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)

Transforming growth factor alpha (TGF alpha) is a growth factor produced by colon cancer cells which may function as an autocrine growth regulator. Therefore, the proliferation and transformation of colon cancer cells might be attenuated by blocking the production of endogenous TGF alpha. GEO cells, from a human colon carcinoma cell line that expresses TGF alpha and functional epidermal growth factor (EGF) receptors, were infected with a replication-defective, recombinant amphotropic retroviral expression vector containing the neomycin-resistance gene and a 435-bp ApaI-EcoRI coding fragment of the human TGF alpha cDNA oriented in the 3' to 5' direction under the transcriptional control of the heavy-metal-inducible mouse metallothionein I promoter. Following antibiotic selection, G418-resistant colonies were pooled and expanded into a cell line (GEO TGF alpha AS cells). A 50 to 70% inhibition in the production of secreted and cell-associated TGF alpha protein was observed in GEO TGF alpha AS cells that had been maintained in CdCl2-supplemented medium. Moreover, a growth inhibition of 70% and 50% was observed in CdCl2-treated GEO TGF alpha AS cells under anchorage-dependent and anchorage-independent culture conditions, respectively. In contrast, CdCl2 treatment of parental GEO cells had no significant effect upon these parameters. Our results suggest that TGF alpha may be involved in modulating the in vitro cell growth and transformation of human colon cancer cells that express both this growth factor and its cognate receptor.
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PMID:Infection with a transforming growth factor alpha anti-sense retroviral expression vector reduces the in vitro growth and transformation of a human colon cancer cell line. 833 3

Heat shock induces in cells the development of a transient state of thermotolerance thought to result from the induction of heat shock proteins. To assess directly whether a transient overexpression of one of these proteins, HSP27, can contribute to increased cellular resistance, mouse NIH/3T3 cells were cotransfected with a plasmid containing the Chinese hamster HSP27 gene under the control of the metallothionein promoter and a plasmid containing the neo gene. Stable transfectant cell lines were selected for resistance to the antibiotic G418. Analyses of several stable transfectant cell lines indicated that expression of Chinese hamster HSP27 could be selectively induced by exposure to 3 microM CdCl2, a concentration that had no effect on the induction of the endogenous heat shock proteins (HSP). In clone 15, the level of HSP27 increased steadily during the first day of exposure to CdCl2, from a concentration of 1 microgram/mg of total protein to 7 micrograms/mg. After withdrawal of CdCl2, the level of HSP27 returned to normal within the next 5 days. Accumulation of the Chinese hamster HSP27 was accompanied by a progressive development of thermoresistance that attained a level approaching heat shock-induced thermotolerance. After CdCl2 removal, thermal resistance and HSP27 decayed in a coordinated manner. In control cells transfected with the neo gene only, increased thermoresistance was not induced by 3 microM CdCl2; in these cells, an exposure to 20 microM CdCl2 was required to induce a level of thermoresistance comparable to that induced by 3 microM CdCl2 in clone 15. Elevated expression of HSP27 was accompanied by an increased stability of stress fibers during hyperthermia. The protein also partially prevented actin depolymerization during acute exposure to cytochalasin D and reduced cytotoxicity and growth inhibition of chronic exposures to the drug. The results indicated that accumulation of HSP27, as it occurs after a mild heat shock or other inducing treatments, is sufficient for acquisition of thermotolerance that may result in part from a stabilization of actin filaments.
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PMID:Induction of Chinese hamster HSP27 gene expression in mouse cells confers resistance to heat shock. HSP27 stabilization of the microfilament organization. 842 18

TIF3 (GenBank Accession Number AF 271072) is identified as a novel cadmium- responsive proto-oncogene. In order to determine whether the antisense TIF3 reverses the oncogenic potential of Cd-transformed BALB/c-3T3 cells or not, a stable expression system of CdCl2-transformed BALB/c-3T3 cells with the expression vector containing TIF3 cDNA in the antisense orientation using calcium phosphate and G418 selection protocols is firstly established. Then, the reversal of the oncogenic potential of these cells is tested by soft agar and nude mouse tumorigenicity assay. The results demonstrated that expression of the antisense TIF3 in the CdCl2-transformed BALB/c-3T3 cells results in reversal of the transformed phenotype of the cells. This is evidenced by a 25%-70% decrease in the number of anchorage-independent colonies growing on soft agar and the significant reduced tumorigenic potential of cells in nude mice compared with the corresponding controls. In addition to a significant delay in the onset of appearance of tumors, a significant reduction in size and a 50.8%-55.1% decrease in weight of the tumors are also observed in the mice injected with the TIF3 antisense expressing cells compared with the corresponding controls. The results indicate that antisense TIF3 mRNA expression reverses its oncogenic potential of Cd-transformed BALB/c-3T3 cells and may have therapeutic potential to cancer induced by cadmium.
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PMID:[Antisense TIF3 reverses the oncogenic potential of CdCl2-transformed BALB/c-3T3 cells]. 1260 33