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

The c-erbB-2 protein in breast cancer tissue extract was determined by using an enzyme-immunoassay (EIA) to see whether the quantitative determination of the oncoprotein correlates with the results of immunohistochemistry and other prognostic factors. Primary breast cancer from 104 patients was assayed for c-erbB-2 protein with an EIA that used two monoclonal antibodies directed against the extracellular domain of the protein. Pelleted tissue homogenate prepared routinely for hormone receptor assay was used as the starting material. The mean quantity of c-erbB-2 protein was 695 unit/mg protein (range 23 to 5939), and this correlated well with the results of immunohistochemical staining (P < 0.00001). It was found that 17.3% (18/104) of all tumors contained amounts of c-erbB-2 protein exceeding 1000 units/mg protein. All tumors with negative or weakly positive staining contained the oncoprotein as less than 1000 units/mg protein. The content of c-erbB-2 protein was correlated with the histologic grade (P = 0.0022), mitotic index (P = 0.0002) and degree of nuclear atypia (P = 0.013). It was inversely correlated with progesterone receptor (P = 0.006) and less strongly with estrogen receptor status (P = 0.016). Values of hormone receptor concentration and c-erbB-2 protein content showed a hyperbolic relationship that suggested biological interactions between c-erbB-2 protein and steroid hormone receptors. We conclude that c-erbB-2 protein in tissue extracts of primary breast cancer can be determined reliably by EIA, and it seems feasible to explore further the advantages of introducing EIA as a routine laboratory examination for providing additional information about the biological aspects of breast cancer.
Jpn J Cancer Res 1993 Dec
PMID:Determination of c-erbB-2 protein in primary breast cancer tissue extract using an enzyme immunoassay. 790 87

One hundred and nine primary breast cancers were analyzed to assess the presence of the HER-2/neu gene product (p185), the oestrogen (ER) and the progesterone (PR) receptors, and the total cathepsin D status. An enzyme-linked immunosorbent assay (ELISA kit, Oncogene Science Inc.) was used for the evaluation of p185 in pellets obtained after a 100,000 x g centrifugation, ER and PR were measured by enzyme immunoassay (EIA kit, Abbott Laboratories), and the total cathepsin D content was evaluated by immunoradiometric assay (IRMA kit, CIS Biointernational). We showed that the ELISA kit is feasible to quantify the p185 present in breast cancer cell membranes, and that the detector antibody recognises a protein of apprroximatly M(r) 185,000. The detected antigen was inversely related to both ER and PR, but it did not correlate to total cathepsin D. No significant differences were found in the expression of p185, ER, PR, cathepsin D between infiltrating ductal carcinomas without special features (NOS) and non-ductal (non-NOS) carcinomas. Nevertheless, in NOS carcinomas, a trend was observed in the p185 levels expressed by the tumours with different histological grades, in that p185 concentration was higher in the poorly differentiated grade 3 with respect to grade 2 and grade 1.
Cancer Lett 1993 Dec 20
PMID:Enzyme-linked immunosorbent assay of HER-2/neu gene product (p185) in breast cancer: its correlation with sex steroid receptors, cathepsin D and histologic grades. 790 96

Transmembrane receptor tyrosine kinases that bind to peptide factors transmit essential growth and differentiation signals. A growing list of orphan receptors, of which some are oncogenic, holds the promise that many unknown ligands may be discovered by tracking the corresponding surface molecules. The neu gene (also called erbB-2 and HER-2) encodes such a receptor tyrosine kinase whose oncogenic potential is released in the developing rodent nervous system through a point mutation. Amplification and overexpression of neu are thought to contribute to malignancy of certain human adenocarcinomas. The search for soluble factors that interact with the Neu receptor led to the discovery of a 44 kDa glycoprotein that induces phenotypic differentiation of cultured mammary tumor cells to growth-arrested and milk-producing cells. The Neu differentiation factor (NDF or heregulin), however, also acts as a mitogen for epithelial, Schwann and glial cells. Multiple forms of the factor are produced by alternative splicing and their expression is confined predominantly to the central and to the peripheral nervous systems. One identified neuronal function of this family of polypeptides is to control the formation of neuromuscular junctions, but their physiological role in secretory epithelia is still unknown. Other open questions relate to the transmembrane topology of various precursors, the identity of a putative coreceptor, the possible existence of additional ligands of Neu and the functional significance of the interaction between Neu and at least three highly related receptor tyrosine kinases.
Bioessays 1993 Dec
PMID:Neu and its ligands: from an oncogene to neural factors. 790 91

The oncogene c-erbB-2 is frequently amplified in human breast carcinoma. The c-erbB-2 gene is present as a single copy in normal cells, and has been mapped to chromosome 17 in the region 17q 12-21.32. c-erbB-2 encodes a transmembrane glycoprotein known as p185. The intracellular component of p185 has tyrosine kinase activity; the extracellular domain has a structure resembling a growth factor receptor. c-erbB-2 amplification, p185 overexpression and levels of transcribed c-erbB-2 specific messenger RNA have been studied in a large number of breast carcinomas using a variety of techniques. In general, overexpression of p185 oncoprotein reflects various levels of DNA amplification, though in some cases amplification can be detected in the absence of overexpression of p185 and similarly overexpression of p185 can be present without detectable levels of c-erbB-2 amplification. This findings suggests that multiple mechanisms may be responsible for overexpression. c-erbB-2 amplification and/or overexpression occurs in almost all cases of high grade duct carcinoma in-situ, but has been reported in only 10%-40% of infiltrating duct carcinoma. c-erbB-2 amplification or overexpression occurs rarely in invasive lobular carcinoma, and has not been detected in ductal or lobular epithelial hyperplasia, or in atypical ductal or atypical lobular hyperplasia. It is generally believed that c-erbB-2 amplification/overexpression is an important independent prognostic indicator in breast carcinoma, identifying a subset of patients with poor prognosis tumours, particularly if axillary node metasases are present. However, many unanswered questions remain regarding c-erbB-2 and its role in breast cancer development and progression. The causes of c-erbB-2 amplification are unknown. There is no evidence of mutations in the human gene which might cause amplification or overexpression. The significance of the differences in levels of c-erbB-2 amplification/overexpression in in-situ duct carcinoma and associated invasive duct carcinoma has not been established. Amplification or overexpression have not been reported in atypical duct hyperplasia, a proposed precursor of duct carcinoma in-situ, yet overexpression occurs almost always in high grade duct carcinoma in-situ. c-erbB-2 may play a critical role in the development of a clonal in-situ, proliferation of high histological grade, yet does not obviously influence the acquisition of an invasive phenotype. We would postulated that this instability in amplification/overexpression is of biological significance, and if better understood may aid in the study of progression of human breast carcinoma.
Pathol Res Pract 1993 Dec
PMID:What's new in breast cancer? Molecular perspectives of cancer development and the role of the oncogene c-erbB-2 in prognosis and disease. 791 Mar 95

Epidermal growth factor receptor (EGFr) levels were analyzed in 140 primary breast cancer specimens by immunohistochemical assay (ICA), competitive binding assay (BA), or enzyme immunoassay (EIA). Thirty-nine of 118 specimens (33.1%) were scored as positive by ICA, 30 of 116 (25.9%; cut-off level 10 fmol/mg protein) by BA, and 31 of 80 (38.9%: cut-off level 5 fmol/mg protein) by EIA. Agreement on EGFr status was 72.3% (68/94) between ICA and BA, 77.0% (57/74) between BA and EIA, and 73.8% (59/80) between EIA and ICA. These discrepancies are based on assay differences and the heterogeneous distribution of cancer cells within specimens. Regardless of the assay method used, EGFr status had a significantly negative correlation with estrogen receptor status. Although EGFr-ICA and BA status had no relationship with prognosis, patients with medium and high EGFr-EIA level tumors (over 5 fmol/mg protein) had shorter relapse-free periods than those with low level tumors. However, the prognostic value of positive EGFr-EIA status was weaker than that of c-erbB-2 overexpression.
Breast Cancer Res Treat 1993 Dec
PMID:Clinical value of enzyme immunoassay of epidermal growth factor receptor in human breast cancer. 791 60

Metastatic phenotype in human solid tumors is believed to follow stochastic acquisition of structural genetic aberrations-so-called multistep tumor progression. We tested this hypothesis in breast carcinoma by immunostaining 89 stage-heterogeneous cases for the products of three genes (p53, ERBB-2, and EGFR) which are frequently altered in this tumor system. Variable relationships were observed between advanced disease stage and immunostaining for individual gene products (ERBB-2 - p = 0.05, EGFR - p = 0.02, p53 - p = 0.12, Chi Square test). Regional or distant metastases at presentation correlated with multiple oncogene/tumor suppressor gene expression abnormalities: node negative -59% none positive, 29% one positive, 12% two or more positive, vs. node positive -37% none positive, 23% one positive, 39% two or more positive (p = 0.01). Only 2/12 (17%) of tumors with distant metastases at presentation were negative for abnormal expression of any of these gene products, and 7/12 (58%) were positive for two or three. Among axillary node negative patients who developed recurrences, 67% exhibited staining for at least one gene product, compared to only 27% of those without recurrences (p = 0.02). All 5 cases with abnormal staining for each gene product had regional or distant metastases at presentation and recurred. In multivariate analysis, individual expression of p53 outweighed expression of ERBB-2 and EGFR in correlation with outcome. These data suggest clinical neoplastic progression of breast carcinomas correlates with cumulative genetic events detectable by protein expression. Short term recurrence, however, may correlate more closely with abnormal expression of p53 than with EGFR or ERBB-2.
Breast Cancer Res Treat 1993 Dec
PMID:Concurrent abnormal expression of ERBB-2, EGFR, and p53 genes and clinical disease progression of breast carcinoma. 791 62

An immunohistochemical study was performed with 130 primary malignant human tumors of breast (n = 55)..colon/rectum (n = 16), stomach (n = 19), esophagus (n = 14), lung (n = 15) and liver (n = 11) using the 21N c-erbB-2 specific monoclonal antibody to identify the tumors that over-expressed the c-erbB-2 oncoprotein. Positivity appeared as an intense brown granular staining located predominantly at the cell membrane. This occurred in 41.8% of breast carcinomas, 12.5% of colorectal adenocarcinomas. None of the gastric adenocarcinomas, squamous cell carcinomas of the esophagus, small cell lung carcinomas or hepatocellular carcinomas were positive for the oncoprotein. The result of this study suggests that over-expression of the c-erbB-2 oncoprotein is common in breast cancer and relatively rare in other malignancies examined.
Asian Pac J Allergy Immunol 1993 Dec
PMID:Expression of c-erbB-2 oncoprotein in primary human tumors: an immunohistochemistry study. 791 4

The protein product of the bcl-2 gene is though to be involved in inhibition of apoptosis; it may therefore be important in the modulation of hormonal/anti-hormonal responsiveness exhibited by tumours. This study immunocytochemically investigates (i) relationships between bcl-2 protein expression in primary breast cancers and other markers of prognostic and therapeutic value and (ii) associations of the bcl-2 protein with breast cancer responsiveness to endocrine therapy. The bcl-2 protein was found within the tumour epithelial cell cytoplasm of 32/46 breast cancer specimens; inter-patient staining was heterogeneous. Immunostaining for steroid hormone receptors was strongly associated with that for the bcl-2 protein, and it is thus possible that this protein, like progesterone receptor, is under oestrogen regulation via oestrogen receptor. The protein was inversely related to 2 markers of endocrine insensitivity, epidermal growth factor receptor (EGFR) and c-erbB-2 oncoprotein, while no associations were observed with either transforming growth factor (TGF)-alpha or Ki-67 proliferative status. A highly significant relationship was observed between response to endocrine therapy and the presence of bcl-2 protein. Indeed, bcl-2 immunostaining proved to be a more accurate predictor of response than oestrogen receptor status. Patients with elevated bcl-2 immunostaining (particularly those who coexpressed high oestrogen receptor levels) appeared to derive the greatest benefit from endocrine therapy. Our results are paradoxical since it was expected that the bcl-2 protein would counteract the tumour inhibitory effects of endocrine therapies as it is thought to prevent programmed cell death.
Int J Cancer 1994 Dec 01
PMID:Immunocytochemical localization of BCL-2 protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy. 796 Feb 34

The c-erbB-2 proto-oncogene encodes a receptor tyrosine kinase (RTK) closely related to the epidermal growth factor receptor (EGFR). Overexpression of erbB-2 occurs in approximately 20% of human breast tumours, where increased expression correlates with poor patient prognosis. The EGFR is coupled to the Ras signalling pathway by interaction with the adaptor protein Grb2, and Sos, a Ras GDP-GTP exchange factor. In this study, activation of the erbB-2 receptor and its association with Grb2 and Sos was investigated in breast cancer cell lines which overexpress erbB-2. The receptor was found to be tyrosine phosphorylated in all cell lines in which it is overexpressed. Western blotting of Grb2 and Sos immuneprecipitates from such cells revealed co-precipitation of erbB-2, demonstrating association of the Grb2/Sos complex with erbB-2 in vivo. Furthermore, a fusion protein containing only the SH2 domain of Grb2 bound to erbB-2 immobilized on nitrocellulose, indicating that association with Grb2 is direct and mediated by the SH2 domain of Grb2. The degree of association between the erbB-2 receptor and Grb2 in vivo was related to erbB-2 overexpression, and MAP kinase, which functions downstream from Ras, displayed markedly increased activity in cell lines overexpressing erbB-2. These results demonstrate that erbB-2 is coupled to Ras signalling via the Grb2/Sos complex, and that overexpression of this receptor in breast cancer cells leads to amplification of the Ras signalling pathway.
Oncogene 1994 Dec
PMID:Activation of the Ras signalling pathway in human breast cancer cells overexpressing erbB-2. 797 Jul 20

The histological hallmarks for the diagnosis of medullary breast cancer are circumscription, syncytial architecture, diffuse inflammatory infiltrate, and highly atypical nuclei. The biological and prognostic implication is a lower propensity to metastasize. We studied 19 medullary carcinomas for expression of the intercellular adhesion molecule-1 and lymphocyte-function-associated antigen-1, Neu differentiation factor, tumor necrosis factor-alpha, and the expression of HER-2/neu, HER-4, and HER-3 receptors. Our study revealed that all of the 19 medullary carcinomas expressed the intercellular adhesion molecule-1 and lymphocyte function associated antigen. Eighteen of 19 cancers expressed Neu differentiation factor and tumor necrosis factor-alpha. All medullary cancers expressed the HER-2/neu receptor, however, in the majority of the cases, the staining was confined to the cytoplasm. Only 4 of 12 cancers expressed HER-4 and none of the eight medullary cancers tested expressed HER-3. By comparison, in a control group of infiltrating ductal carcinomas, expression of intercellular adhesion molecule-1, lymphocyte function associated antigen-1, and Neu differentiation factor was positive in about 25 to 30% of the cases, HER-4 was expressed in 75% and HER-3 in 95% of the cases. Taken together, our observations suggest that the expression of intercellular adhesion molecule-1, lymphocyte function associated antigen, Neu differentiation factor, and tumor necrosis factor-alpha as factors that may affect the special morphology and the biological behavior that characterizes medullary carcinomas.
Am J Pathol 1994 Dec
PMID:Medullary carcinoma is associated with expression of intercellular adhesion molecule-1. Implication to its morphology and its clinical behavior. 799 39


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