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)

We have studied the ability of plasmids encoding a normal human myc protein to stimulate growth of primary rat embryo fibroblasts. We measured growth stimulation by the number of G418-resistant colonies obtained after co-transfection with plasmid pSV2neo and by the percentage of these colonies that grew in long-term culture (immortalization). Using a normal human myc gene, we detected a weak growth stimulation at the colony formation stage and a low frequency of immortalization. Replacement of the myc promoter by a heterologous promoter (mouse metallothionein I promoter) and deletion of the first non-coding exon led to a more efficient growth stimulation by both criteria. Thus, disregulation of c-myc is essential for an altered pattern of growth. Using zinc, a metallothionein inducer, we observed a slight increase in the growth rate of some transfectants, which can be measured by thymidine incorporation. However, the relative inefficiency of immortalization we observed suggests that either a high level of myc expression or participation of other genes is required for establishment in culture. Under our experimental conditions, we could not detect a transforming activity for the human myc gene and none of our myc-containing cell lines was tumorigenic in nude mice.
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PMID:Growth stimulation of rat primary embryo fibroblasts by the human myc gene. 374 60

A human esophageal cancer cell line (EC8712) expressing high-level Myc protein was infected with recombinant retroviral particles (pA-BD9) at a multiplicity of infection (MOI) 1:1. This viral particle contains a neomycin-resistant gene and a 1.53-kb antisense RNA spanning the 2nd exon and its flanking sequences of the human c-myc oncogene. The G418-resistant EC8712 clones showed an 86% inhibition of growth rate and morphological changes characteristic of terminal differentiation and apoptosis. A decrease of about 80% of Myc protein was also observed in these infected cells by ABC-ELISA assay. 12-24 h after the infection of EC8712 cells with pA-BD9 at a high viral particle concentration (MOI = 1:10), the integration of the extrinsic 1.53-kb antisense c-myc fragment into the cancer cell genome was evidenced by the Southern blot analysis. Northern blot analyses showed the expression of this antisense fragment and a decrease of the intrinsic c-myc expression by 74% in comparison with that of the parental EC8712 cells. Heterotransplants of the infected EC8712 cells into the nude mice revealed a substantial decrease in tumorigenicity and morphological changes characteristic of terminal differentiation and apoptosis. Primary monolayer cell cultures of normal epithelia derived from the fetal and adult esophagus mucosa were set as controls. No noticeable increase in c-myc expression was found in these cultures. Infection of these cells with the same recombinant viral particles neither affected the growth rate of the cells nor their normal morphology. Our experiments indicate that the drastic decrease of the over-expressed Myc protein in cancer cells may also be an entrance to one of many pathways leading to the terminal differentiation and programmed cell death.
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PMID:Abrupt reduction of c-myc expression by antisense RNA inducing terminal differentiation and apoptosis of a human esophageal cancer cell line. 762 99