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)

Many human tumors of epithelial origin contain cells overexpressing the epidermal growth factor (EGF) receptor, and there is convincing evidence that cancer cell growth is correlated with the loss of the normal regulation of the EGF receptor signal transduction pathway. Some cancers are clearly dependent on activation of the EGF receptor for their proliferation. Recently, a class of compounds, tyrphostins, which inhibit the protein tyrosine kinase activity of the growth factor receptor, have been described. In this report, we have examined the antiproliferative effects of potent new tyrphostins on a well-characterized human squamous cell carcinoma in vitro and in vivo. We found that two of these compounds (RG-13022 and RG-14620) suppressed not only EGF-stimulated cancer cell proliferation in vitro but also tumor growth in nude mice. RG-13022 also increased the life span of these tumor-bearing nude mice. When administered to tumor-bearing nude mice together with monoclonal antibodies to the EGF receptor at a suboptimal dose which had no effect alone, inhibition of tumor growth was markedly enhanced. These data suggest that tyrphostins have potential as anticancer agents.
Cancer Res 1991 Aug 15
PMID:The antiproliferative effects of tyrosine kinase inhibitors tyrphostins on a human squamous cell carcinoma in vitro and in nude mice. 165 Nov 59

The aim of this study was to investigate papillomavirus (HPV)-DNA in precancer and cancer of the cervix, vulva, and endometrium by in situ/dot blot/Southern blot hybridization and polymerase chain reaction (PCR). Myc/erbB-2 expression was examined by Northern blot analysis. PCR was the most sensitive HPV detection method, demonstrating HPV-DNA in all pre-invasive and invasive cervical lesions (n = 21) and most (3 of 4) vulvar carcinomas in contrast to an overall rate of 60% with other techniques. Particular phenotypes (adenoid cystic/basal cell carcinoma of the vulva, cervical adenocarcinoma) were found to contain HPV. Endometrium harboured HPV not only in two cases of cervical cancer, but also in 3 of 8 primary endometrial carcinomas and 3 of 8 non-malignant conditions. Myc activation was confined to three squamous cell carcinomas, most markedly in one HPV-6-positive verrucous variant. ErbB-2 over-expression was only seen in one HPV-18 infected advanced endometrial tumour. Our findings point to a range of HPV-infected lesions broader than previously supposed and possible contributions of HPV-independent molecular events to carcinogenesis in this field.
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PMID:Human papillomavirus and c-myc/c-erbB2 in uterine and vulvar lesions. 166 Oct 47

Drawing upon the comprehensive population-based Northern Alberta Breast Cancer Registry containing 704 patients with histologically negative axillary lymph nodes who have been followed for 5-16 years, we have undertaken a retrospective case-control study to evaluate the utility of genomic amplification of specific protooncogenes [c-erbB-2 (nee HER-2/neu), c-erbA, c-myc, int-2, and hst-1] as predictive indicators of clinical outcome in node-negative disease. To this end, 115 women with node-negative breast cancer who had recurred at any time up to 16 years posttreatment (cases) were matched pairwise for appropriate clinicopathological variables (size of primary tumor, menopausal state, estrogen receptor status, anniversary year of treatment, and patient age) with a second group of 115 women (controls) selected from a cohort of 502 node-negative patients who had not relapsed during long-term follow-up. Tumor DNA extracted from archival formalin-fixed, paraffin-embedded tissue blocks were analyzed for protooncogene copy number by slot-blot hybridization. Taking a gene copy number of 3 as the cutoff, 27 of the 230 tumor samples examined contained from 3- to 22-fold elevation in c-erbB-2 genomic equivalents. Twenty-one of the 27 tumors amplified for c-erbB-2 were derived from cases and 6 from controls, signifying that 18% of the node-negative patients who had relapsed harbored excessive copies of the protooncogene in their malignant tissue compared to only 5% for the patients who had remained in remission. Accordingly, the occurrence of amplification of c-erbB-2 proved to be a statistically significant predictor of poor prognosis, especially disease-free interval (P = 0.006). Moreover, this genetic alteration appeared to be independent of and to have greater predictive power than most commonly used prognostic factors. Our findings also indicated that as a clinical test, measurement of c-erbB-2 amplification suffers from low sensitivity; however, when greater than 6 gene copies are present, the test has a positive predictive value for recurrence of 70%. Concurrent analysis of tumor DNA blots with probes for the other four protooncogenes examined revealed that their amplification, which others have reported to arise often, especially in node-positive disease, was seldom found even in our high-risk case group (2-3%). In short, our data strongly suggest that amplification of c-erbB-2 may contribute to the pathogenesis of some forms of node-negative breast cancer and thus may serve as a useful genetic marker to identify a subset of high-risk patients.
Cancer Res 1991 Jan 15
PMID:Correlation between c-erbB-2 amplification and risk of recurrent disease in node-negative breast cancer. 167 Jul 62

Prior studies have shown that overexpression of HER-2/neu occurs in one third of breast and ovarian cancers and that overexpression is associated with poor prognosis. We used a monoclonal antibody to assess immunohistochemically the level of HER-2/neu expression in normal and malignant endometrium. In 24 normal endometrial samples light to moderate (1+ to 2+) staining for HER-2/neu was seen in the glands, and there was no variation in intensity of staining during the menstrual cycle. Among 95 endometrial adenocarcinomas, nine (9%) were found to have heavier staining for HER-2/neu than was seen in normal endometrium (3+). High expression of HER-2/neu was found in 27% of patients with metastatic disease compared with 4% of patients with disease confined to the uterus (p less than 0.005). High HER-2/neu expression also was associated with absence of estrogen receptor (p less than 0.005) and with increased mortality from cancer. Further studies are needed to determine the significance of HER-2/neu overexpression in endometrial cancer.
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PMID:Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease. 167 Sep 8

A cytogenetic analysis was performed on direct preparations and short-term cell cultures of lung tumor and normal bronchial epithelium of 19 patients carrying either a first or a second primary lung cancer. In 9 tumors (6 squamous cell carcinomas, 1 adenocarcinoma, 1 mucoepidermoid carcinoma, and 1 small cell lung carcinoma) successfully analyzed, pseudodiploid and hyperdiploid karyotypes were observed with a heterogeneous pattern of chromosome abnormalities but with a consistent involvement (5 cases) of the short or the long arm of chromosome 3. The normal bronchial epithelial cells had a normal karyotype in 11 patients, whereas in 6 patients clonal and nonclonal chromosomal abnormalities were observed. Involvement of chromosome 7 was present in 4 cases. In addition, overexpression of the growth factor receptors, epidermal growth factor receptor and HER-2/neu, was found in 9 of 18 tumors and in 6 of 13 bronchial epithelium samples. These findings suggest that early genetic lesions could be present in the normal bronchial epithelial cells that are the target of further complex and multiple genetic changes occurring during the pathogenesis of lung cancer.
Cancer Res 1991 Jan 01
PMID:Cytogenetic abnormalities and overexpression of receptors for growth factors in normal bronchial epithelium and tumor samples of lung cancer patients. 167 Sep 93

Using a polyclonal antibody that is monospecific for the erbB-2 oncogene product, an immunohistochemical study of the expression of erbB-2 protein was performed in formalin-fixed paraffin-embedded tissue sections from 260 primary gastric cancers. erbB-2 protein expression in which the reaction was localized to the cell membranes was observed in 31 (11.9%) cancers. All nontumor cells and normal gastric epithelium were negative for membrane staining. There was not a significant association between erbB-2 staining and histological type or venous invasion. erbB-2 protein expression was associated with serosal invasion, lymph node metastasis, and lymphatic invasion. In addition, erbB-2 protein expression correlated with a high number of lymph node metastases. Furthermore, the risk of recurrence in lymph node was over 3 times higher in patients with erbB-2 protein-positive tumors than in those with erbB-2 protein-negative ones. When erbB-2 protein expression and the clinical parameters were entered simultaneously into the Cox regression model, erbB-2 protein expression emerged as an independent prognostic indicator. Patients with erbB-2 protein-positive tumors had 5-fold greater relative risk of death, as compared with those with erbB-2 protein-negative tumors. These results indicate that erbB-2 protein expression is an important independent prognostic indicator in gastric cancer. The high malignant potential of erbB-2 protein-positive tumors may be associated with the very high potential for lymph node metastasis.
Cancer Res 1991 Feb 01
PMID:Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. 167 Sep 98

Class-switched monoclonal antibody SV2-61r recognized the extracellular domain of c-erbB-2 protooncogene products separate from the epidermal growth factor receptor. We studied the potential of SV2-61r for evaluating the amplification of c-erbB-2 protooncogene on cancer cells, which has been reported to have prognostic value in adenocarcinoma patients. Radiolabeled SV2-61r specifically bound to various adenocarcinoma cells in addition to c-erbB-2-transfected NIH-3T3 cells (A4) with the affinity constant of 4.4 x 10(8) M-1. SV2-61r injected i.v. localized well to A4 cells xenografted in nude mice. Tumor uptake and localization index of radioiodinated SV2-61r were lower than those of 111In-labeled SV2-61r, probably due to the internalization and dehalogenation of formed antibody-antigen complexes. Biodistribution and specificity of targeting were assessed by comparison among three cells, A4, lung cancer SBC-3 (c-erbB-2 weakly positive) and B-lymphoblastoid Manca cells (c-erbB-2 negative). Tumor:blood ratios, obtained 48 h after injection, were 5.63, 1.45, and 0.68, respectively, indicating the potential of 111In-labeled SV2-61r for evaluating the amplification of c-erbB-2 protooncogene on cancer cells. Because of its close relationship with carcinogenesis and the uniform expression, c-erbB-2 protooncogene products seem to be the optimal target of imaging and therapy of adenocarcinoma patients.
Cancer Res 1991 Feb 01
PMID:Scintigraphic detection of overexpressed c-erbB-2 protooncogene products by a class-switched murine anti-c-erbB-2 protein monoclonal antibody. 167 Oct 1

The expression of the EGF receptor, c-erbB-2 and PDGF receptor proteins has been studied in a series of human brain tumour biopsies and cell lines. Western blotting was used to determine the amount of protein present and their intrinsic and ligand promoted enzyme activities were studied by immunoprecipitation followed by autophosphorylation. EGF receptors were found to be expressed at very high levels in 40% of primary tumour biopsies, but at uniformly low levels in tumour derived cell lines. The c-erbB-2 protein was not detected in tumour biopsies, but was present at variable, but low levels in extracts of tumour cell lines. PDGF receptors were also found at moderate to low levels in both primary tumours and cell lines. The EGF receptor gene was amplified in four out of 14 primary tumours and this generally correlated with high levels of protein expression. The c-erbB-2 gene was not amplified. Employing the polymerase chain reaction and sequence specific oligonucleotides as probes there was no evidence of mutations in the c-erbB-2 gene transmembrane region. These results suggest that alterations of expression of the EGF receptor may play a role in human brain tumours. There was however no evidence for aberrant expression of the c-erbB-2 protein. Additional experiments are required to assess the influence of PDGF receptor expression in brain tumour cells.
Br J Cancer 1991 Feb
PMID:Expression of growth factor receptors in human brain tumours. 167 51

The c-erbB-2 gene is overexpressed in about 20% of human breast cancers. Four hundred and eighty-three cases previously examined by immunohistochemical staining for c-erbB-2 expression were analysed to assess the risk associated with the elevated protein expression. Oncoprotein expression was correlated with increasing tumour grade but not with oestrogen receptor status, nodal involvement, tumour size or age. There was an increased risk of relapse and death associated with c-erbB-2 expression irrespective of nodal involvement. This marker thus appears to be a significant prognostic factor in the early as well as the late stages of breast cancer.
Br J Cancer 1991 Mar
PMID:c-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and uninvolved lymph nodes. 167 53

Immunoreactivity for c-erbB-2 oncogene product expression has been investigated in patients with breast cancer using the polyclonal antibody 21N. Three series of patients were studied, 602 presenting with primary operable cancer, 57 with stage 3 and 123 with stage 4 disease. Representative tissue sections of each primary tumour were stained using a standard immunoperoxidase technique. Invasive tumour membrane immunoreactivity was assessed and identified in 15% of patients with primary operable cancer and 20% in the advanced breast cancer group. The results demonstrate a relationship between poorer survival and oncogene expression in all three patient groups. Patients in the primary operable cancer group with membrane oncoprotein expression had a poorer outcome, 35% 10-year survival, compared with those in which membrane expression was absent, 55% 10-year survival. The median survival of patients with stage 3 disease with c-erbB-2 membrane positivity was 17 months compared to 24 months with membrane negativity. In stage 4 disease median survival with membrane expression was 8.8 months compared to 19.7 months with no membrane expression. In addition in the series of primary cancers a correlation existed between histological grade and membrane immunoreactivity. Multivariate analysis showed histological grade to be a more powerful prognostic factor than c-erbB-2 protein expression. In conclusion, this study demonstrates, in a large series of patients presenting to one centre, that c-erbB-2 protein expression is a prognostic indicator in patients with primary operable and advanced breast disease.
Br J Cancer 1991 Mar
PMID:c-erbB-2 oncoprotein expression in primary and advanced breast cancer. 167 54


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