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)

Murine papilloma cell lines 308 and SP-1 have been used as recipients for transfected oncogenes to investigate malignant conversion. These cell lines express an activated c-rasHa gene with a codon 61 mutation and produce squamous papillomas when transplanted as skin grafts onto nude mice. They are not tumorigenic by subcutaneous injection. Both papilloma cell lines were stably transfected with plasmid DNA containing either a rearranged murine plasmacytoma-derived c-myc (minus exon 1), adenovirus 5 E1A, FBJ v-fos or a human c-fos/FBJ v-fos chimera, using cotransfection with the neomycin resistance gene contained in pSV2neo to select for transformants. Southern and northern blotting analysis confirmed the uptake and expression of exogenous DNA in both G418-selected cell lines and in the derived tumors. Unlike the E1A- and myc-containing plasmids, both fos constructs caused malignant conversion in either cell line, as defined by the squamous cell carcinoma histology of tumors from grafted cells and the development of carcinomas after subcutaneous injection into athymic nude mice. Immunofluorescence analysis for specific keratin gene expression indicated that tumors derived by introduction of either of the fos oncogenes were devoid of staining for K1, a 67 kDa epidermal keratin that is expressed in papillomas but not in squamous carcinomas. Tumors from E1A, myc, or pSV2neo transfectants expressed K1, although in a focal distribution. The malignant phenotype induced by the fos oncogene constructs was not associated with the ability to form agar colonies in vitro or to express gamma-glutamyl transpeptidase in the tumors. Since both 308 and SP-1 were sensitive to the fos oncogene for malignant conversion and insensitive to E1A or myc, it is possible that fos may cooperate with the endogenous-activated c-rasHa gene to convert these cells to malignancy. However, since gamma-glutamyl transpeptidase activity is found in the majority of chemically induced mouse skin carcinomas that possess an activated c-rasHa gene, fos activation may not be a common pathway for spontaneous malignant conversion.
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PMID:Malignant conversion of murine squamous papilloma cell lines by transfection with the fos oncogene. 247 37

The effects of activated ras genes on a continuously dividing, nontransformed, rat liver-derived epithelial cell line have been studied. Genes have been introduced into cells in conjunction with a selectable drug (G418) resistance marker. Controls were obtained by transfecting with the drug resistance gene alone. Transformed, drug-resistance colonies were obtained on transfecting with ras plus resistance marker genes. They had an altered morphology, a tendency to pile up in culture, and showed anchorage-independent growth. They also were tumorigenic in nude mice with a short latent period. None of these properties was exhibited by nontransformed, drug-resistant colonies. Transformed clones were positive on histochemical staining for the enzyme gamma-glutamyltranspeptidase. A heterogeneity of gamma-glutamyltranspeptidase activity between cells of the same transformed clone was revealed by both histochemical and cytofluorographic assays. Nontransformed clones failed to stain histochemically for the enzyme. The fluorimetric determination of the specific activity of the enzyme showed consistently higher levels in transformed cells as compared to nontransformed, drug-resistant controls. The possible relationship between cell transformation and elevated levels of gamma-glutamyltranspeptidase is discussed.
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PMID:gamma-Glutamyltranspeptidase and the ras-induced transformation of a rat liver cell line. 286 25

The effects of gentamicin and G418 on the cellular function of LLC-PK1 epithelial pig kidney cells were investigated. Exposing the cells for 2 days to these aminoglycoside antibiotics inhibited the increase in cell-associated apical membrane enzyme activity (alkaline phosphatase, aminopeptidase, and gamma-glutamyltransferase). Kinetic analysis revealed that the maximal activity of alkaline phosphatase was reduced by these aminoglycosides. Both aminoglycosides inhibited [3H]leucine incorporation into microsomes prepared from LLC-PK1 cells. The LLC-PK1 cells transfected with DNA encoding aminoglycoside 3'-phosphotransferase II, designated T2000B, were resistant to G418 as assessed by colony formation assay and the number of floating dead cells and by assay of apical enzyme activity. After a 4-hr exposure to G418, [3H]leucine incorporation in the host LLC-PK1 cells was inhibited, whereas that in T2000B cells was relatively unaffected. Gentamicin inhibited [3H]leucine incorporation similarly in both cells. The inhibition of protein synthesis by aminoglycosides occurred earlier than that of apical enzyme activity. These findings suggest that the inhibition of protein synthesis by aminoglycoside antibiotics is a possible cause of the reduction in cell viability as well as the apical enzymes in LLC-PK1 cells.
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PMID:Cellular toxicity of aminoglycoside antibiotics in G418-sensitive and -resistant LLC-PK1 cells. 805 26