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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently detected a novel activated oncogene by transfection analysis on NIH 3T3 cells in five out of 20 primary human thyroid papillary carcinomas and in the available lymph node metastases. We designated this transforming gene PTC (for papillary thyroid carcinoma). Here we describe the molecular cloning and sequencing of the gene. The new oncogene resulted from the rearrangement of an unknown amino-terminal sequence to the tyrosine kinase domain of the ret proto-oncogene. This gene rearrangement was detected in all of the transfectants and in all of the original tumor DNAs, but not in normal DNA of the same patients, thus indicating that this genetic lesion occurred in vivo and is specific to somatic tumors. Moreover, the transcript coded for by the fused gene was detected in an additional PTC-positive human papillary carcinoma for which mRNA was available.
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PMID:PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. 240 25

An antibody against the human epidermal growth factor receptor (EGF), capable of activating its tyrosine kinase has been produced. Antibody 2913 recognizes only the cytoplasmic portion of the EGF receptor in A431 carcinoma cells, in normal human fibroblasts, and in a variety of other human tumor cell lines (Xu, Y.-A., Richert, N., Ito, S., Merlino, G. T., and Pastan, I. (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 7308-7313). Indirect immunofluorescence and electron microscopy show that the antibody binds to intact cells only after membrane permeabilization. Moreover the antibody immunoprecipitates the v-erb-B gene product in avian myeloblastosis virus-infected cells but does not recognize the secreted form (105 kDa) of the A431 cell EGF receptor which lacks the cytoplasmic domain. Antibody 2913 activates the EGF receptor kinase in solubilized A431 membranes causing autophosphorylation on tyrosine residues only. Tryptic peptide maps suggest that antibody 2913 and EGF stimulate phosphorylation of the same amino acid residues. By electron microscopy, the cytoplasmic portion of the receptor was followed throughout its endocytotic pathway. The results show that the kinase domain is rapidly degraded in lysosomes with no accumulation in the cytoplasm or in the nucleus.
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PMID:Functional studies on the EGF receptor with an antibody that recognizes the intracellular portion of the receptor. 241 17

The relative abundance of pp60c-src molecules associated with polyomavirus (Py) middle tumor antigen (MTAg) and the relative abundance of MTAg associated with pp60c-src in a variety of Py-transformed rat cells was determined by quantitative immunoblot analyses which detect pp60c-src or Py MTAg. The results demonstrate that approximately 5 to 10% of the total immunoprecipitable pp60c-src molecules in Py-transformed rat cells are stably associated with MTAg and have elevated protein kinase activities. In these same cells, it was found that approximately 10 to 15% of the detectable MTAg molecules are stably associated with pp60c-src. Other results presented in this report demonstrate that approximately 50 to 75% of the total MTAg-associated cellular tyrosine kinase activity potentially represents the enzymatic activity of pp60c-src, while the remaining 25 to 50% represents the activity of other cellular tyrosine kinases. Our results also show that most pp60c-src molecules associated with Py MTAg do not possess electrophoretic mobilities that are altered from those of pp60c-src molecules not associated with MTAg or pp60c-src molecules obtained from normal rodent cells.
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PMID:Analysis of middle tumor antigen and pp60c-src interactions in polyomavirus-transformed rat cells. 244 13

Inoculation of newborn mice with the murine polyoma (Py) virus leads to tumor formation in a wide range of tissues. In order to investigate viral oncogenesis, we generated transgenic mice carrying either the Py large T antigen (LT) gene or the Py middle T antigen (MT) gene linked to Py early region regulatory sequences. While Py LT mice exhibit no phenotype, Py MT mice develop multifocal tumors of the vascular endothelium. These hemangiomas are lethal to the animals and can be passaged in vivo. Transgene RNAs and protein are present in both hemangiomas and the testes of these mice, and the Py middle T protein in both tissues is complexed to a cellular tyrosine kinase. The expression of complexed middle T protein in both tumorigenic endothelial cells and unperturbed testes implies that endothelial cells may be particularly susceptible to the action of the middle T oncogene. These observations indicate that Py middle T disrupts the normal strict controls on vascular growth, and suggest that Py MT transgenic mice will provide a model for studying the control of angiogenesis.
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PMID:Endothelial cell tumors develop in transgenic mice carrying polyoma virus middle T oncogene. 244 89

Tumor-derived Syrian hamster embryo (SHE) cell lines, induced in vitro by treatment with chemical carcinogens, contained increased levels of pp60c-src kinase activity compared to preneoplastic parental cell lines and normal SHE cells. The increased kinase activity did not result from an increase in the pp60c-src content of the SHE cell lines, but represented a 4-11 fold increase in pp60c-src kinase specific activity. Both the extent of phosphorylation and the velocity of pp60c-src phosphotransferase activity were increased in the tumor-derived cell lines. SHE cell lines producing chicken pp60c-src were isolated following co-transfection with plasmids bearing the chicken c-src and neoR genes. Chicken pp60c-src expressed in an asbestos-transformed, tumor-derived cell line showed an approximate 3-fold activation of tyrosine kinase activity compared to chicken pp60c-src expressed in the preneoplastic cell line. We suggest that these results indicate that activation of pp60c-src is mediated by trans-acting cellular factors present in the tumor-derived cells. Analysis of pp60c-src in normal SHE cells, preneoplastic cell lines and tumor-derived cell lines showed no alteration in the phosphorylation of tyr-527 or tyr-416, two tyrosine residues whose phosphorylation states have been associated with modulation of kinase activity. These studies indicate that the neoplastic progression of cells may be accompanied by the activation of proto-oncogene products, such as the pp60c-src tyrosine kinase, by mechanisms that may not directly involve genetic alteration of the proto-oncogene DNA sequence.
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PMID:Activation of pp60c-src tyrosine kinase specific activity in tumor-derived Syrian hamster embryo cells. 245 99

Treatment of normal Syrian hamster embryo (SHE) cells in vitro with various chemical carcinogens results in transformed preneoplastic cell lines. Continued passage of these preneoplastic cells gives rise to rare variant cells with enhanced capacity for tumorigenic growth. We have previously shown that tumor-derived SHE cell lines contain an activated proto-oncogene product, pp60c-src. Here we demonstrate that tumor-derived SHE cell lines contain several novel tyrosine phosphoproteins in addition to those found in preneoplastic parent cell lines. A correlation was observed between the activation of endogenous pp60c-src tyrosine kinase specific activity and the presence of new phosphotyrosine-containing proteins. Tyrosine phosphoproteins of approximate Mr 81 kilodaltons (kDa), 55 kDa, and 39 kDa were noted in different tumor-derived cell lines. The 81 kDa and 55 kDa proteins were membrane-associated phosphoproteins, whereas the 39 kDa protein was predominantly cytosolic. Additional signature tyrosine phosphoproteins in individual tumor-derived cell lines apparently were unique to the particular inducing carcinogen or target cell. These studies indicate that during chemical carcinogenesis, activation of the tyrosine kinase proto-oncogene protein pp60c-src coincides with the appearance of novel tyrosine phosphorylations.
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PMID:Novel tyrosine phosphorylations accompany the activation of pp60c-src during chemical carcinogenesis. 246 23

The human c-erbB-2 gene encodes a growth factor receptor-like protein that is highly homologous to the epidermal growth factor (EGF) receptor. Previous studies have shown that the c-erbB-2 gene is preferentially expressed in fetal epithelial cells, suggesting that the ligand of the gene product controls the growth of these cells. Molecular analysis of the c-erbB-2 promoter region revealed three regulatory systems: they are a typical set of CCAAT and TATA boxes, GC boxes, and Myb binding sites. Binding of the c-myb and B-myb gene products to the promoter region seems to down-regulate the c-erbB-2 mRNA synthesis. Elevated expression of this gene is often associated with adenocarcinomas such as breast cancers and stomach cancers and is correlated with the spread of the former. Involvement of the c-erbB-2 gene in the tumor development is further demonstrated by induction of B-lymphomas in transgenic mice carrying normal or mutated forms of this c-erbB-2 gene. In addition, the transforming potential of the c-erbB-2 gene is closely correlated with elevated tyrosine kinase activity of the gene product, which is negatively regulated by its carboxy-terminal sequence of about 230 amino acid residues.
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PMID:Regulation of expression and transforming ability of the c-erbB-2 gene. 257 38

Increased -GlcNA beta-6 Man alpha 1-6 Man beta 1- branching of Asn-linked oligosaccharides has been observed in a number of rodent and human tumor cell lines and the structures have been correlated with enhanced metastatic potential of murine tumor cells. Here we have compared the malignant potential and levels of beta 1-6-branched oligosaccharides in rat 2 fibroblast transfected with the cytoplasmic tyrosine kinase v-fps/fes, the activated GTPase T24 H-ras, and the nuclear oncogene c-myc. Rat2 cells transfected with activated c-myc were non-tumorigenic in nude mice and did not show elevated levels of beta 1-6 branched oligosaccarides, whereas transfectants carrying H-ras or v-fps were tumorigenic and generally exhibited metastatic potential which was associated with increased beta 1-6 branching. Enhanced expression of beta 1-6 branched oligosaccharides did not correlate with increased ratios of UDP-HexNAc to UDP-Hex, but was accompanied by elevated GlcNAc-transferase V activity, increased sensitivity of the cells to the toxic effects of leukoagglutinin, and an altered intracellular distribution of beta 1-6-branched oligosaccharides as visualized by fluorescent lectin staining. These results provide information on the quantitative and qualitative relationships between oncogene expression and cellular glycosylation and suggest that the ability of an oncogene to confer metastatic potential may be related to its ability to induce increased branching of Asn-linked oligosaccharides.
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PMID:Oncogenes conferring metastatic potential induce increased branching of Asn-linked oligosaccharides in rat2 fibroblasts. 266 6

Oncogenes are one of the most important structures in tumor pathogenesis. Both extracellular (growth factors, membrane receptors, tyrosine kinase) and intracellular (phospholipids and nuclear phosphoproteins) signals are involved in cell proliferation. New data are becoming available that will allow a better understanding of tumor etiology.
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PMID:[Recent findings on the role of oncogenes in neoplasms]. 266 63

EGF was used to stimulate a chimeric receptor consisting of the epidermal growth factor receptor (EGFR) extracellular, transmembrane, and protein kinase C-substrate domains linked to the intracellular tyrosine kinase and carboxyl terminal domains of the rat neu protein in NIH/3T3 cells. EGF-induced rapid and delayed morphological changes consisted of membrane ruffling, increased pinocytosis, extension of lamellar actin-containing footpads at the cell periphery and partial reorganization of the actin stress fibers in the cells. EGF bound to the cells was rapidly internalized in a complex with the EGFR/neu protein, as shown by loss of EGF binding and EGFR antigens from the cell surface. The movement of the EGFR/neu protein was followed with indirect immunofluorescence into a vesicular intracellular compartment using antibodies against both EGFR and neu protein domains. Metabolic labeling and pulse-chase experiments indicated that the receptor was degraded soon after its internalization. EGF treatment also induced the junB transcription factor mRNA and a dose-dependent stimulation of DNA synthesis in cultures expressing the chimeric receptor. The tumor promoter TPA led to a transient loss of cell surface receptors and prevented EGF stimulation of DNA synthesis but did not completely abolish junB mRNA induction or increase degradation of the chimeric receptor. These results show that the chimeric EGFR/neu receptor undergoes typical downregulation upon ligand binding and TPA pretreatment and is capable of transducing an EGF-induced mitogenic signal.
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PMID:Receptor downregulation and DNA synthesis are modulated by EGF and TPA in cells expressing an EGFR/neu chimera. 269 32


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