Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alterations in the gene copy numbers of the proto-oncogenes HER2/neu and c-myc in primary human breast cancer investigated in 73 patients. We detected amplification of HER2/neu in 17 patient samples and amplification of c-myc in 11, while amplification of both was seen in 6 samples. There was no correlation of age, hormone receptor positivity or tumour size with amplification of either proto-oncogene. Amplification of HER2/neu was significantly correlated with the stage of the disease. HER2/neu amplification was observed in 18.5% and 38% of node-negative and node-positive patients, respectively; the association between HER2/neu amplification and advanced stage of the disease was statistically significant (p = 0.05). Since this is a prospective study, the clinical significance of oncogene amplification is not known. The relatively high frequency of HER2/neu amplification points to a functional role in human breast cancer, particularly in the progression of the disease. The method used in our study allows oncogene amplification to be studied in conjunction with hormone receptor determination and thus may be of value in large clinical trials to determine the significance of oncogene abnormalities in breast cancer.
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PMID:The significance of oncogene amplification in primary breast cancer. 256 20

The neu oncogene, characterized by Weinberg and colleagues, is a transforming gene found in ethylnitrosourea-induced rat neuro/glioblastomas; its human proto-oncogene homologue has been termed erbB2 or HER2 because of its close homology with the epidermal growth factor receptor (EGF-R) gene (c-erbB1). Expression of the rat neu oncogene is sufficient for transformation of mouse NIH 3T3 fibroblasts in culture and for the development of mammary carcinomas in transgenic mice, but the neu proto-oncogene has not been associated with cell transformation. We constructed a vector for expression of a chimeric cDNA and hybrid protein consisting of the EGF-R extracellular, transmembrane and protein kinase C-substrate domains linked to the intracellular tyrosine kinase and carboxyl terminal domain of the rat neu cDNA. Upon transfection with the construct, NIH 3T3 cells gave rise to EGF-R antigen-positive cell clones with varying amounts of specific EGF binding. Immunofluorescence and immunoprecipitation using neu- and EGF-receptor specific antibodies demonstrated a correctly oriented and positioned chimeric EGF-R-neu protein of the expected apparent mol. wt on the surface of these cells. EGF or TGF alpha induced tyrosine phosphorylation of the chimeric receptor protein, stimulated DNA synthesis of EGF-R-neu expressing cells and led to a transformed cell morphology and growth in soft agar. In contrast, the neu proto-oncogene did not show kinase activity or transforming properties when expressed at similar levels in NIH 3T3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A chimeric EGF-R-neu proto-oncogene allows EGF to regulate neu tyrosine kinase and cell transformation. 256 7

We have investigated the biological function of an unidentified human growth factor, the ligand of the putative HER2 receptor, by characterizing the signalling properties of its receptor. HER2 (or c-erbB-2), the human homolog of the rat neu proto-oncogene, encodes a transmembrane glycoprotein of the tyrosine kinase family that appears to play an important role in human breast carcinoma. Since a potential ligand for HER2 has not yet been identified, it has been difficult to analyze the biochemical properties and biological function of this cell surface protein. For this reason, we replaced the HER2 extracellular domain with the closely related ligand binding domain sequences of the epidermal growth factor (EGF) receptor, and examined the ligand-induced biological signalling potential of this chimeric HER1-2 protein. This HER1-2 receptor is targetted to the cell surface of transfected NIH 3T3 cells, forms high and low affinity binding sites, and generates normal mitogenic and cell transforming signals upon interaction with EGF or TGF alpha. The constitutive activation of wild-type HER2 in transfected NIH 3T3 cells suggests the possibility that these cells synthesize the as yet unidentified HER2 ligand and activate HER2 by an autocrine mechanism.
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PMID:HER2 cytoplasmic domain generates normal mitogenic and transforming signals in a chimeric receptor. 256 8

The mouse monoclonal antibody (mAb) 225 IgG1 against the epidermal growth factor (EGF) receptor has been investigated for its capacity to localize in human tumor xenografts. The EGF receptor is the product of the c-erb-B proto-oncogene (also known as EGFR). Elevated expression of EGF receptors has been demonstrated in many human tumors and tumor cell lines. We studied A431 human vulvar squamous cell carcinoma cells, with 2 X 10(6) receptors per cell; MDA-MB-468 (MDA 468) human breast adenocarcinoma cells, with 3 X 10(5) receptors per cell; and MCF-7 human breast adenocarcinoma cells, with 5 X 10(3) receptors per cell. The 111In-labeled pentetic acid (DTPA), derivative of mAb 225 (111In-DTPA-225) was injected intraperitoneally into nude mice bearing subcutaneous tumor xenografts. We measured uptake by quantifying radioactivity in tumor and normal tissues and by obtaining gamma camera images. Uptake in A431 xenografts was 28% +/- 2.4% of the injected dose per gram of tumor on day 3 and 12.4% +/- 3.0% on day 7. Distribution ratios comparing uptake in the tumor with that in normal tissues were consistently greater than 4. In contrast, there was far less uptake of the control mAb KS1/4S-1 labeled with 111In. This conjugate, 111In-DTPA-KS1/4S-1, has an IgG1 isotype but does not bind to human or murine cells. Imaging of the tumor with mAb 225 was excellent, especially on days 3-7. MDA 468 xenografts exhibited reduced localization of mAb 225 in the tumor. For MCF-7 xenografts, the tumor uptake of mAb 225 after 7 days was only 0.70% +/- 0.10% of the injected dose per gram of tumor, which was comparable to the uptake of the KS1/4S-1 control mAb. The ratio of the concentration of radioactivity in the tumor to that in normal tissue (distribution ratio) showed poor selectivity of uptake, and imaging was not obtained. These observations suggest that labeled mAb can target the product of a proto-oncogene, the EGF receptor, when it is expressed at high levels in human tumor xenografts.
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PMID:Imaging of human tumor xenografts with an indium-111-labeled anti-epidermal growth factor receptor monoclonal antibody. 279 90

Abnormalities of chromosome 7 are among the most frequent cytogenetic aberrations found in MDS, including de novo cases and cases secondary to chemo- and/or radiotherapy. Since MET is located on 7q and as Cooper et al (1984) showed that MET proto-oncogene could be activated by a chemical carcinogen, we tried to evaluate whether it could be implicated in some cases of MDS. With specific probes for MET we analysed the DNA of 88 MDS patients (81 de novo and seven secondary cases). In 17 of them the RNA was also studied. We found no rearrangement or aberrant expression of MET in any samples studied. Our results, however, do not rule out point mutations or rearrangement of other regions of MET or adjacent DNA regions.
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PMID:Absence of rearrangement of proto-oncogene MET in 88 cases of myelodysplastic syndromes (MDS). 280 76

A candidate gene for cystic fibrosis was recently isolated by selective cloning of HpaII-tiny-fragment islands; it maps considerably closer to CF than does MET or D7S8 (pJ3.11), and DNA polymorphisms from this region are in marked disequilibrium with CF. cDNA cloning has shown that this protein has a growth factor-like structure and shows homology to the murine and human proto-oncogene int-1; it is designated IRP (int-1-related protein). DNA sequences from the IRP locus that recognize RFLPs are proving to be highly informative for prenatal diagnosis. We report five crossovers that have been identified which occur either within the IRP locus or between IRP and CF; these recombinants demonstrate that CF maps between the DNA markers D7S8 and KM.19.
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PMID:Recombinations between IRP and cystic fibrosis. 197 Nov 40

Amplification of the neu proto-oncogene in breast cancer has been reported to correlate with the presence of lymph-node metastases and with a poor prognosis. We describe a method for the immunohistochemical detection of overexpression of neu protein on formalin-fixed paraffin-embedded tissue, with the use of two different monoclonal antibodies. In a group of tumors with a known neu-gene copy number, intense membrane staining of tumor cells was present in all tumors with neu-gene amplification. Of 189 tumors from patients with Stage II breast cancer, 27 (14 percent) had neu-membrane staining. Neu overexpression was associated with larger tumor size (P = 0.006) but not with lymph-node involvement. Neu-protein expression in lymph-node metastases was the same as its expression in primary tumors. Among the patients with neu overexpression (median follow-up, 37 months), disease-free survival was not significantly shorter; overall survival was reduced significantly in these patients (P = 0.042), but this reduction did not remain significant after adjustment for tumor size. Of 45 ductal carcinomas in situ, 19 (42 percent) had neu-membrane staining. These 19 were all of the large-cell, comedo growth type. None of 16 ductal carcinomas in situ of small-cell, papillary, or cribriform growth type had neu overexpression. We conclude that neu overexpression may be an early step in the development of a distinct histologic type of carcinoma of the breast, but we could find no association of overexpression with lymph-node status or tumor recurrence.
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PMID:Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. 290 46

Chinese hamster X mouse somatic cell hybrids were analyzed by Southern blot hybridization with a probe specific for the cellular c-fms proto-oncogene. Results demonstrate that Fms, the genetic locus containing this sequence, maps to mouse chromosome 18. Mouse Fms is thus not linked to the same set of genes involved in growth regulation that human FMS is linked to.
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PMID:Genetic mapping of the mouse c-fms proto-oncogene to chromosome 18. 296 40

In order to characterise the distribution and role of stem cell factor (SCF), a recently-reported growth factor for normal melanocytes, we carried out an immunohistochemical study on benign and malignant melanocytic tumours with a comparison with the presence of its receptor c-Kit proto-oncogene product (c-KIT). In normal skin, SCF was mainly observed in endothelial cells of blood vessels but not frequently in basal melanocytes, whereas c-KIT was predominantly localised in tissue mast cells. In benign neoplastic melanocytes (common melanocytic naevi), localisation of SCF and c-KIT was complementary: SCF was mostly found in dermal naevus cells while c-KIT was revealed in epidermal naevus cells, although the expression of the latter antigen was not frequent. Malignant melanoma cells showed less frequent expression of these antigens than those in benign lesions. Of five cultured melanoma cell lines, SCF was observed in only one, and c-KIT was not found in any melanoma cells. No quantitative or qualitative alterations assessed by Western blot analysis were induced in the presence of phenotypic modifiers (sodium butyrate and HMBA). Present data suggest that loss of SCF expression in neoplastic melanocytes is commonly associated with malignant transformation of pigment cells rather than loss of its receptor c-KIT.
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PMID:Immunohistochemical localisation of stem cell factor (SCF) with comparison of its receptor c-Kit proto-oncogene product (c-KIT) in melanocytic tumours. 749 98

v-ryk is the oncogene in the avian acute oncogenic retrovirus RPL30, its cellular counterpart, c-ryk, is described in this report. To avoid the confusion caused by another gene with the same name, we renamed v-ryk to be v-eyk, thereby changing the proto-oncogene's name to c-eyk. c-eyk is expressed highly in chicken spleen and moderately in many other tissues including embryonic tissues. Its cDNA is 3061 base pairs encoding a receptor-type protein tyrosine kinase (PTK) of 974 amino acids. Compared to c-Eyk, v-Eyk is a truncated PTK lacking the extracellular and transmembrane regions of c-Eyk in addition to two amino acid changes. c-Eyk has two C2-type Ig domains and two FN-III domains in its extracellular region, forming a new subfamily of receptor-type PTK together with UFO/Axl/Ark. As suggested by Ig/Fn-III domains in many cell adhesion molecules, this subfamily of PTK may mediate cell-cell interaction.
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PMID:The proto-oncogene of v-eyk (v-ryk) is a novel receptor-type protein tyrosine kinase with extracellular Ig/GN-III domains. 750 87


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