, a major cellular substrate of the EGF receptor, were evaluated in a developmental series of fetal and neonatal human lungs (8 to 41 weeks' gestation and stillborn to 16 days' postnatal age). The peroxidase anti-peroxidase technique with two polyclonal antibodies recognizing the EGF receptor and one polyclonal antibody recognizing lipocortin-1 were used for immunohistochemical localization. Extensive or scattered bronchiolar EGF receptor immunoreactivity appeared in the entire series of frozen lung specimens from 15 to 32 weeks' gestation. Bronchial glands exhibited EGF receptor immunostaining from 19 weeks onward, and immunoreactivity in bronchial epithelium was detected from 23 weeks onward. Most tracheas showed extensive lipocortin-1 immunoreactivity in the epithelium beginning at 10 weeks' gestation. Immunostaining was also seen in cells lining the ducts of submucosal glands after 15 weeks' gestation and in nonmucous acinar cells of tracheal glands after their appearance at 18 weeks' gestation. Bronchial epithelium exhibited lipocortin-1 immunoreactivity from 12 weeks' gestation onward. Bronchial gland necks became immunostained from 16 weeks' gestation onward, followed by acinar immunostaining as they subsequently developed. Bronchiolar epithelium was immunostained as early as 12 weeks, beginning with the largest airways, and by 24 weeks extending distally to the bronchioloalveolar portals. Lipocortin-1 immunostaining of larger conducting airway epithelium was primarily confined to ciliated cells. Neither EGF receptor nor lipocortin-1 immunoreactivity was detected in alveolar type I or type II cells, fibrocytes, chondrocytes, or smooth muscle cells at any gestational age. These developmental patterns suggest that the EGF receptor and lipocortin-1 may participate in normal growth factor-induced proliferation of the conducting airways and their glands in the human fetal lung and trachea.
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PMID:Ontogeny of epidermal growth factor receptor and lipocortin-1 in fetal and neonatal human lungs. 213 10

Various monoclonal antibodies reactive with protooncogene products or tumor-associated antigens have been utilized to investigate breast carcinoma biology or antigen expression with potential prognostic relevance. Murine monoclonal antibody TA1, generated by immunization of BALB/c mice with whole c-erbB-2 (neu) transformed NIH/3T3 cells, recognizes the extracellular domain of the c-erbB-2 protein and binds a Mr 185,000 protein by immunoprecipitation. Using avidin-biotin-peroxidase techniques and monoclonal antibody TA1, 313 archival primary adenocarcinomas of the breast were evaluated for c-erbB-2 overexpression; 290 of these were used for multiparametric statistical analysis. Historical, clinical (age, laterality), histological (nuclear grade, tumor size, lymph node status, lymphatic or blood invasion), and hormone receptor data as well as clinical outcome (minimal follow-up, 6 years; median follow-up, 8.5 years) were compared to TA1 staining. For these 290 patients Cox regression multivariate analysis showed the strongest correlation between lymph node status or estrogen receptor status and overall survival (P = 0.0001 and 0.049, respectively). TA1 staining did not significantly correlate with survival (P = 0.395). However, univariate analysis of certain patient subpopulations showed a significant correlation if the examined tumors were subdivided into negative or focally reactive and those with greater than or equal to 40% cellular reactivity. For T3, T4 patients, strong TA1 immunoreactivity correlated with a shortened disease-free survival (log rank P = 0.0018; Wilcoxon p = 0.0078) and overall survival (log rank P = 0.0002; Wilcoxon P = 0.0013). For these patients the overall survival at 6 years was markedly different between the strongly reactive tumors (0%) and the negative to weakly reactive tumors (55%). In lymph node-positive patients a trend between high TA1 reactivity and a worse overall survival was also noted (log rank P = 0.128; Wilcoxon P = 0.054), with a 6-year survival of 42% in the strongly reactive tumors (n = 16) and 65% in the negative to weakly reactive carcinomas (n = 105). No correlation between TA1 immunoreactivity and other historical, clinical, and histological features were noted. c-erbB-2 overexpression as measured by immunohistochemical techniques, therefore, may have clinical significance in certain patient subpopulations.
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PMID:Analysis of c-erbB-2 expression in breast carcinomas with clinical follow-up. 257 26

We have used a variety of methods, including lactoperoxidase-catalyzed iodination, proteolysis, and photolabel incorporation, to determine whether exposure to the acidic pH encountered during receptor-mediated endocytosis causes observable conformational changes in receptor proteins. Two receptor systems were chosen for this study: the asialoglycoprotein receptor and the epidermal growth factor (EGF) receptor. The purified asialoglycoprotein receptor protein was reconstituted into lipid membranes by spontaneous incorporation into phosphatidylcholine liposomes with the binding site facing outward. The EGF receptor was studied in living A-431 cells and was identified by immunoprecipitation using monoclonal antibodies. Lactoperoxidase-catalyzed iodination of both receptor systems, carried out with the external pH equal to 7.4 or 5.6, showed that the extent of receptor protein iodination was less at the lower pH even though lactoperoxidase has an acidic pH optimum. Using the nonspecific hydrophilic photolabeling agent [35S]N-(4-azido-3-nitrophenyl)-2-aminoethylsulfonic acid-taurine, we observed less incorporation into both the asialoglycoprotein receptor in liposomes and the EGF-receptor in A-431 cells when the external pH was reduced to 5.6. Also, using the enzyme papain, we have found that both receptors become resistant to proteolysis when the external pH is lowered from 7.0 to 5.6. These results suggest a conformational change in both of these receptors in which they become less exposed to the external aqueous environment at low pH. Such a conformational change may be responsible for the pH dependence of binding for both of these ligands. Also, this conformational change may serve to protect receptors from enzymatic degradation within endocytic or lysosomal compartments.
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PMID:Conformational changes in the receptors for epidermal growth factor and asialoglycoproteins induced by the mildly acidic pH found in endocytic vesicles. 608 23

The membranes from epidermoid carcinoma cells (A-431) that were surface iodinated while intact using catalysis by lactoperoxidase and 125I as iodide contain one major labeled protein of Mr = 180,000. This protein is clearly iodinated on the outside of the intact cell because it is not the major protein labeled when isolated membranes are iodinated. This major surface-iodinated protein is almost certainly the epidermal growth factor (EGF) receptor, since both have the same Mr and have identical sensitivity to proteases. Both are nearly quantitatively converted from an Mr = 180,000 form to an Mr = 160,000 form by an endogenous calcium-activated neutral protease when cells are broken in the presence of calcium. Both are degraded by trypsin only if trypsin has access to the inside of the cell. This latter finding implies that the surface-iodinated EGF receptor spans the plasma membrane. Since the EGF receptor is an autophosphorylating kinase whose activity is enhanced in the presence of EGF, the receptor was labeled and identified using [gamma-32P] ATP. While both iodination and EGF-enhanced phosphorylation occur on tyrosine residues, peptide mapping of the iodinated or phosphorylated Mr = 180,000 band showed that different peptides were being labeled. Since the EGF receptor-kinase spans the plasma membrane, the peptide iodinated on the surface of the intact cell must be different from the peptides that are probably autophosphorylated on the cytoplasmic side of the membrane.
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PMID:Surface iodination of epidermal growth factor receptors in intact cells. 632 89

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

A series of 200 breast carcinomas was investigated on frozen sections using PAb 1801 p53 monoclonal antibody and streptavidin biotin peroxidase complex. Densitometric analysis of the immunoprecipitates was assessed by processing digitized microscopic images. p53 was observed in the nucleus of 48% of the tumors. Some tumors (14 of 91) tested in parallel on paraffin sections were negative, although positive on frozen sections. Image analysis showed that the surfaces positive with anti-p53 and the staining intensity were decreased (P < .01) on paraffin sections. The p53 tumor expression was independent of patient age, tumor size, axillary lymph node status, HER-2/neu and cathepsin D expression, and nuclear morphometric parameters. However, p53 correlated with high histological grade (P < .01), lack of estrogen receptor (ER) (P = .0015) and progesterone (PR) (P = .0065) antigenic sites, pS2 detection (P = .03), high Ki-67 immunoreactivity (P = .018), large silver-stained nucleolar organizer region (AgNOR) nuclear surface ratio (P < .02), and degree of hyperploidy (P < .03), and was more often observed in the comedocarcinomas. The results suggest that p53 expression in breast carcinomas is not a totally independent prognostic indicator and that the clinical relevance and prognostic significance of p53 expression in breast carcinomas can be reliably assessed provided that the procedures are standardized, particularly with regard to the use of frozen sections and image analysis processing of the immunodetection.
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PMID:p53 quantitative immunocytochemical analysis in breast carcinomas. 786 46

A Southern blot-based assay is presented that increases the simplicity and accuracy of the HER-2/neu gene copy number assignment in breast cancer DNA. Genomic DNA was hybridized simultaneously with probes corresponding to portions of HER-2/neu and a single-copy gene, myeloperoxidase. A unique restriction fragment was detected for each gene. The use of DNA probes of similar mass and equal specific activities resulted in a ratio of band intensities on the resultant autoradiograph that reported the ratio of gene copy numbers directly. Patient samples containing amplified levels of the HER-2/neu gene were identified by simple visual inspection of a single autoradiograph. Analysis of breast cancer samples alongside the cell line DNAs, representing a range of HER-2/neu gene copy numbers, permits visual quantitation of the tumors' gene copy numbers. The authors show that the HER-2/neu gene copy number can be determined accurately in marginally degraded DNA, a feature of some clinical samples.
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PMID:Improved quantitation of HER-2/neu gene copy number in breast tumor-derived DNA samples. 810 77

The importance of epidermal growth factor receptor (EGF-R) as an immunohistochemical factor of prognosis has been investigated in 820 cases of breast carcinoma irrespective of subtyping. An immunohistochemical membrane positivity for EGF-R (Ab1, clone 455 and Ab2, clone 528, Oncogene Science Manhasset NY, USA, ABC-peroxidase method) has been observed in neoplastic cells of 131/820 breast carcinomas (15.9%); the percentage is lower than those of the majority of reported series, but the total number of cases is higher. A significant inverse relationship between EGF-R and estrogen/progesterone receptors has been found (ER-ICA, PgR-ICA, Abbott, PAP-method). Highly proliferating Ki67 positive (> = 20% stained nuclei-Dakopatts Denmark) and oncoprotein p53 (Pab 1801 clone, Oncogene Science) positive carcinomas are more frequently EGF-R positive (p < 0.001). No relationship exists between EGF-R expression, c-erbB-2 (3B5 clone, Oncogene Science) expression, tumor size and lymph node status. The detection of EGF-R may be a useful addition to other immunohistochemical prognosticators, but it must be related with clinical outcome in further studies.
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PMID:Relationships between epidermal growth factor receptor (EGF-R) and other predictors of prognosis in breast carcinomas. An immunohistochemical study. 817 Jul 12

Manganese superoxide dismutase (Mn-SOD) inactivates the radiation effect by removal of radiation-induced toxic superoxide radicals. The purpose of this study was to assess the correlation among Mn-SOD, radiation sensitivity, and prognosis following radiation therapy. The Mn-SOD, p53 oncoprotein, and c-erbB-2 oncoprotein expressions in 52 specimens from patients with cervical cancer treated with radiation therapy were investigated immunohistochemically. The frozen sections were stained using antihuman Mn-SOD, anti-p53 monoclonal antibodies, and anti-c-erbB-2 oncoprotein polyclonal antibody followed by the avidin-biotin peroxidase complex method. Correlations among Mn-SOD expression, prognosis, and failure patterns were analyzed. Additionally, correlations between p53 and c-erbB-2 oncoproteins and Mn-SOD expression were investigated. Positive expression of Mn-SOD in cervical carcinoma was 48.1%. No significant difference in positivity of Mn-SOD expression was noted according to stage and histological subtypes. The 5-year survival rate of Mn-SOD-positive patients was 42.5 %, significantly poorer than the 77.0% of Mn-SOD-negative patients (P < 0.05). Analysis of the failure patterns revealed that patients with Mn-SOD expression showed a significantly higher incidence of local recurrence than those without. However, there was no difference in distant metastasis between them. Although both p53 and c-erbB-2 oncoprotein expressions were significantly associated with the prognosis of the same patients, Mn-SOD expression was associated with p53 oncoprotein expression but not with that of c-erbB-2 oncoprotein. Our results demonstrate that the Mn-SOD level of cancer cells is correlated with local control and is an important prognostic factor in radiation therapy for cervical cancer. The Mn-SOD level may help explain the intrinsic radiosensitivity of cervical cancer cells.
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PMID:Manganese superoxide dismutase expression correlates with p53 status and local recurrence of cervical carcinoma treated with radiation therapy. 866 12

Twenty-four advanced (surgical stage III and IV) ovarian carcinomas and 15 borderline ovarian tumours were studied for the overexpression of nm23 and HER-2/neu (c-erb-B2) by means of immunohistochemistry on sections from routinely processed, paraffin-embedded, archival tumour blocks, using the NCL-nm23 and the NCL-CB11 monoclonal antibodies and the streptavidin-biotin-peroxidase technique. Significantly more advanced ovarian carcinomas (p = 0.034) expressed high levels of nm23 when compared to borderline tumours. HER-2/neu (c-erb-B2) expression, as could be expected, was also significantly more frequent in advanced ovarian carcinomas (p = 0.006). We were not able to find the previously reported association between nm23 and HER-2/neu overexpression in our tumours. Our results on nm23 overexpression in ovarian cancer are coincident with those previously reported using nm23-mRNA measurements on fresh ovarian tissues. Thus, ovarian carcinoma seems to belong to the group of tumours, like colon carcinoma and neuroblastoma, in which nm23 overexpression is associated with a more malignant phenotype. Immunohistochemistry performed on archival samples from ovarian carcinomas seems adequate for the demonstration of nm23 overexpression in ovarian cancer. This opens the possibility for larger studies on series of patients with a closed follow-up, which could help to establish the role of this gene in this kind of tumour.
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PMID:nm23 expression in advanced and borderline ovarian carcinoma. 870 36


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