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)

We report the localization over the cell surface and the early steps of antibody-induced internalization of the product of the erbB-2 proto-oncogene, structurally related to the epidermal growth factor receptor (EGFR). We show that erbB-2/p 185 is mostly excluded from endocytic pits on the cell surface. Incubation at 37 degrees C with an anti-erbB-2/p185 monoclonal antibody induces the rapid entry of the protein into the cell. Similar internalization is shown by a chimeric molecule EGFR/erbB-2 in response to EGF. Both the timing and the pathway of internalization followed by the erbB-2/p185 appear totally similar to those described for the EGFR. At variance with the normal erbB-2/p185, two mutant activated erbB-2 proteins are frequently localized within endocytic pits of the cell surface, indicating that mutations in the transmembrane regions may determine constitutive internalization of the protein.
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PMID:Surface distribution and internalization of erbB-2 proteins. 135 17

Recently, expectations have been raised that molecular biological studies of human tumours may be of value in helping to predict future clinical behaviour, in terms of therapeutic response and long-term survival. The epidermal growth factor receptor (EGFr) is a cell surface receptor for EGF and transforming growth factor-alpha which is overexpressed by a number of human tumours. This article principally reviews previous investigations of the role of the epidermal growth factor receptor in bladder cancer and examines methods of detection, the correlation between EGFr status and known prognostic indicators and the value of assessing EGFr status in predicting clinical outcome in patients with bladder cancer. Recent studies of the c-erbB-2 proto-oncogene in bladder cancer and of cell cycling using Ki-67 are included.
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PMID:Epidermal growth factor receptor and bladder cancer: a review. 135 9

Post-recurrence survival was examined in 62 breast cancer patients who had undergone curative radical mastectomies between 1974 and 1976 and suffered recurrences within 127 months of surgery. The prognostic value of 11 clinical, histological and genetic factors, including histologic grade of malignancy and amplification of oncogenes was analyzed using univariate and multivariate analyses. Not only the site of first recurrence, clinical stage and size of primary tumor at initial surgery, and disease-free period, but also histologic grade and amplification of the c-erbB-2 proto-oncogene were significant prognostic indicators of recurrent breast cancer. Multivariate analysis using Cox's regression model, histologic grade and amplification of c-erbB-2 in the primary tumor, as well as clinical stage at surgery and site of first recurrence, were shown to be major independent prognostic factors of recurrent breast cancer. Because post-recurrence prognosis was strongly influenced by the clinical, histological and genetic status of the primary breast cancer, appropriate evaluation of the primary tumor for the grade of aggressiveness of the cancer cells, as well as the extent of cancer spread, seem to be important.
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PMID:Prognostic factors for recurrent breast cancer: univariate and multivariate analyses including histologic grade and amplification of the c-erbB-2 proto-oncogene. 135 74

Immunoreactivity of the c-erbB-2 proto-oncogene product and nuclear DNA content were assessed in specimens from 211 breast cancer patients with a mean follow-up of 16 years (range 13-19 years). A routine immunoperoxidase technique was used and cytometrical DNA assessments were performed on cytodiagnostically identified tumour nuclei, using image analysis. C-erbB-2 cell membrane staining was observed in 29% of the cases and was found to be related to tumour size (P = 0.02), histopathological grade (P = 0.02) and nuclear DNA content (P < 0.01). In univariate analysis immunohistochemical c-erbB-2 expression was of prognostic significance among node-positive patients (P = 0.02), but not among women with node-negative disease. This prognostic ability was reduced by multivariate analysis and was no longer significant. In contrast, nuclear DNA content was significantly related to distant recurrence-free survival even in multivariate analysis after adjustment for nodal status and tumour size (P < 0.01). In conclusion, the findings of the present study indicate that c-erbB-2 expression is of limited prognostic value in a subgroup of patients, whereas nuclear DNA content seems to provide significant prognostic information even in node-negative patients.
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PMID:Prognostic significance of immunohistochemical c-erbB-2 proto-oncogene expression and nuclear DNA content in human breast cancer. 136 64

The over-expression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian, endometrial and mammary carcinoma is an important indicator for poor prognosis. We have previously shown in 3 out of 4 ovarian carcinoma cell lines an interferon-gamma (IFN-gamma)-mediated reduction in HER-2 specific protein and RNA levels. The oncogene expression was lowered only in the ovarian carcinoma cell lines but not in 3 IFN-gamma-sensitive human breast cancer cell lines. We extended our observations also to IFN type I, alpha and omega. The expression of the oncogene was measured by both the p185HER-2 ELISA and in selected cases by a living cell radioimmunoassay using the monoclonal antibody (MAb) 4D5 against the extracellular domain. Both IFN types reduced the expression of HER-2 in the ovarian carcinoma cell lines OVCAR-3, HTB-77, 2774 and SKOV-6, and in the SKUT-2 endometrial carcinoma cells. In contrast, SKOV-8 human ovarian carcinoma cells were sensitive for both IFN types regarding proliferation, but only IFN-gamma reduced proto-oncogene expression. In the SKBR-3 human mammary carcinoma cells, neither IFN type had an effect on HER-2 expression. The antibodies 4D5, 7C2, 3E8, and 3H4 which bind to the extracellular domain of p185HER-2 protein specifically inhibited anchorage-independent growth of SKBR-3 and HTB-77 cells. Expression of the oncogene HER-2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which IFNs inhibit cell proliferation.
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PMID:Effects of interferons on the expression of the proto-oncogene HER-2 in human ovarian carcinoma cells. 137 Feb 27

Immunohistochemical c-erbB-2 proto-oncogene expression and nuclear DNA distribution patterns were assessed in 119 formalin-fixed paraffin-embedded surgical specimens of human mammary carcinomas in situ (CIS). The series consisted of 107 ductal carcinomas in situ (DCIS), 9 lobular carcinomas in situ, and 3 cases of Paget's disease of the nipple. Nuclear DNA distribution patterns were assessed by image cytometric analysis of histopathologically identified cell nuclei. Fifty-one of 107 (48%) DCIS were immunoreactive for c-erbB-2, whereas specific cell membrane staining was absent in lobular carcinomas in situ. The neoplastic cell nuclei of 46 CIS (39%) were of DNA diploid type, and 73 CIS (61%) contained aneuploid nuclear DNA. Among various histopathologic subtypes of DCIS, significant differences in c-erbB-2 immunoreactivity and nuclear ploidy were observed. DCIS of the comedo type most often were c-erbB-2 positive and exhibited aneuploid nuclear DNA histograms. DCIS of micropapillary type was the second most frequently reactive c-erbB-2 expression, and aneuploidy were less common in solid, cribriform, and papillary DCIS. The results of the current study indicate that immunohistochemical expression of the c-erbB-2 proto-oncogene product is closely related to the histopathologic subtype and the nuclear DNA content of mammary CIS. Examples of CIS that are c-erbB-2 immunoreactive and DNA aneuploid seem to have a significantly higher risk for the subsequent development of infiltrating mammary carcinoma.
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PMID:Immunohistochemical c-erbB-2 protooncogene expression and nuclear DNA content in human mammary carcinoma in situ. 137 18

The c-erbB-2 proto-oncogene encodes a transmembrane protein which is homologous to the epidermal growth factor receptor. This protein can be localized immunohistochemically in formalin-fixed paraffin-embedded material using a monoclonal antibody NCL-CB11; positive membrane staining correlates with gene amplification and protein overexpression in breast cancer. Using this technique we have shown that only 2/26 (8%) of hepatocellular carcinomas, 0/10 (0%) of cholangiocarcinomas and 0/2 (0%) hepatoblastomas overexpressed c-erbB-2 as evidenced by membrane staining. Moreover c-erbB-2 mRNA was not detected in seven hepatocellular carcinomas examined by Northern blot analysis. c-erbB-2 overexpression is, therefore, unlikely to be contributing to the malignant phenotype in hepatocellular carcinoma and cholangiocarcinoma.
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PMID:c-erbB-2 oncogene expression in hepatocellular carcinoma and cholangiocarcinoma. 138 26

ICR 12, one of a panel of rat monoclonal antibodies recognizing the external domain of the human c-erb B2 proto-oncogene product, (Styles, 1990) was chosen as a candidate for radiolabeling with 124I for positron emission tomography of selected patients with breast cancer. By using N-bromosuccinimide (NBS), optimal labeling conditions were established using 125I. The labeling efficiency was determined using instant thin-layer chromatography (ITLC) and gel filtration (HPLC). The antibody was then labeled with the positron emitter 124I, and a labeling efficiency of 96% and immunoreactivity of 80%-90% was obtained. The product was stable, with less than 5% of the radiolabel being eluted after six days storage in plasma at 37 degrees C. Immunolocalization studies were performed in athymic mice bearing human breast carcinoma xenografts overexpressing the c-erb B2 gene product using as controls 125I labeled isotype-matched rat antibody, and antigen-negative tumors. Good uptake of 124I-labeled ICR12 was obtained in c-erb B2 expressing tumors (up to 12% injected dose per gram at intervals up to 120 hr), with localization indices of 3.4-6.2. Tumor xenografts of 6 mm diameter were successfully imaged with high resolution at 24, 48 and 120 hr using the RMH/ICR MUP-PET camera. We suggest that 124I-labeled ICR12 is a suitable agent to image and quantify immunolocalization in patients whose tumors overexpress the c-erb B2 proto-oncogene product.
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PMID:c-erbB2 protein overexpression in breast cancer as a target for PET using iodine-124-labeled monoclonal antibodies. 146 May 9

The c-myc proto-oncogene was analyzed in 311 cases of primary breast cancer, in 8% of which it was found to be amplified, usually at moderately increased copy number (2-5 copies). The adjacent pvt gene was co-amplified with c-myc in all tumors analyzed. C-myc amplification was significantly correlated to a high S-phase fraction and to amplification of the c-erbB-2 proto-oncogene. Weak relationships were found between c-myc amplification and the presence of lymph-node metastasis, advanced stage, DNA non-diploidy and premenopausal status, but not tumor size, estrogen receptor or progesterone receptor status, or int-2 amplification. C-myc amplification, and especially a high gene copy number (greater than 5 copies), was significantly related to early recurrence and death in breast cancer, a relationship seen in both the lymph-node-negative and node-positive subcategories. A particularly strong correlation with poor clinical outcome was seen in postmenopausal patients (p greater than 0.0005), an association which persisted in multivariate survival analysis. We conclude that the activation of c-myc is indeed associated with rapidly growing and progressive breast cancer. Gene amplification, on the other hand, is relatively infrequent and occurs mostly at low copy number, implying that tumors are heterogeneous with respect to cell clones harboring c-myc amplification. An immunohistochemical assessment would more accurately illustrate the importance of c-myc activation in human breast cancer. However, the obvious instability of the c-myc transcript and translate suggests that c-myc is not a suitable prognostic marker for routine purposes.
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PMID:c-myc amplification is an independent prognostic factor in postmenopausal breast cancer. 161 75

Sections of formalin-fixed, paraffin-embedded primary salivary gland tumours were stained with a monoclonal antibody to the c-erbB-2 oncoprotein to determine the incidence and significance of expression of this protein. The series of 131 tumours comprised 33 cases of pleomorphic adenoma, 2 of malignant mixed tumour, 1 oxyphil adenoma, 31 Warthin's tumours, 4 basal cell adenomas, 6 mucoepidermoid carcinomas, 14 acinic cell carcinomas, 19 adenoid cystic carcinomas, 3 squamous carcinomas, and 18 poorly differentiated adenocarcinomas. Positive staining, as defined in previous studies, was present in five tumours (three cases of poorly differentiated adenocarcinoma, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma). A review of the medical records of all patients did not disclose any clear difference between the clinical behaviour of positive and negative cases over a period of follow-up that ranged from 18 to 120 months. The findings of this study indicate that the protein product of the c-erbB-2 proto-oncogene is infrequently expressed in salivary gland tumours, and when it is localized on the tumour cell surface membrane, there is no clear evidence that this determines the biological behaviour of the tumour.
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PMID:Expression of c-erbB-2 oncoprotein in salivary gland tumours: an immunohistochemical study. 167 54


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