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)

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

The ectopic expression of the small molecular weight heat shock protein HSP27 reportedly confers resistance to heat and other types of stress, but our recent findings indicated that it rendered human immortalized fibroblast cells (KMST-6) more sensitive to oxidative stress and caused irreversible growth arrest (Arata et al., 1995, J. Cell. Physiol., 163:458-465). To clarify the relationship between HSP27 and growth regulation, we investigated the effect of overexpression of HSP27 and its mutants on the growth potential of several cell lines. Mammalian expression vectors of the wild-type, hypophosphorylatable, or C-terminal deletion mutants of human HSP27 were constructed from the pRc/CMV plasmid that contained the neomycin-resistant gene. The plasmid was introduced into mouse fibroblasts (NIH 3T3), normal human fibroblasts (TIG-3), Chinese hamster ovary (CHO-K1), or mammary tumor cells (MCF-7), which were then selected in medium containing G418. The number of drug-resistant colonies was significantly decreased by transfection with the expression vector for wild-type HSP27 compared with vector alone, whereas the overexpression of HSP27 in CHO-K1 cells had essentially no effect. The expression vectors of an hypophosphorylatable mutant (pKSm, human HSP27 gene in which codons for Ser-15, -78, and -82 were converted to code for Gly by site-directed mutagenesis) as well as C-terminal deletion mutants in which 12-36 amino acid residues from the C-terminus were deleted had no significant effect on the colony-forming efficiency of NIH 3T3 cells. Cells isolated from G418-resistant colonies formed by transfection of NIH 3T3 cells with the HSP27 expression vector expressed no detectable levels of wild-type HSP27 and did not form stable clonal transformants expressing high levels of HSP27 from NIH 3T3 cells. In contrast, several clones expressing high levels of HSP27 were obtained from CHO-K1 cells transfected with the HSP27 expression vector. In KMST-6 clones expressing high levels of HSP27, the wild-type HSP27 formed aggregates with a mean molecular mass of about 200 kDa as determined by gel filtration, and the size of the oligomers changed with oxidative stress. On the other hand, the size of aggregates of HSP27 encoded by pKSm or C-terminal deletion mutants did not change. These observations indicated that the forced expression of wild-type HSP27 participates in inhibiting the growth of some cell types and that the inhibition may be associated with its phosphorylation and aggregation.
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PMID:Inhibition of colony formation of NIH 3T3 cells by the expression of the small molecular weight heat shock protein HSP27: involvement of its phosphorylation and aggregation at the C-terminal region. 901 81

Heat shock proteins (HSPs) play an important role in folding, intracellular localization and degradation of cellular proteins. However, the cellular role of HSP27 is not completely understood. The conflicting results have been reported regarding stress-induced nuclear translocation of HSP27. In this study, human breast cancer cells transiently and stably expressing HSP27-EGFP chimera were utilized to observe the intracellular localization of HSP27. The data show that the transient and stable expression of HSP27-EGFP displayed distinguishingly cellular localization. The nuclear translocalization of HSP27-EGFP was correlated with the presence of G418. Experiments carried out with different human breast cancer cell lines revealed clearly different distribution patterns of endogenous HSP27. The subcellular distribution of endogenous HSP27 appeared diffuse throughout the cytoplasm in MDA435 cells. In MCF-7 and SKBR3 cells, the accumulation of the protein was distinctly seen along the cell membrane and around nucleus. Moreover, the nuclear translocation of endogenous HSP27 was stimulated by G418 only in MDA435 cells, but not in MCF-7 and SKBR3 cells. Overexpression of HSP27 has been associated with resistance to cisplatin and doxorubicin. The correlation of the expression pattern of HSP27 with the drug resistance may need to be investigated. Further studies on the intracellular function of HSP27 may take into account its interaction proteins in the cells. It may provide useful information for the identification of sensitivity of carcinoma cells to the chemotherapeutic drugs and development of more specific agents to circumvent HSP27.
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PMID:Expression and distribution of HSP27 in response to G418 in different human breast cancer cell lines. 1673 62