A Critical Dose of Doxorubicin Is Required to Alter the Gene Expression Profiles in MCF-7 Cells Acquiring Multidrug Resistance

摘要: Cellular mechanisms of multidrug resistance (MDR) are related to ABC transporters, apoptosis, antioxidation, drug metabolism, DNA repair and cell proliferation. It remains unclear whether the process development is programmable. We aimed study gene expression profiling circumstances in MCF-7 during MDR development. Eleven sublines with incremental doxorubicin were established as a valued tool progression. marker P-gp was overexpressed only cells termed MCF-7/ADR-1024 under selection dose approaching 1024 nM. authentic MCF-7/ADR shared common features morphology ploidy status. down regulated genes BRCA1/2 wild type p53, apoptosis-related Bcl-2 epithelial-mesenchymal transition (EMT) epithelial E-cadherin. While detoxifying enzymes glutathione-S transferase-π protein kinase C-α up-regulated. The involving EMT mesenchymal formation also overexpressed, including N-cadherin, vimentin E-cadherin transcription reppressors Slug, Twist ZEB1/2. PI3K/AKT inhibitor wortmannin suppressed mdr1. Mutant p53 deletion at codons 127-133 markedly appeared well. In addition, exerted CSC-like surface CD44 high/CD24 low form mammospheres. Overall, results suggest that arises owing turn on/off or mutation involved repair, enzymes, transporters turning point (1.024 μM challenge). Behind this point, no obvious alterations found most tested genes. Selection for may importantly attribute propagation population presenting invasive properties resistance. thereby two models induction Model 1: cells. 2: Mutations gain-of Either model 1 2 requires alter regulation.