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 the c-erbB-2 proto-oncogene product was investigated immunohistochemically in 474 formalin-fixed and paraffin-embedded human breast tissue samples. The series included 32 benign and 26 hyperplastic lesions, 32 carcinomas in situ and 384 invasive breast carcinomas, 107 of which were less than 1 cm in diameter. Cytometric DNA assessments were performed on histopathologically or cytodiagnostically identified cell nuclei, using image analysis. C-erbB-2 immunoreactivity was not seen in normal parenchyma or in benign and hyperplastic lesions. Mammary carcinomas in situ were more frequently immunoreactive (59%) than invasive neoplasms (23%). Invasive tumours more than 1 cm in diameter immunoreacted more often (26%) than small invasive carcinomas (16%). C-erbB-2 expression in regional lymph node metastases was the same as in the corresponding primary tumours. Significant differences were observed between the c-erbB-2 expression in DNA diploid and aneuploid lesions; for carcinomas in situ the figures were 40% and 72%, respectively. Invasive carcinomas of DNA diploid type rarely showed c-erb-B-2 expression, irrespective of tumour size and nodal status (7-11%). DNA aneuploid tumours were more frequently immunoreactive with increasing levels during progression (32-41%). Our data indicate that genetically stable invasive mammary tumours seem rarely to express the c-erbB-2 protein, even during progression, whereas genetically unstable invasive neoplasms frequently show c-erbB-2 immunoreactivity which increases during tumour progression.
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PMID:Expression of the c-erbB-2 proto-oncogene product and nuclear DNA content in benign and malignant human breast parenchyma. 135 Jun 95

The prognostic value of c-erbB-2 protein expression was assessed retrospectively in 87 "curative" gastrectomy specimens from patients with gastric carcinoma. Tumours were stained immunohistochemically with the specific antibody 21N. Eight (9%) cases had strong membrane staining, all of which were of the intestinal type, and lymph node metastases, which showed concordance of staining in seven cases. In contrast to studies in breast cancer, positive cases showed a trend towards better five year survival, but this did not reach significance.
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PMID:c-erbB-2 oncogene product expression and prognosis in gastric carcinoma. 135 Jul 89

K1 is a murine monoclonal antibody (MAb) derived from a hybridoma generated by the fusion of splenocytes of BALB/c mice immunized with a human ovarian tumor cell line, OVCAR-3. This antibody reacts strongly with epithelial ovarian tumors and mesotheliomas. The antigen recognized by MAb K1, designated CAK1, has recently been characterized as a 40-kDa protein probably anchored to the cell surface by glycosyl-phosphatidylinositol. Using immunoperoxidase histochemical methods, we examined 37 squamous-cell carcinoma (SqCC) samples from cervix, lung, esophagus and other origins, and 12 normal squamous epithelia of the cervix and esophagus for their reactivity with MAb K1. Of the SqCC specimens, 81% showed K1 reactivity with variable intensity, but none of 12 normal tissue samples of squamous epithelia did so. Two patterns of CAK1 expression in tumor samples were found, i.e., a heterogeneous pattern with strong intensity, and a homogeneous pattern with weak intensity. Three carcinomas in situ of the larynx, vulva and esophagus were moderately positive with K1, suggesting that CAK1 antigen may occur in the early stage of carcinogenesis of SqCC. The expression of CAK1 was also compared with expression of CA125, HER-2/neu, p53 and P-glycoprotein, and MAb K1 was found to react most consistently with SqCC. Since K1 reacts with a majority of cervical and esophageal carcinomas but has no detectable reactivity in normal epithelia of the cervix uteri and esophagus, MAb K1 could be of value as a reagent to help distinguish between normal and neoplastic cells on sections as well as in cytological samples.
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PMID:Frequent expression of the tumor antigen CAK1 in squamous-cell carcinomas. 135 Oct 45

The hormonally induced changes in the breast during pregnancy make the diagnosis of breast cancer difficult. Furthermore, examinations during pregnancy tend to concentrate only on the pregnancy itself. In this report the clinical, pathological and immunohistochemical results from 7 patients with breast cancer during pregnancy are presented. All women first noticed the tumor by self-examination. The time periods between discovery of the tumor and medical treatment were between 4 and 22 weeks. An overexpression of c-erbB-2-oncogene coded transmembrane protein p185 could be demonstrated in 4 cases. Of the seven patients, 5 have already passed away. Three of the deceased had p185-positive tumors, and died 4, 8 and 21 months after diagnosis. The two p185-negative patients lived 34 and 65 months post diagnosis. Despite the small amount of cases presented, a trend can be seen that p185 may be an additional prognostic factor for breast cancer in pregnancy.
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PMID:[Breast carcinoma in pregnancy. Clinical, histological and immunohistochemical findings]. 135 30

In this work, we have used Xenopus oocyte maturation as a read-out for examining the ability of the neu tyrosine kinase (p185neu) to participate with the epidermal growth factor (EGF) receptor in a common signal transduction pathway. We find that unlike the case for the EGF receptor, which elicits EGF-dependent maturation of these oocytes as reflected by their germinal vesicle breakdown (GVBD), neither the normal neu tyrosine kinase (p185val664) nor the oncogenic form of neu (p185glu664) are able to effectively trigger this maturation event. However, expression of p185glu664 causes a specific and significant promotion of the progesterone-induced GVBD, reducing the half-time for this maturation even from approximately 9 h to approximately 5 h. Stimulation of the progesterone-induced GVBD did not occur following the expression of a kinase-deficient p185neu protein (in which a lysine residue at position 758 was changed to alanine). Essentially identical results were obtained when the mRNAs coding for fusion proteins comprised of the extracellular domain of the receptor for immunoglobulin E (IgE), and the membrane-spanning and tyrosine kinase domains of normal or oncogenic p185neu (designated IgER/p185val664 and IgER/p185glu664, respectively), were injected into oocytes. Antigen-induced crosslinking of IgER/p185val164 proteins expressed in oocytes caused a reduction in the half-time for the progesterone-stimulated GVBD from approximately 9 h to approximately 7 h. Thus, the aggregation of the membrane-spanning and/or tyrosine kinase domains of p185val664 partially mimics the effects of the oncogenic forms of p185neu. Overall, the results of these studies suggest that the activation of the p185neu tyrosine kinase by a point mutation within its membrane-spanning helix, or an aggregation event, can result in the facilitation of oocyte maturation events that are elicited by other factors (e.g. progesterone). However, the activated p185neu tyrosine kinases are not able to mimic the EGF-stimulated EGF receptor tyrosine kinase in triggering oocyte maturation, which suggests that the EGF receptor and the p185neu tyrosine kinase do not input into identical signal transduction pathways in these cells.
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PMID:The effects of the normal and oncogenic forms of the neu tyrosine kinase, and the corresponding forms of an immunoglobulin E receptor/neu tyrosine kinase fusion protein, on Xenopus oocyte maturation. 135 69

In previous studies, combinations of immunotoxins reactive with different cell-surface antigens have exerted additive cytotoxicity against tumor cells in culture. In this report we describe a combination of 2 immunotoxins that produce synergistic cytotoxic activity. Recombinantly derived ricin A chain (RTA) was conjugated with murine monoclonal antibodies (MAbs) 317G5, 260F9, 454A12 and 741F8 that bound to cell-surface determinants of 42, 55, 180 (transferrin receptor) and 185 kDa (HER-2/neu) expressed by the SKBr3 human breast-cancer cell line. When inhibition of clonogenic growth was measured in a limiting dilution assay, the combination of 260F9-RTA and 454A12-RTA produced synergistic cytotoxic activity against SKBr3 and 2 other breast-cancer cell lines. All other combinations produced only additive inhibition of clonogenic growth. Simultaneous binding of 260F9 and 454A12 was not supra-additive, but sub-populations of cells which lacked one or the other antigen could be detected. Kinetic studies of internalization, using antibodies conjugated with gold particles, indicated that 454A12 remained within peripheral endosomes for a longer interval in the presence of 260F9. This change in the traffic of the transferrin receptor may contribute to synergy between 260F9-RTA and 454A12-RTA.
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PMID:A combination of two immunotoxins exerts synergistic cytotoxic activity against human breast-cancer cell lines. 135 85

c-erbB-2 protein expression was investigated immunohistochemically in frozen thyroid tissue specimens from 42 patients using a polyclonal sheep antibody. c-erbB-2 immunoreactivity was detected in 12 out of 17 papillary carcinomas, while no c-erbB-2 protein immunostaining was seen in cases of follicular adenoma (five cases), follicular carcinoma (five cases) or medullary carcinoma (one case), nor in cases of non-neoplastic tissue, including normal thyroid tissue from tumour-bearing glands. RNA was extracted from 51 thyroid tissue samples from 34 of the above patients, and c-erbB-2 mRNA was analysed by slot-blot hybridisation. c-erbB-2 mRNA was detectable in all samples, but papillary carcinomas and lymph node metastases showed significantly higher levels of c-erbB-2 mRNA compared to non-neoplastic tissue. The present demonstration of positive c-erbB-2 immunostaining in papillary thyroid carcinomas is contradictory to previous findings on formalin-fixed, paraffin-embedded material, and emphasises the importance of tissue quality for c-erbB-2 protein detection.
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PMID:Expression of c-erbB-2 protein in papillary thyroid carcinomas. 135 25

Autophosphorylation of gp185erbB-2 in vivo is confined to its carboxy terminus and is required for optimal erbB-2 transforming activity under conditions of receptor overexpression. It remains unresolved, however, to what extent autophosphorylation regulates erbB-2 mitogenic signaling in normal cells, nor is the biochemical basis for such a regulatory function known. To address these issues, we utilized a chimeric molecule encompassing the extracellular domain of the epidermal growth factor (EGF) receptor (EGFR) fused to the transmembrane and intracellular domains of the erbB-2 product. In this EGFR/erbB-2 chimera, erbB-2 kinase activity is regulated by EGF binding. An EGFR/erbB-2 mutant bearing multiple Tyr----Phe substitutions at erbB-2 autophosphorylation sites (EGFR/erbB-2 5P) displayed markedly reduced phosphotyrosine content following EGF stimulation in comparison with the non-mutated chimera. When expressed in NR6 cells, the EGFR/erbB-2 5P mutant was unable to deliver a sizeable mitogenic signal when activated by EGF at physiological levels. In intact cells, the 5P mutant was still able to stimulate phosphorylation of the gamma isozyme of phospholipase C (PLC-gamma), a prototype erbB-2 substrate, although with a delayed time course, indicating that the 5P mutation decreased the affinity of the erbB-2 kinase for this substrate. This conclusion was further supported by the inability of the 5P mutant to associate with PLC-gamma in co-immunoprecipitation experiments. We infer that a major role of autophosphorylation is to increase the affinity of the erbB-2 kinase for its cellular substrates, so that, under physiological conditions, autophosphorylation is absolutely required for erbB-2 mitogenic signaling.
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PMID:erbB-2 autophosphorylation is required for mitogenic action and high-affinity substrate coupling. 135 97

Several lines of evidence have demonstrated that expression of the c-erbB-2 gene product contributes to the malignant phenotype. We and others have determined that c-erbB-2 is substantially expressed in most ductal in situ carcinomas of the comedo type, but not in other patterns of ductal carcinoma in situ or in atypical ductal hyperplasia of the breast. In the present investigation, by immunohistochemistry we inquired whether invasive ductal adenocarcinomas retained the c-erbB-2 expression status of the in situ carcinomas from which they derived. Of twelve specimens containing both cribriform/micropapillary in situ and derivative invasive adenocarcinomas in the same section, all tumor cells were negative for c-erbB-2 expression. In thirteen in situ carcinomas of the comedo type, with identifiable invasive components, ten had definite c-erbB-2 expression, and in every case there was comparable c-erbB-2 protein staining of in situ and invasive components; in three of these ten cases the staining in the in situ component tended to be more intense. These findings imply that a significant proportion of invasive mammary adenocarcinomas expressing c-erbB-2 protein is derived from ductal in situ carcinomas of the comedo type.
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PMID:Expression of c-erbB-2 in in situ and in adjacent invasive ductal adenocarcinomas of the female breast. 135 87

The rat neu oncogene product is a member of the epidermal growth factor (EGF) receptor subgroup of the superfamily of growth factor receptor tyrosine kinases. The oncogenic activation of the neu protein occurs by a point mutation within its transmembrane region which results in an increase in its tyrosine kinase activity. Using three different forms of neu expressed in insect cells via baculovirus infection, we have examined the biochemical differences between the normal and transforming forms of neu and investigated the role of the transmembrane domain in its tyrosine kinase activity. One form of neu which was expressed in insect cells consisted of the complete tyrosine kinase domain but lacked the extracellular and transmembrane regions (designated NTK). The other two forms consisted of the tyrosine kinase domain, the transmembrane domain, and 40 amino acids of the extracellular domain. One of these transmembrane forms of neu contained the normal valine residue at position 664 within the transmembrane region (MS-N), while the other contained the oncogenic glutamic acid residue at this position (MS-T). Direct comparisons of NTK, MS-N, and MS-T have shown that the NTK protein is capable of the highest extents of both autophosphorylation activity and the tyrosine phosphorylation of exogenous substrate, suggesting that the presence of the transmembrane region of neu suppresses the tyrosine kinase activity of this receptor. In addition, we have found that the oncogenic point mutation within the transmembrane region stimulates the tyrosine kinase activity of the neu protein by allowing it to more effectively utilize Mg2+. Overall, the results of these studies suggest that the valine to glutamic acid substitution at position 664 may at least partially relieve a negative constraint imparted by the membrane-spanning domain on the tyrosine kinase activity of neu and enables a more effective use of Mg2+ in the catalysis of tyrosine phosphorylation of exogenous substrates.
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PMID:Biochemical comparisons of the normal and oncogenic forms of insect cell-expressed neu tyrosine kinases. 135 72


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