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)

Overexpression of the c-erbB-2 oncoprotein has been detected in human adenocarcinoma of the breast, cervix and salivary gland, in all of which an association between the overexpression of the c-erbB-2 and a poor prognosis of the disease has been reported. However, the prognostic role of c-erbB-2 oncoprotein in ovarian carcinoma remains controversial. We measured c-erbB-2 oncoprotein with an enzyme-linked immunosorbent assay (ELISA). Patients with invasive ovarian cancer were found to have significantly higher median c-erbB-2 oncoprotein expression than patients with either benign ovarian cyst (P = 0.002) or control groups (P = 0.001). Overexpression of c-erbB-2 oncoprotein was found in seven (21.9%) of 32 epithelial ovarian cancers. Our results suggest that quantitative analysis of c-erbB-2 oncoprotein may be used to define the prognostic significance of ovarian carcinoma.
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PMID:c-erbB-2 oncoprotein assay in ovarian carcinoma and its clinical correlation with prognostic factors. 1039 58

Oncogene amplification has been implicated in the genesis and progression of many cancers. Overexpression of the HER-2/neu proto-oncogene occurs in 20-30% of ovarian epithelial cancers, in which it may be of prognostic significance. Oncogene overexpression is traditionally studied using immunohistochemistry. In this study we used fluorescent in situ hybridization (FISH) to determine HER-2/neu amplification in ovarian papillary serous carcinoma and compared the frequency of amplification in two stages of the disease. Archival tissues from 23 cases of papillary serous ovarian carcinoma (9 cases of stage I and 14 cases of stage III) were analyzed by FISH using a HER-2/neu probe and a chromosome 17 centromere control probe. Determination of the level of amplification was performed according to the standard protocols of the Cytogenetics Laboratory at Rhode Island Hospital. Of the 23 cases successfully analyzed, the frequency of amplification among stage I tumors was 22% (2/9) and the frequency of amplification among stage III tumors was 71% (10/14). These results are significant (P = 0.036). The frequency of stage I tumors among amplified cases was 17% (27/12) and the frequency of stage III tumors among amplified cases was 83% (10/12). This study not only confirms the presence of a subset of ovarian papillary serous carcinoma with HER-2/neu gene amplification, but it also indicates that HER-2/neu oncogene amplification is more likely to be associated with a more advanced stage. Thus, the present data are consistent with the hypothesis that HER-2/neu amplification, similar to HER-2/neu protein over expression, is a prognostic marker of poor outcome.
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PMID:HER-2/neu oncogene amplification in stage I and stage III ovarian papillary serous carcinoma. 1040 45

Fcgamma receptor (FcgammaR) engagement is pivotal for many effector functions of macrophages, polymorphonuclear neutrophils (PMN), and natural killer (NK) cells. Mice transgenic for the A and B isoforms of human (h) FcgammaRIII on macrophages, PMN, and NK cells were constructed to permit the study of mechanisms and potential in vivo strategies to utilize the cytotoxic effector and antigen-presenting functions of cells expressing the hFcgammaR. The present report characterizes the phenotypic and functional expression of hFcgammaRIII in transgenic mice derived by crossing hFcgammaRIIIA and hFcgammaRIIIB transgenic mice. Interleukin-2 (IL-2) induces hFcgammaRIII expression by myeloid cells and their precursors, and these transgenic receptors promote in vitro cytotoxicity and anti-hFcgammaRIII antibody internalization. Splenocytes from untreated and IL-2-treated hFcgammaRIIIA, hFcgammaRIIIB, and hFcgammaRIIIA/B mice exhibited enhanced in vitro cytotoxicity toward HER-2/neu-overexpressing SK-OV-3 human ovarian carcinoma cells when incubated with the murine bispecific mAb 2B1, which has specificity for HER-2/neu and hFcgammaRIII. These results indicate that hFcgammaRIII transgenes are expressed on relevant murine cellular subsets, exhibit inducible up-regulation patterns similar to those seen in humans, and code for functional proteins. hFcgammaRIII transgenic mice exhibiting specific cellular subset expression will permit the examination of strategies designed to enhance hFcgammaRIII-dependent immunological effector functions and will provide a model system in which to evaluate preclinically potential candidate molecules that recognize hFcgammaRIII for the immunotherapy of cancer.
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PMID:Production and characterization of mice transgenic for the A and B isoforms of human FcgammaRIII. 1055 May 49

Papillary serous carcinoma of the peritoneum (PSCP) is believed to develop de novo from the peritoneal lining of the pelvis and abdomen. Although it is histologically indistinguishable from serous ovarian carcinoma, PSCP exhibits minimal or absent ovarian involvement and may even develop in a woman years after prophylactic oophorectomy. We have shown previously that patients with germ-line BRCA1 mutations who develop PSCP are more likely to have disease originating from multiple peritoneal sites compared with patients with wild-type BRCA1. In this study, we tested the hypothesis that BRCA1-related PSCP has a unique molecular pathogenesis. DNA was extracted from normal tissue and multiple tumor sites in patients with PSCP. BRCA1 and p53 gene mutations were screened for using single-strand conformation polymorphism. Loss of heterozygosity was determined at the BRCA1 and p53 loci. Immunohistochemical analyses of p53, epidermal growth factor receptor, erbB-2, erbB-3, erbB-4, and Bcl-2 expression were performed. We detected germ-line BRCA1 mutations in 11 (26%) of 43 PSCP patients. BRCA1 mutation carriers had a higher overall incidence of p53 mutations (89% versus 47%; P = 0.052), were more likely to exhibit multifocal or null p53 mutations (63% versus 7%; P = 0.014), and were less likely to exhibit erbB-2 overexpression (P = 0.013) than wild-type BRCA1 case subjects. We propose that the unique molecular pathogenesis of BRCA1-related PSCP may affect the ability of current methods to reliably prevent or detect this disease prior to metastasis.
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PMID:BRCA1-related papillary serous carcinoma of the peritoneum has a unique molecular pathogenesis. 1072 99

Overexpression of HER-2/neu (also known as c-erbB-2) proto-oncogene frequently occurs in many different types of human cancers, including ovarian carcinoma, and is known to enhance tumor metastasis and chemoresistance. Previous studies showed that inhibition of HER-2/neu expression by various agents, such as adenovirus E1A and simian virus 40 large T, can lead to suppression of tumorigenicity of HER-2/neu-overexpressing cancer cells. Here we report that T/t-common, which contains the N-terminal common domain of simian virus 40 large T and small t antigens, could specifically repress the HER-2/neu promoter. When the coding sequence of T/t-common was stably transfected into the HER-2/neu-overexpressing human ovarian carcinoma SK-OV-3 cells, the expression of HER-2/neu was dramatically reduced by the expression of T/t-common. Accordingly the tumorigenic potential of these T/t-common-expressing clones, including the ability to grow anchorage-independently and the ability to induce tumor in nu/nu mice, was also drastically suppressed. Furthermore, when T/t-common was transiently cotransfected with the activated genomic neu into NIH3T3 cells, the transforming activity of the latter was suppressed by T/t-common in soft-agarose microcolony formation assays. Taken together, these data suggest that T/t-common may act as a transformation suppressor of the HER-2/neu oncogene. Oncogene (2000).
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PMID:The N-terminal common domain of simian virus 40 large T and small t antigens acts as a transformation suppressor of the HER-2/neu oncogene. 1085 Oct 70

The HER-2/neu oncoprotein, a 185 kDa membrane-associated tyrosine kinase with extensive homology to the epidermal growth factor receptor (EGF-R), is overexpressed in breast and ovarian carcinomas. Its overexpression is closely associated with poor prognosis in the course of disease. Here we demonstrate HER-2/neu overexpression in both established cell lines and biopsy material obtained from renal epithelial tumors. Immunohistochemical analysis of human kidney tumor lesions using 2 HER-2/neu-specific antibodies revealed HER-2/neu expression in more than 40% of primary epithelial renal tumors and more than 30% of primary renal cell carcinoma (RCC) specimens. A distinctive HER-2/neu expression pattern was found in different subtypes of kidney tumors with the highest frequency in chromophilic and chromophobic RCC, but neither associated with disease stage nor tumor grade. Eight of 10 RCC cell lines expressed significant levels of HER-2/neu mRNA and protein, but at a lower level compared with HER-2/neu overexpressing ovarian carcinoma cells. To evaluate the immune response against HER-2/neu expressing HLA-A2-positive (HLA-A2(+)) RCC cells, allogeneic HLA-A2-restricted cytotoxic T-lymphocyte (CTL) lines generated by pulsing dendritic cells with 3 different HER-2/neu-derived peptides, (HER-2(9.369), HER-2(9.435) and HER-2(9.689), were utilized in chromium-release assays. Specific lysis of HER-2/neu expressing HLA-A2(+) RCC cell lines was mediated by CTL lines specific for each of these 3 HER-2/neu-derived epitopes. The fine specificity of 2 CTL clones was defined to the epitopes HER-2(9.435) and HER-2(9.689). Their specificity was then confirmed by cold target inhibition assays. In addition, CTL-mediated lysis was enhanced by pulsing tumor cells with exogenous HER-2/neu-specific peptides. Our data suggest that (i) HER-2/neu is heterogeneously expressed in different subtypes of RCC, (ii) HER-2/neu is naturally processed by RCC and (iii) HER-2/neu epitopes presented by RCC can be recognized by HLA-A2-restricted, HER-2/neu-specific CTL.
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PMID:HER-2/neu is expressed in human renal cell carcinoma at heterogeneous levels independently of tumor grading and staging and can be recognized by HLA-A2.1-restricted cytotoxic T lymphocytes. 1089 39

Over-expression of epidermal growth factor receptor (EGFR) in ovarian cancer has been well documented. Human NIH:OVCAR-8 ovarian carcinoma cells were transfected with an expression vector containing the anti-sense orientation of truncated human EGFR cDNA. EGFR anti-sense over-expression resulted in decreased EGFR protein and mRNA expression, cell proliferation and tumor formation in nude mice. In accordance with the reduced levels of EGFR in EGFR anti-sense-expressing cells, tyrosine phosphorylation of EGFR was decreased compared to untransfected parental cells treated with EGF. In EGFR anti-sense-transfected cells, expression of erbB-3, but not erbB-2, was increased. In addition, basal and heregulin-beta 1-stimulated tyrosine phosphorylation of erbB-3 was higher in EGFR anti-sense vector-transfected cells. A morphological alteration in EGFR anti-sense gene-expressing cells was correlated with a decrease in the expression of E-cadherin, alpha-catenin and, to a lesser extent, beta-catenin. Changes in the expression of these proteins were associated with a reduction in complex formation among E-cadherin, beta-catenin and alpha-catenin and between beta-catenin and EGFR in EGFR anti-sense-expressing cells compared to sense-transfected control cells. These results demonstrate that EGFR expression in ovarian carcinoma cells regulates expression of cell adhesion proteins that may enhance cell growth and invasiveness.
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PMID:Anti-sense suppression of epidermal growth factor receptor expression alters cellular proliferation, cell-adhesion and tumorigenicity in ovarian cancer cells. 1105 72

Epithelial ovarian cancer is a heterogeneous disease and many biologic and molecular factors are important for its development and progression, including growth rate, metastatic potential, chemo- and radiosensitivity, and prognosis. Even in the early stages (FIGO I-II), many questions persist about the biologic behavior, optimal treatment, and prognosis. In a series of 106 patients with epithelial ovarian cancers in FIGO stages IA-IIC, a number of known prognostic factors (age, FIGO stage, histopathologic type, and tumor grade) were studied in relation to two important growth factor receptors for oncogenesis (HER-2/neu and EGFR). Immunohistochemical techniques were used. All patients received adjuvant radiotherapy 4-6 weeks after the primary surgery. In a univariate analysis, the expression of the HER-2/neu receptor was not associated with any of the clinicopathologic factors studied or survival status. Positive EGFR staining was associated with poor survival in a univariate analysis. Co-expression of HER-2/neu and EGFR was most frequently seen in serous tumors and positive staining for HER-2/neu alone was associated with mucinous tumors. Both endometrioid and clear cell tumors belonged to the largest subgroup with concomitant negativity for both HER-2/neu and EGFR. In a multivariate Cox analysis, the tumor grade and EGFR status of the tumors were independent and significant prognostic factors. A therapeutic strategy for epithelial ovarian cancer might be to decrease EGFR expression by gene therapy in combination with adjuvant radiotherapy or chemotherapy.
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PMID:The growth factor receptors HER-2/neu and EGFR, their relationship, and their effects on the prognosis in early stage (FIGO I-II) epithelial ovarian carcinoma. 1132 10

The prognosis in ovarian carcinoma remains poor. We need to identify patients who are less likely to respond to treatment. In order to evaluate the prognostic value of C-erb-B2, p53 and Ki 67 expression and correlate these markers with classic prognostic factors, we studied paraffin-embedded tumor tissue from 81 patients with epithelial ovarian cancer and made a quantitative evaluation of C-erb-B2, p53 and Ki 67 expression by immunohistochemistry. The results were: age 5.4 +/- 15(22-88); 66% with normal physical activity; 48.2% with residual disease < 2 cm; initial stage--42% and advanced stage--58%. Age, performance status, residual disease and stage were correlated with 2 and 5 years survival. Positive immunostaining: p53--87%, C-erb B-2--51% and Ki67--100%. P53 and C-erb B-2 were associated with residual disease and stage; patients with no C-erbB-2 staining had a significantly better survival. A direct and significant correlation was found between p53 and Ki67 and between C-erb B-2 and p53. We conclude that these markers have a high expression in ovarian carcinoma and p53 and C-er B-2 correlate with stage and residual disease. Although C-erb B-2 was associated with better survival, it was not found to be an independent prognostic factor.
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PMID:[Prognosis value of p53, C-erB-2 and Ki67 proteins in ovarian carcinoma]. 1155 25

The relatively high incidence of amplification and overexpression of the neu (c-erb B2/HER-2) oncogene in breast cancer, and its association with poor prognosis, particularly in node negative patients, may allow identification of patients who require aggressive therapy to prevent an early relapse. It's association with ovarian cancer, however, is less well defined than in breast cancer. An ELISA for the c-neu proto-oncogene related protein, p185, has been developed recently using the monoclonal antibodies NB3 and TA1. In the first study of it's kind, we assayed serum samples from patients with primary epithelial ovarian cancer for circulating c-neu p185. Elevated levels were found in 21/178 (11.8%) patients. No correlation was found between serum levels and either the presence or volume of tumor, when assessed either after primary or at second-look surgery. A change in c-neu p185 levels did not correlate with response to chemotherapy. When subjected to univariate and multivariate analyses together with other known prognostic factors, serum c-neu p185 was not a significant predictor of progression-free survival or overall survival. Although c-neu p185 may be involved in the pathogenesis of ovarian cancer, it's assay in serum has no value in prognosis or monitoring.
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PMID:Investigation of the c-neu proto-oncogene related protein, p185, in the serum of primary epithelial ovarian cancer patients. 1157 48


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