In this context, the several fold change differences measured in the micro RNA cluster covering hsa miR selleckchem 371 373 is of interest. Based on our findings, hsa miR 371 373 expression in NTERA 2 R increased 4. 0 4. 7 fold relative to the paternal cisplatin sensitive NTERA 2 line, and even more in NCCIT R, relative to the cisplatin sensi tive paternal NCCIT cells, showing an 12. 0 16. 3 fold upregulation, table 1. Noteworthy, this micro RNA clus ter has been discussed in the context of the presence of wild type p53 in germ cell Inhibitors,Modulators,Libraries tumors, counteracting tumorigenesis by induction of senescence. By up regulation, the cluster prevents p53 driven cellular senescence via a plethora of target genes, e. g. NEO1 or LATS2, therefore leading to cell proliferation even in the presence of wild type p53.

Furthermore, this cluster has been described in cells exhibiting stem cell properties. Noteworthy, this cluster has recently been identified by other authors to be the most signifi cant differentially expressed Inhibitors,Modulators,Libraries microRNA in human germ cell tumors. Therefore, it appears a promising tar get for further analysis in germ cell tumors, e. g. by posttranscriptional silencing with siRNA, to examine the functional role of the cluster in altering gene expression and thereby elucidate its contribution to the development of cisplatin resistance. As already mentioned, there are other gene changes Inhibitors,Modulators,Libraries which have been discussed in the context of cisplatin resistance. The tumor suppressor Inhibitors,Modulators,Libraries p21, regulating transition through the cell cycle and acting downstream of p53, has already been associated with hsa miR520 belonging to the miR 106 302 family.

An increased Inhibitors,Modulators,Libraries expression of miR 106 302 family members inhibits the tumor suppressor p21 and rescues human mammary epithelial cells from Ras induced senescence. In our analysis, hsa miR520c as well as hsa miR520h were up regulated in NTERA 2 R NTERA 2 and NCCIT R NCCIT cell line pairs, which could point towards another mechanism counteracting senescence. In an in vitro model of cisplatin resistance of a squa mous cell carcinoma cell line, has miR 21 was found to be down regulated in cisplatin resistant cells. In our cell line pairs, significant down regulation of has miR 21 was observed in NCCIT R compared to sensitive NCCIT cells. Furthermore, hsa miR 146a, a microRNA targeting BRCA1, was the most highly up regulated microRNA in another in vitro model of cisplatin resis tance of the breast cancer cell line MCF7.

Similarly, both NTERA 2 R NTERA 2 and NCCIT R NCCIT showed up regulation in our analysis, yet to a lesser extent. However, has miR 221, which was also Trichostatin A TSA highly up regulated in cisplatin resistant MCF7 cells, was down regulated in NCCIT R and unaltered in the other two cell lines in our experiments, indicating that cispla tin resistance seems to be cell line or tumor type speci fic.