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Mega.co.nz offer the most popular and download the latest PC Games. Download and play games online.. Vir2 Electri6ity Mega.Overexpression of a putative topoisomerase II mediating the development of hyperdiploidy in human mammary carcinoma cells.
Antisense oligonucleotides have been used to demonstrate that mdr1 (multidrug resistance) gene expression is required for the development of human multidrug resistance (mdr) phenotype, and suggest the existence of other genes closely related to the mdr1 gene family (Jedd, M., Trivers, L.J., and Pearson, G.W. (1989) Oncogene 1, 431-437). Since topoisomerase II is intimately associated with DNA replication and mitosis, we hypothesized that topoisomerase II may also be required for the development of hyperdiploidy, a genetic event characteristic of multidrug-resistant human mammary carcinoma cells. To investigate this possibility, a plasmid construct containing the human topoisomerase II alpha isoform was transfected into the multidrug-resistant cell line MDA-MB-231/DOX/R and its drug-sensitive counterpart MDA-MB-231/con. This construct was engineered to produce increased levels of human topoisomerase II alpha in the presence of DOX (doxorubicin), a drug that is a substrate for topoisomerase II. Two dox-resistance selection criteria were used: drug resistance to doxorubicin in MDA-MB-231/DOX/R and the loss of mdr1 gene expression. The overexpression of the topoisomerase II alpha gene was estimated to be approximately 17-fold and 12-fold higher in MDA-MB-231/DOX/R cells than in its control counterpart MDA-MB-231/con, respectively. In addition, an approximately sixfold increase in topoisomerase II alpha mRNA level was observed in MDA-MB-231/DOX/R. These values correlate well with the presence of the hypersensitive mdr phenotype in MDA-MB-231/DOX/R cells, and the loss of mdr1 gene expression in MDA-MB-231/con cells. In both cell lines, there was an approximate twofold increase in the level of topoisomerase II alpha
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