Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High-level expression of the c-sis oncogene, which encodes the beta chain of platelet-derived growth factor, transforms immortalized rodent fibroblasts in vitro to a malignant phenotype. c-sis gene expression has been demonstrated in a variety of human tumors, although generally at levels much lower than those shown to transform cells in vitro. We examined the effect of lower levels of c-sis expression on the phenotype of NIH 3T3 fibroblasts. Clones with various levels of c-sis expression were generated by transfecting NIH 3T3 cells with a plasmid that expressed the human c-sis cDNA and the TN5 neomycin-resistance gene. G418-resistant clones, which expressed the c-sis cDNA, were selected and characterized. Alterations in the phenotype of the clones that expressed c-sis ranged from increased growth in soft agar to malignant tumor formation in nude and syngeneic mice. Increased levels of c-sis cDNA expression correlated with the acquisition of features of transformation in a dose-dependent manner and altered the cellular phenotype in a manner consistent with the progression of cells towards malignancy. These data support a model in which low levels of sis gene expression in tumors contribute to the acquisition of some features of transformation but require complementation by other genes or factors to produce a fully malignant phenotype.
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PMID:Malignant transformation of NIH 3T3 fibroblasts by human c-sis is dependent upon the level of oncogene expression. 132

CHO cells were transfected with plasmid pSM-1 (containing human c-sis cDNA) singly or co-transfected with pSV 2 neo DNA by calcium phosphate method. After low serum or G418 selection several cell lines with expression of platelet-derived growth factor (PDGF) were obtained. One among them, FB5, was of the highest PDGF expression and showed the following biological characteristics when compared with CHO cells: (1) a prominent change in morphology from spindle to round in shape: (2) increase of growth rate; (3) growth in low serum (2%) medium as a semisuspension culture; (4) growth on soft agar to larger colonies; (5) synthesis of PDGF in cytoplasm identified by immunofluorescent method; (6) the conditioned medium stimulated DNA synthesis of NRK cells; (7) RNA dot hybridization showing high transcription of PDGF mRNA; (8) southern blot showing integration of human c-sis gene was still stable after 7 months. These results indicated that intergration of exogenous c-sis gene and its high expression might cause CHO cells to high growth rate and even transformation. The establishment of this stable transformed cell line, FB5 is thought to be a good model for further study on the function of PDGF in cell growth control and cell transformation.
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PMID:[Expression of exogenous platelet-derived growth factor B chain gene in CHO cells]. 268 21

Early and transient expression of proto-oncogenes c-fos and c-myc is involved in the mitogenic response to PDGF (platelet-derived growth factor). We used DNA-mediated transfection to approach the role played by these genes in cell growth control by PDGF and in growth deregulation (neoplasia). Cloned pFBJ-2 (v-fos) and glucocorticoid-inducible mouse c-myc were co-transfected with a neo genetic marker to allow a neutral selection on the basis of resistance to the neomycin derivative geneticin G418. pFBJ-2 transfection was found to interfere with the number of G418-resistant (G418r) colonies. By using a v-fos-deleted pFBJ-2 construct, the deleterious effect was attributed to v-fos coding sequences. Cellular fos gene disruption, by homologous recombination with exogenous v-fos, is proposed as the basis for the deleterious effect. Co-transfection with MMTV-H3-c-myc effectively counteracts the negative effects of v-fos. Different from the parental line or single myc or fos transfectants, double myc/fos transfectants are morphologically transformed. Double transfectants still retain the PDGF requirement for growth in monolayer cultures.
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PMID:Generation of myc/fos transfectant Balb-3T3 cell lines. 325 75

Although PDGF is not a primary hematopoietic cytokine, effects in hematopoietic cell cultures have been reported. We recently described responses of multilineage hematopoietic precursors to PDGF. The effects were shown to be neutralized by antibody to IL-1 beta and mediated by marrow macrophages that expressed PDGF receptor RNA and responded to PDGF by upregulation of IL-1 RNA. The present study was performed to determine whether constitutive expression of PDGF by hematopoietic cells would have hematopoietic consequences in vivo. Retroviral vectors containing a PDGF-B gene were constructed and infected into normal marrow cells. Irradiated mice reconstituted with infected cells consistently developed a lethal myeloproliferative syndrome with anemia, neutrophilia and monocytosis, declining hematopoiesis in marrow with shift to the spleen, and extensive infiltration of immature hematopoietic cells into the parenchymal organs and connective tissues. In addition to PDGF, the retroviral constructs expressed a neo resistance marker. Phenotypic expression patterns in fibroblasts and in hematopoietic colony-forming cells in vitro were consistent with a significant degree of interaction between the two expressed inserts. Moreover, selection of infected cells for G418 resistance significantly reduced not only the number of infected reconstituting cells but also the intensity of the evoked syndrome in vivo. The observations have important implications for projected gene therapy protocols, and identify a novel potential pathway to myeloproliferative disease.
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PMID:Overexpression of PDGF-B in murine hematopoietic cells induces a lethal myeloproliferative syndrome in vivo. 830 75

Human phosphatase and tensin homolog (hPTEN) gene was expressed in vascular smooth muscle cells (VSMCs) to study its effect on VSMC proliferation induced in platelet-derived growth factor (PDGF) conditioned medium. After G418 selection, MTT assay was conducted to examine transfected VSMC proliferation induced in human PDGF conditioned medium. We successfully constructed eukaryotic expression vector pcDNA4/myc-His-PTEN and transferred into VSMC cells. We report that in vitro proliferation of VSMC was inhibited in PTEN transfected VSMCs induced in PDGF conditioned medium. RT-PCR and Western blot results indicated significantly high levels of protein kinase B-PKB and nuclear factor kappa B mRNA and protein, respectively, in PDGF group as compared with the control group.
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PMID:Effect of recombinant hPTEN gene expression on PDGF induced VSMC proliferation. 2489 5