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 metastatic variants of human lung adenocarcinoma cell line DMS4C were established by selection in vivo. Lung, brain, spleen and liver metastatic tumors derived from intracarotid inoculation of athymic BALB/c mice were collected, and their corresponding variant cell lines established. The epidermal growth factor (EGF) receptor expression of the parental cell line as well as the metastatic variant cell lines were investigated. 125I-labeled EGF binding assays showed that there were two types of EGF receptors in both parental and metastatic variants. Compared to DMS4C, the EGF binding capacities were found to be down-regulated by 70, 79, 85 and 89% for lung, spleen, liver and brain variant, respectively. The dissociation constants of spleen, liver and brain EGF receptors were distinct from that of the parental cell line. The EGF receptor autophosphorylation activity of lung variant was shown to be down-regulated as shown by immune complex kinase assay that corresponded to EGF receptor numbers whereas kinase activities of the liver, spleen and brain variants EGF receptors were completely abolished. However, the 170 kilodalton EGF receptor was shown to be unaltered during metastasis. The results indicated that, during metastasis progression, the proliferation of adenocarcinoma cells may have adopted a different growth regulation that is independent of EGF receptor kinase-modulated autocrine pathway. The result also implies that other oncogene may emerge as the major growth regulator for distant metastasis of adenocarcinoma cancer cells. This work provides a model for understanding tumor metastasis progression of human lung cancer.
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PMID:Differential down-regulation of epidermal growth factor receptors expressed in the metastatic variants of human lung cancer adenocarcinoma cell line DMS4C. 777 May 48

A three-step immunoperoxidase staining technique was used in order to estimate the immunohistochemical expression of K-ras, c-fos, c-myc and c-erbB-2 oncoproteins, in paraffin sections of 20 patients, with histologically proven adenocarcinoma of the pancreas. The two oncogenes that were found to be associated with pancreatic adenocarcinoma were K-ras and c-erbB-2. in 15 patients (75%) and four patients (20%), respectively. Positive immunostaining was intense, cytoplasmic and was noted in a great percentage of cancer cells. The same model of expression was observed in the examined cases of metastatic tissue from liver and lymph node metastases. The expression of myc and fos oncogenes was nuclear, weak and was observed in a small number of patients.
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PMID:Oncogenes in cancer of the pancreas. 778 91

Intraductal papillary growth of mucin producing hypersecreting, columnar cells characterizes a group of rare pancreatic exocrine neoplasms which we propose to call intraductal papillary-mucinous tumors (IPMT). We analysed the histopathology of 26 IPMT in relation to gastro-enteropancreatic marker expression, genetic changes and biology. Four IPMT showing only mild dysplasia were considered to be adenomas. Nine tumours displayed moderate dysplasia and were regarded as borderline. Severe dysplasia-carcinoma in situ changes were found in 13 IPMT which were therefore classified as intraductal carcinomas. Six of these carcinomas were frankly invasive and two of these had lymph node metastases. The invasive component resembled mucinous non-cystic carcinoma in all but one tumour which showed a ductal invasion pattern. Immunohistochemically, an intestinal marker type was found in most carcinomas, while gastric type differentiation prevailed among adenomas or borderline tumours. K-ras mutations (seven at codon 12 and one at codon 13) were found in 31% of IPMT (2 adenomas, 1 borderline, 5 carcinomas). Nuclear p53 overexpression was detected in 31% of IPMT (6 carcinomas and 2 borderline IPMT) and correlated with p53 mutations (one at exon 8 and the other at exon 5) in two carcinomas. p53 abnormalities were unrelated to K-ras mutation. c-erbB-2 overexpression was observed in 65% of IPMT, with various grades of dysplasia. Twenty-two of 24 patients are alive and well after a mean post-operative follow-up of 41 months. Only two patients, both with invasive cancer at the time of surgery, died of tumour disease. It is concluded that pancreatic IPMT encompass neoplasms which, in general, have a favorable prognosis, but are heterogeneous in regard to grade of dysplasia and marker expression. Adenoma, borderline tumour, intraductal carcinoma and invasive carcinoma can be differentiated. p53 changes but not K-ras mutation or c-erbB-2 overexpression are related to the grade of malignancy. Most IPMT differ in histological structure, marker expression and behaviour from ductal adenocarcinoma.
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PMID:Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients. 782 Mar

p53, p185erbB-2, and epidermal growth factor (EGF) receptor are well-characterized biomarkers in invasive adenocarcinoma of the breast and in ductal carcinoma in situ. erbB-2 Protein (p185erbB-2) must be identified clearly on cytoplasmic membranes while cytoplasmic expression is ignored for breast cancers to be classified as overexpressing p185erbB-2. For p53, nuclear staining and the percent positive cells are considered, but rules for "cut-offs" are not defined. Evaluation criteria for biomarkers in prostate cancer are preliminary and the "rules" may not be the same as for breast cancer. Because the initial methods of fixation and tissue processing can change both the pattern and intensity of immunohistochemical identification of specific antigens and localization of receptors may change after the receptor-ligand interactions, we evaluated the effects of fixation both on the immunolocalization and intensity of expression of p53, p185erbB-2, and EGF receptor. We also studied the patterns of p185erbB-2 and p53 expression in a series of breast cancers evaluated concomitantly with a group of prostate cancers. Our results confirm that p53 mutations are common in breast cancer and that there is strong expression of p185erbB-2 on the membranes of a subset of breast cancers. The patterns of staining for both p53 and p185erbB-2 are different in prostate and breast cancers. A much lower proportion of prostate tumors than breast tumors have more than 10% of tumor cells with detectable nuclear p53 protein, but this proportion increases markedly in metastatic tumors or in primary stage D prostate cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of biomarkers in breast and prostate cancer. 782 98

Adenocarcinomas of the proximal stomach including the gastroesophageal junction are extremely virulent cancers which are increasing rapidly in incidence. Stage-for-stage proximal gastric cancers have a worse prognosis than do tumors of the body or antrum of the stomach. To further explore biological differences based on site, we studied 80 patients with locally advanced primary tumours of the proximal (n = 40) and distal stomach (n = 40) for amplification of the HER-2/neu proto-oncogene. None of 40 patients with proximal lesions had overexpression of HER-2/neu, whereas four of 40 (10%) distal adenocarcinomas had a 16-24-fold gene amplification (P = 0.04). In the adenocarcinomas from two patients, gene rearrangements were found in addition to amplification. HER-2/neu gene product p185 over-expression was found only in the amplified cases. All four patients with distal tumors and amplification had rapid progression of disease (median survival: 4.3 months). While it is unclear why HER-2/neu amplification is seen only in distal tumors, these data further support the hypothesis that biological differences between proximal and distal lesions are present. As is the case for other tumours, HER-2/neu amplification is associated with a poor prognosis for the individual patient.
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PMID:Amplification of HER-2/neu gene in human gastric adenocarcinomas: correlation with primary site. 785 55

To investigate the molecular mechanism of gastric carcinogenesis, we examined simultaneously the frequency of microsatellite instability and the immunoreactivities to ras, erbB-2, and p53 in 42 gastric adenocarcinoma tissues. Microsatellite instability, measured by DNA replication error, was detected in 33.3% (14/42) of patients with gastric carcinoma while positive immunostaining was demonstrated in 3.1% (1/32) for ras, 40.5% (17/42) for erbB-2, and 28.6% (12/42) for p53. There was no statistical difference between the intestinal type and the diffuse type of carcinoma with respect to microsatellite instability, ras, or erbB-2 expression. The expression of p53 occurred more frequently in the intestinal type of carcinoma (41.7%, 10/24) than in the diffuse type of carcinoma (11.1%, 2/18; P < 0.01). There was no association between microsatellite instability and ras or p53 expression, while enhanced expression of erbB-2 occurred more frequently in carcinomas with microsatellite instability (64.3%, 9/14) than in those without microsatellite instability (28.6%, 8/28; P < 0.05). Such a strong association between microsatellite instability and erbB-2 oncogene may be responsible for the increase of other oncogenic mutations and tumor progression in gastric carcinogenesis.
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PMID:Occurrence of microsatellite instability in gastric carcinoma is associated with enhanced expression of erbB-2 oncoprotein. 788 46

Atypical alveolar hyperplasia (AAH) has recently been described in human lungs in association with primary lung cancer, particularly adenocarcinoma. Unlike proximal bronchogenic carcinoma, peripheral (parenchymal) adenocarcinoma of the lung does not have a well-recognized progenitor lesion. Epidemiological morphometric, and cytofluorometric data in the literature suggest that AAH is a candidate premalignant entity. In this study, 97 AAH lesions were found in lungs resected from 29 patients (1-13 lesions per case, mean 3.5) being treated for presumed carcinoma (25/29 had adenocarcinoma). From a study case-load of 285 adenocarcinoma-bearing lungs, the AAH incidence was 8.8 per cent. Sections of 67 AAH lesions from 19 patients were stained using monoclonal antibodies against Ki67 (MIB1), p53 (DO7), and c-erbB-2 (NCL-CB11). Ki67 was expressed in up to 10 per cent of AAH nuclei. Thirty-nine lesions (58 per cent) showed stainable p53 protein, while five (7 per cent) expressed membrane c-erbB-2 oncoprotein. These latter five lesions were all strongly positive for p53, and both p53 and c-erbB staining was associated with increased cellular crowding and pleomorphism in AAH. These data demonstrate that AAH exhibits some genetic changes associated with malignancy and thereby support the hypothesis that AAH is premalignant.
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PMID:Atypical alveolar hyperplasia: relationship with pulmonary adenocarcinoma, p53, and c-erbB-2 expression. 788 86

Adenocarcinoma of the esophagus is an aggressive malignancy which is increasing in frequency. The HER-2/neu oncogene product is a putative differentiation marker which exhibits decreased expression in colon carcinoma, while there is overexpression in breast and ovarian cancers. We analyzed the relationship of cell differentiation to HER-2/neu expression in esophageal adenocarcinoma using immunohistochemistry on formalin-fixed, paraffin-embedded material from 14 patients whose tissue contained normal, dysplastic, and malignant features. HER-2/neu expression was detected in 1 of 14 biopsy specimens and 2 of 9 resection specimens. The oncoprotein staining was greatest in normal tissue, less in dysplastic tissue, and not detected in malignant tissue. Our findings, similar to what is seen in the colon, suggest that the HER-2/neu oncogene product is a differentiation marker which is lost in esophageal adenocarcinoma.
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PMID:HER-2/neu: a differentiation marker in adenocarcinoma of the esophagus. 790 38

We evaluated the prognostic significance of p185c-erbB-2 expression and ras gene mutations in all patients diagnosed with a pulmonary adenocarcinoma between 1982 and 1985 at the University of Iowa. p185c-erbB-2 expression was detected in 15 cases (34%). A ras gene mutation was found in 16 cases (36%) and all were in codon-12 of K-ras. No N-ras mutations were identified. Both p185c-erbB-2 expression and a K-ras mutation were found only in codon-12 and present in six cases (14%). By univariate analysis p185c-erbB-2 expression was associated with shortened survival (P = 0.02) while the presence of a K-ras mutation was not (P = 0.16). Multivariate analysis by the Cox proportional hazards model, controlling for patient age and tumor stage, also continued to identify p185c-erbB-2 expression as an independent unfavorable prognostic factor (P = 0.01). In this model a K-ras mutation also approached significance as a poor prognostic indicator (P = 0.06). The impact of both p185c-erbB-2 expression and a K-ras mutation on survival was additive and highly significant (P = 0.004). This additive nature suggests that together these two markers identify a high-risk population of lung adenocarcinoma patients that may benefit from aggressive therapy.
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PMID:C-erbB-2 expression and codon 12 K-ras mutations both predict shortened survival for patients with pulmonary adenocarcinomas. 790 94

A mouse-human chimeric antibody for erbB-2 product was established by a new procedure using heavy chain loss mouse mutant hybridoma and human immunoglobulin expression vector. The E401 hybridoma secreted anti-erbB-2 product monoclonal antibody (MoAb) (IgG1, kappa). The gene of the mouse variable regions of heavy chain was amplified and cloned by the polymerase chain reaction technique directly from the E401 hybridoma RNA. The variable region of heavy chain was joined with the expression vector, which contains human gamma 1 constant gene. The expression vector was transfected into heavy chain loss mutant cells E401-12, which produced only murine immunoglobulin light chains. A chimeric monoclonal antibody CH401 retained full binding reactivity to erbB-2 product, compared with murine E401 parental antibody. Furthermore, the chimeric MoAb CH401 was much more efficient in supporting antibody dependent cell-mediated cytotoxicity activity against erbB-2-bearing human adenocarcinoma cells than murine MoAb E401. These suggest that a chimeric monoclonal antibody CH401 may be a potent reagent for therapy of human adenocarcinomas.
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PMID:Establishment and characterization of mouse-human chimeric monoclonal antibody to erbB-2 product. 790 85


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