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)

Neu differentiation factor (NDF) is a 44-kD glycoprotein which was isolated from ras-transformed rat fibroblasts and indirectly induces tyrosine phosphorylation of the HER-2/neu receptor via binding to either the HER-3 or HER-4 receptor. NDF contains a receptor binding epidermal growth factor (EGF)-like domain and is a member of the EGF family. There are multiple different isoforms of NDF which arise by alternative splicing of a single gene. To date, in vivo biologic activities have not been demonstrated for any NDF isoform. Since NDF, HER-2/neu, and HER-3 are present in skin, and other EGF family members can influence wound keratinocytes in vivo, we investigated whether NDF would stimulate epidermal migration and proliferation in a rabbit ear model of excisional wound repair. In this model, recombinant human NDF-alpha 2 (rhNDF-alpha 2), applied once at the time of wounding, induced a highly significant increase in both epidermal migration and epidermal thickness at doses ranging from 4 to 40 micrograms/cm2. In contrast, rhNDF-alpha 1, rhNDF-beta 1, and rhNDF-beta 2 had no apparent biologic effects in this model. rhNDF-alpha 2 also induced increased neoepidermal expression of alpha 5 and alpha 6 integrins, two of the earliest integrins to appear during epidermal migration. In addition, rhNDF-alpha 2-treated wounds exhibited increased neoepidermal expression of cytokeratin 10 and filaggrin, both epidermal differentiation markers. NDF alpha isoforms were expressed in dermal fibroblasts of wounded and unwounded skin, while both HER-2/neu and HER-3 were expressed in unwounded epidermis and dermal adnexa. In wounds, HER-2/neu expression was markedly decreased in the wound neoepidermis while neoepidermal HER-3 expression was markedly upregulated. Taken together, these results suggest that endogenous NDF-alpha 2 may function as a paracrine mediator directing initial epidermal migration during cutaneous tissue repair.
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PMID:Neu differentiation factor upregulates epidermal migration and integrin expression in excisional wounds. 786 Jul 68

With DNA polymerase chain reaction-single strand conformation polymorphism assay followed by direct DNA sequencing, p53 gene mutation was examined in bladder transitional epithelial cell carcinoma, renal cell carcinoma and testicular seminoma. p53 gene mutation was found in 7 cases (35%) of bladder carcinoma and 4 cases (23.5%) of testicular seminoma. Inactivation of Rb gene and activation of ras and c-erbB-2 were also studied. The results suggest that development of urologic neoplasms is closely associated with p53 gene mutation and involves loss of expression of Rb and aberrant expression of ras and c-erbB-2.
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PMID:[Mechanism of p53 gene mutation in the development of urologic cancer]. 786 97

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

Nineteen paraffin-embedded breast cancer tissue samples selected for long survival (more than 5 years) were analysed for detecting the amplification of the c-erbB-2 (Her-2/neu) oncogene by Polymerase Chain Reaction (PCR). Strong correlation was elucidated between c-erbB-2 amplification and survival; such correlation was also observed with histopathologic types and nuclear grading. Because of the similarity of the breast and ovarian cancer in the etiology of the diseases, amplification of c-erbB-2, c-myc and Ki-ras genes was examined in 32 ovarian carcinoma samples (stage I-IV). In ovarian carcinomas c-erbB-2 amplification occurred in 34% (11/32) of the fresh tumour samples, and correlation between amplification and clinical staging at P < 0.05 significance level was observed. Amplification of c-myc was detected in 9% (3/32) and none of the tumours showed amplification of Ki-ras.
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PMID:Oncogene patterns in breast and ovarian carcinomas. 790 45

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

The protein product of c-erbB-2 and ras oncogene has been examined for its prognostic potential in both node positive and node negative breast cancer. Using a western blot analysis, levels of these proteins were determined in 159 primary human breast tumor specimens. We examined relationships between gene expression and coexpression with other established markers of prognosis, as well as clinical outcome. Multivariate analysis showed that nodal involvement was the most powerful prognostic factor for predicting overall survival (< 0.000) and disease-free survival (p = 0.001), whereas c-erbB-2 expression was second only to nodal status for predicting overall survival in the whole series (p = 0.05). A separated stepwise analysis was conducted for node negative patients who did not receive any kind of adjuvant treatment and for node positive ones who underwent adjuvant chemo or hormonotherapy. c-erbB-2 expression independently predicted poor survival among node negative tumors (p = 0.001) and was associated with ras expression among node positive cases (p = 0.04). If adjuvant treatment is included in the model, coexpressing tumors are less responsive to Tamoxifen and CMF regimens than those with low levels of protein expression (p = 0.04). These results are potentially of clinical value in separating a subset of node positive breast cancer patients for more intense postsurgical treatment. Among node negative patients, the sole expression of c-erbB-2 enhanced levels, is more likely to retain a predictive value in relation to the response after conventional adjuvant treatment.
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PMID:Prognostic and predictive relevance of c-erbB-2 and ras expression in node positive and negative breast cancer. 791 96

Experimental data and clinical observations indicate that an increased expression of oncogenes or their point mutations play an essential role in the process of carcinogenesis. It was important to find out that environmental and occupational carcinogens activate cellular oncogenes and contribute to increased amounts or occurrence of mutated oncoproteins. The latter are responsible for activating mechanisms which further the neoplastic transformation of cells. The researches are mainly concerned about two oncoproteins: oncoprotein coded by the ras oncogene--called p21 protein and oncoprotein coded by the erbB-2 oncogene--called p185 protein. Investigations performed on neoplastic cells show that the neoplastic transformation process involves not only the afore-said oncogenes and their oncoproteins but also other oncogenes, and that the process itself required activating of more than one oncogene. At present, it is possible to use measurements of oncoproteins in the biological material which is easily available. Due to this fact, a number of works in which measurements of oncoproteins in blood serum were used to assess cancer risk in persons exposed to carcinogens present at the work place, have been published.
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PMID:Oncoproteins as biomarkers of a preclinical form of cancer of the respiratory tract induced by environmental carcinogens. 801 97

The importance of epidermal growth factor (EGF) receptor expression level and autophosphorylation sites in src homology and collagen protein (SHC) tyrosine phosphorylation has been studied. In contrast to EGF-induced tyrosine phosphorylation of the GTPase-activating protein for ras (rasGAP) and phospholipase C-gamma 1 (PLC-gamma 1), SHC tyrosine phosphorylation occurs at a very low receptor density in parental NIH3T3 mouse fibroblasts expressing less than 1 x 10(4) EGF receptors per cell. In transfected NIH3T3 cells expressing human EGF receptors (approximately 4 x 10(5) receptors per cell), maximal levels of SHC and PLC-gamma 1 tyrosine phosphorylation occur when approximately 4 x 10(4) receptors or more are occupied by ligand. At lower levels of receptor occupancy only SHC phosphorylation was significant. Also, EGF treatment of mouse keratinocytes, which represent a physiological target of EGF, express a low number of EGF receptors (approximately 2 x 10(4) receptors per cell), and stringently require EGF to grow, results in intense SHC tyrosine phosphorylation, compared to rasGAP or PLC-gamma 1. SHC is also efficiently tyrosine phosphorylated by an EGF receptor deletion mutant (Dc214) that is devoid of autophosphorylation sites, but which remains mitogenically responsive to EGF. The EGF receptor mutant Dc214 is able to activate the ras guanine nucleotide exchanger and phosphorylate mitogen-activated protein kinase (MAPK), presumable as a result of complex formation between tyrosine phosphorylated SHC and GRB2. These results indicate that potent EGF-induced SHC tyrosine phosphorylation can be triggered in cells having relatively few receptors. Also, our data show that EGF receptors are able to phosphorylate SHC, activate the exchange of guanine nucleotide on ras and phosphorylate MAPK by a mechanism that does not require receptor autophosphorylation sites and, therefore, the src homology 2 (SH2):phosphotyrosine-dependent interaction of SHC or GRB2 with the EGF receptor.
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PMID:Potent SHC tyrosine phosphorylation by epidermal growth factor at low receptor density or in the absence of receptor autophosphorylation sites. 803 6

Squamous cell carcinomas of the head and neck from 50 untreated patients were analyzed for rearranged or amplified proto-oncogenes by Southern blot hybridization. The bcl-1 and hst genes were coamplified 8- to 32-fold in 5 of 46 patients (11%) and the c-erb A1 and c-erb B2 genes 32-fold in 1 of 46 patients (2%). Eight to 16-fold amplification of c-myc was observed in 4 of 46 tumor samples (8%), while 4-fold amplification of Ha-ras was found in 2 of 46 tumor samples (4%). There was one patient with a 64-fold c-erb B2 amplification without accompanying c-erb A1 amplification. RNA-expression analysis using Northern blot and poly-A-+RNA techniques did not reveal any changes in the RNA expression of c-erb A1 while c-erb B2, hst and bcl-1 were not expressed at all. No Ki-ras or N-myc amplification was observed, nor was any rearrangement of the above-mentioned oncogenes found. Clinical correlation existed between tumor stage and oncogene amplification: patients with stage I and II disease (IUCC,AJCC) showed no amplification at all, whereas 14 patients with stage III and IV disease showed amplified oncogenes (P = 0.015,chi 2-test). In contrast, there was no correlation between oncogene amplification and disease development (observed over a minimum period of 3 years), nor could amplification be correlated with other clinical parameters (sex, tumor site, -histology) for any of the oncogenes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Detection of 8 oncogenes in squamous epithelial cancers of the head and neck]. 805 Sep 16

A case of extramammary Paget's disease of the axilla in an 84-year-old patient is presented. No underlying carcinoma was found and the lesion was treated successfully by wide local excision. Immunohistochemical staining showed nuclear immunoreactivity for c-myc and cytoplasmic staining for CEA, EMA, CAM 5.2, EGRF, c-erbB-2 and pan-cytokeratin in all the Paget cells. No immunoreactivity of the lesion was observed for S-100 protein, pan-ras, H-ras, K-ras, and p53 oncoproteins. Further research is needed to establish whether oncoprotein overexpression plays a role in the pathogenesis of extramammary Paget's disease and can be used as a diagnostic or prognostic marker.
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PMID:Extramammary Paget's disease of the axilla. 807 May 99


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