Project description:We exposed Salmonella TA100 cells to 3 concentrations of MX that produced a linear concentration-response for mutagenesis with little cell killing. We measured mutagenesis, survival, and global gene expression. We used custom-spotted glass slides as our microarray platform and identified genes whose expressions were altered by MX treatment using three methods: (1) a Bayesian t-test, (2) an operon analysis that assumes if one gene in an operon is differentially expressed then all genes in that operon are differentially expressed, and (3) a monotonic-expression response to increasing doses of MX. The resulting list of genes was analyzed for functional and KEGG pathway representation. Keywords: dose response
Project description:Breast cancer is a leading cause of cancer-related deaths among women in the Western world. Anthracyclines, including doxorubicin (DOX), along with taxanes, cyclophosphamide and platinum compounds are the main chemotherapeutic agents applied for breast cancer treatment. However, chemoresistance is the major cause of the disease progression following chemotherapy. Drug resistance can be either inherent or acquired during the treatment, but most possibly the interaction of both mechanisms drives the rapid development of treatment refractory cancer. In the present study, the mechanisms of acquired cellular chemoresistance were studied in breast cancer cell line MX-1 exposed to gradually increasing concentration of the chemotherapeutic compound DOX (MX-1/D). Nongenotoxic phosphorganic compound tetraphenylphosphonium cation (TPP+) – a potent substrate and activator for ABCB1 transporter – was used in the cell line model of intrinsic chemoresistance (MX-1/T). Finally, DOX highly resistant cell subline was derived from ABCB1-activated, TPP+ pretreated cells (MX-1/TD). Chemoresistance in all cell sublines was closely associated with the EMT, and the ABCB1 hyperexpression was a possibly trigger of this process.
