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)

C-erbB-2 (HER-2/neu) proto-oncogene is mainly expressed in epithelial tissue and activated due to its amplification. Amplification of the C-erbB-2 proto-oncogene is associated with poor prognosis in human ovarian cancer. We examined whether amplification of C-erbB-2 is common in ovarian carcinoma or is associated with poor prognosis. The DNA of ovarian carcinoma was extracted and consequently digested with restriction endonuclease EcoRI, electrophoresed in 0.8% agarose gels and blotted onto nitrocellulose filter with Southern transfering method. It was hybridized with a 32p-labelled C-erbB-2 probe and subsequently underwent autoradiography. It was shown that the C-erbB-2 (HER-2/neu) gene was amplified in 8 of 26 human ovarian carcinomas (30.8%). Clinically the 8 patients with the amplified C-erbB-2 were in their advanced stage (III-IV). Five of the patients died from 2 to 4 months after operation. These findings suggest that amplification of the C-erbB-2 gene may play a role in the pathogenesis of ovarian carcinoma, it is frequently observed in advanced ovarian carcinoma and associated with poor prognosis for these patients.
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PMID:[The relation between prognosis and amplification of the c-erB-2 (HER-2/neu) proto-oncogene in ovarian carcinomas]. 786 5

Overexpression of the proto-oncogene product, p185neuN, in a non-tumorigenic mammary epithelial line (31E) facilitates aspects of lactogenic differentiation. Formation of branching cords and induction of beta-casein synthesis by 31E cells normally require co-culture of these cells with fibroblasts, or the presence of collagen or fibronectin. In contrast, 31E cells expressing p185neuN spontaneously form branching cords when grown on tissue culture plastic and can synthesize beta-casein in the absence of exogenous substrates or feeder layers. Under these conditions, the cells deposit laminin and fibronectin, indicating a possible role for p185neuN in the deposition of extracellular matrix proteins. Overexpression of the corresponding oncogene product, p185neuT, has markedly different effects. Expression of p185neuT does not facilitate the formation of branching cords or the synthesis of beta-casein when grown on tissue culture plastic, although these cells do deposit laminin and fibronectin. Confocal microscopy indicates a significant difference in the distribution of laminin and fibronectin in 31E cells expressing p185neuT compared to those expressing p185neuN. The effects of p185neuN and p185neuT expression on cell transformation depend on cell type. Expression of both p185neuN and p185neuT increases anchorage-independent growth of 31E cells, but only p185neuT induces anchorage-independent growth of NIH 3T3 fibroblasts. This lineage specificity in the action of p185neuN may be related to observations that overexpression of p185c-erbB-2 (the human homologue of p185neuN) is only associated with the development of human epithelial cancers. The effects of p185neuN on laminin deposition by 31E cells may be relevant to the transforming ability of p185neuN, since laminin can induce anchorage-independent growth of mouse mammary cells. These results suggest that p185neuN and p185neuT could exert their effects on differentiation and transformation of mammary epithelial cells in part by promoting the deposition of extracellular matrix proteins.
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PMID:The effects of the neuN and neuT genes on differentiation and transformation of mammary epithelial cells. 787 57

Increase of gene activity of the proto-oncogene erbB2 which codes for the transmembrane kinase receptor p185erbB2 has been observed in > 30% of female breast and gynecological carcinomas. This overexpression was shown to be correlated with poor prognosis. We have investigated 38 samples of carcinomas of the male breast for p185erbB2 expression by using tumor thin sections and a monoclonal antibody. The immunostaining was compared to clinical data to assess a possible prognostic value of this parameter. Although most cases were immunopositive (36/38), no correlation to tumor grading and survival spans was notable. Therefore, erbB2 activity fails to add a new prognostic parameter in male breast carcinomas.
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PMID:Expression of the c-erbB2 proto-oncogene in male breast carcinoma: lack of prognostic significance. 790 23

The HER4/ERBB4 gene encodes a 180K transmembrane protein (HER4/p180erbB4) that is structurally related to the 185K product (HER2/p185erbB2) of the HER2/ERBB2 proto-oncogene. A 45K heparin-binding glycoprotein (p45) has been characterized that specifically activates the intrinsic tyrosine kinase activity of HER4 (ref. 2). This HER4 ligand shares several features with the heregulin family of proteins, including molecular mass, ability to induce differentiation of breast cancer cells, activation of tyrosine phosphorylation in MDA-MB453 cells, and amino-terminal protein sequence. Heregulin exists as multiple isoforms and all are presumed to interact directly with HER2 (refs 3-6). We have used binding and phosphorylation studies with recombinant ligand on cell lines expressing recombinant receptors, and report here that heregulin, like p45, is a specific ligand for HER4. Furthermore, heregulin fails to induce phosphorylation of HER2 in the absence of HER4. These findings suggest that activation of the HER4 receptor is involved in signal transduction by heregulin.
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PMID:Heregulin induces tyrosine phosphorylation of HER4/p180erbB4. 790 37

Recently, many alterations in DNA were demonstrated in human breast cancer in vivo, and their clinical and pathological implications were extensively examined. Among these gene alterations, amplification of the c-erbB-2 proto-oncogene and mutation of the p53 tumor-suppressor gene, which occur relatively frequently and are accompanied by alterations in the respective protein levels, demonstrated strong correlation to the histologic grade of atypia and were shown or suggested to be prognostic factors independent of tumor size or lymph node status. Although further analyses are necessary to clarify their prognostic significance in patients without lymph node metastasis, these are suggested to be useful in predicting patient prognosis more accurately and aiding determination of adjuvant systemic therapy.
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PMID:[Clinicopathological implications of gene alterations in breast cancer]. 790 82

The c-erbB-2 proto-oncogene product is expressed in adenocarcinomas of breast cancer and ovarian cancer, and its significance as a prognostic factor has been increasingly noted. We immunohistochemically studied the expression of c-erbB-2 proto-oncogene product using anti-c-erbB-2 gene product polyclonal antibody (Nichirei), which was produced using a synthetic peptide at the C-terminal portion as the immunogen. The subjects consisted of 52 patients with prostatic cancer who were treated at the Department of Urology, Shiga University of Medical Science, from 1982 to 1990. The expression of c-erbB-2 gene was observed in 40 of the 52 patients (76.9%). The positive rate was highest in patients with poorly differentiated cancer and in stage D2 patients, but there were no significant differences in positive rates among patients with different histological types or clinical stages. The probability that progression would occur was significantly (p < 0.05) lower in the group that tested positive for c-erbB-2 than in the group that tested negative among 33 stage D2 patients after 5 years of treatment. When cause specific survival rates were calculated using the Kaplan-Meier method, the group that tested positive had a significantly (p < 0.001) poorer outcome than the group that tested negative after 3 years and 6 months of treatment. The above results suggest that c-erbB-2 expression in prostatic cancer may be useful in predicting the prognosis of the disease.
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PMID:[Immunohistochemical study of c-erbB-2 proto-oncogene product in prostatic cancer]. 790 85

The c-erbB-2 (HER-2/neu) proto-oncogenes is important in oncogenesis and for determination of prognosis in a number of human malignancies. DNA (Southern) hybridization and immunoblotting (Western) techniques are most commonly utilized for determining amplification status and protein expression of this proto-oncogene, respectively. These extraction techniques are often time-consuming, costly, and subject to variability depending on the histological characteristics of the tumor. Paraffin-immunohistochemistry (P-IHC), on the other hand, is time and cost-effective. In addition, this technique may offer enhanced sensitivity and specificity over extraction techniques due to the in situ nature of analysis. In data presented here, 67 cases of human mammary carcinoma were concomitantly assessed for c-erbB-2 gene copy number and oncoprotein expression by dilutional DNA hybridization and P-IHC, respectively. In 64 (95.5%) of 67 cases, high level expression was associated with gene amplification, whereas no detectable expression was associated with a normal diploid gene copy number. In two of the three discrepant cases, P-IHC predicted amplification not corroborated by Southern analysis. In these cases, tumor mass was limited by the intraductal component of the lesion or by an abundance of stromal elements within the specimen. We conclude that P-IHC offers a favorable alternative to Southern analysis in the assessment of c-erbB-2 gene copy number of this oncoprotein in human mammary carcinoma. Furthermore, immunohistochemistry may prove superior to either extraction technique in specimens with limited tumor mass, such as biopsy materials, stroma-rich tumors, or early stage lesions such as intraductal carcinoma.
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PMID:Assessment of c-erbB-2 amplification by immunohistochemistry in paraffin-embedded breast cancer. 790 29

Point mutations of the transmembrane domain coding region of the neu proto-oncogene in N-nitroso-N-ethylurea-induced hamster neurofibromas were found at high frequency (93%; 14 of 15). They involved codons 659 as well as 658, the latter not having been reported previously in rat tumors. The mutational change was seen even in the early stage neurofibroma. On the other hand, no mutations were detected in melanomas or Wilms' tumors induced in the same N-nitroso-N-ethylurea-treated animals, even when the melanomas demonstrated extensive schwannian differentiation. Moreover, any human Schwann cell tumors including neurofibroma, schwannoma, and malignant schwannoma did not show the mutation of c-erbB-2 gene (0 of 34), which is homologous to the hamster neu. Since high expression of neu mRNA is evident in the hamster Schwann cell at the late gestational and neonatal stages, transplacental administration of N-nitroso-N-ethylurea is considered to interact directly to carcinogenesis of the hamster Schwann cell through neu gene mutation.
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PMID:neu proto-oncogene mutation is specific for the neurofibromas in a N-nitroso-N-ethylurea-induced hamster neurofibromatosis model but not for hamster melanomas and human Schwann cell tumors. 790 99

Amplification of the proto-oncogene c-erbB-2 (HER-2/neu) has been shown to be a prognostic marker in ovarian cancer. In order to obtain further information on the biological role of the c-erbB-2 gene product p185 it is necessary to quantify expression levels. In this study we evaluated an enzyme-linked immunosorbent assay (ELISA) for the extracellular domain of p185 to determine whether a soluble oncoprotein fragment can be detected in the serum of ovarian cancer patients and in the serum of pregnant women. Sera from 199 women (57 previously untreated ovarian cancer patients, 62 pregnant women and 80 healthy controls) were assayed in a sandwich ELISA utilizing two mouse monoclonal antibodies. To study c-erbB-2 overexpression in ovarian cancer tissue samples we have used an immunohistochemical technique involving a monoclonal antibody specifically reactive with the external domain of the protein p185. The mean serum value for the normal controls was 1203 HNU/ml with a standard deviation (SD) of 279 HNU/ml and a range of 595-1947 HNU/ml. We chose a level of 1761 HNU/ml (2 SD above the mean) as a cut-off to distinguish individuals with elevated levels. The ovarian cancer patients' serum values ranged from 526 to 16,332 HNU/ml. Immunohistochemically detectable p185 was noted in 8 of 57 ovarian cancer patients. The oncoprotein fragment levels in the sera from these 8 patients ranged from 878 to 16,332 HNU/ml. Of 8 patients with p185 overexpression in their tumors, 4 had elevated serum levels. In the sera from the 49 cancer patients without overexpression the values were distributed in the range 526-2892 HNU/ml. There was no association between serum oncoprotein fragment levels and tumor stage, histological type or grading. Serum concentrations of the p185 fragment in pregnancy ranged from 612 to 3265 HNU/ml. The highest levels were found in the third trimester. The results of the present study raise the possibility that the soluble c-erbB-2 protein level in serum is an indicator for cell proliferation and therefore deserves further evaluation as a diagnostic tool in ovarian cancer patients and pregnancy.
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PMID:Elevated serum levels of a c-erbB-2 oncogene product in ovarian cancer patients and in pregnancy. 790 21

Point mutations of the Syrian hamster neu proto-oncogene have been observed in the transmembrane domain of N-nitroso-N-ethylurea (ENU)-induced neurofibromas. Genomic DNA derived from tumor tissue showed transforming activity in an NIH 3T3 assay and a cDNA clone of the hamster neu gene, containing the entire protein-coding region, was isolated from a transformant cDNA library. The encoded product is 92 and 88% homologous to the rat neu and the human c-erbB-2, respectively. The product of the mutated hamster neu gene showed increased autophosphorylation of Tyr residues.
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PMID:Cloning and activation of the Syrian hamster neu proto-oncogene. 790 75


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