Scoparone Further resolution of the differences among these results might be best facilitated by genome-wide transcriptional array analysis. In this study, we report successful establishment of two chondrosarcoma cell lines resistant to ET-743 or PM00104. We then asked how the gene expression levels related to differences in drug resistance in these two cell lines. We used Affymetrix Gene Chip U133 Plus 2 to examine genome-wide expression of RNA transcripts. As compared with several studies using smaller scale gene array, this array completely covers the entire human genome with over 47,000 transcripts. We validated the gene array results for the genes with the most significant changes with real-time RTPCR. As expected, there are a large number of transcriptional changes associated with in vitro acquired resistance to ET-743 and PM00104. Indeed, about 5% to 10% of transcripts are over-expressed or under-expressed in the resistant cell lines CS-1/ER and CS-1/PR as compared to the sensitive parental cell line. In the list of top 20 over expressing genes for both CS-1/ER and CS-1/PR, the same three zinc finger protein genes, ZNF93, ZNF43 and ZNF568 were all identified. These genes have not been previously associated with drug resistance. Realtime PCR confirmed ZNF93 and ZNF43 are consistently over expressed in these resistant cell lines. Preliminary evaluation of ZNF93 confirms that its expression is associated with the multidrug-resistant phenotype in additional cell lines. ZNF93 gene expression was also shown to be increased in ET-743 resistant Ewing��s sarcoma cell line and in the cisplatinresistant ovarian cancer cell line but not in the paclitaxel resistant cell lines nor in the paclitaxel resistant breast cancer cell line, suggesting a fundamentally different mechanism for paclitaxel resistance from ET-743 or PM00104 resistance. Functional analysis of ZNF93 provides some Benzoylmesaconine insight into the epigenetics of ET-743 and PM00104 resistance and might be of use in revealing targets for overcoming drug resistance. Inhibition of ZNF93 using siRNA could partially reverse PM00104, ET-743 and cisplatin resistance in CS-1/PR and A2780cp cells.