Kurzfassung

The mechanisms of cisplatin-resistance can divided into different groups: (i) mechanisms that prevent cisplatin from attacking DNA or that promote the repair of formed DNA adducts and (ii) mechanisms that block the induction of apoptosis and (iii) cell adhesion-mediated drug-resistance. Cell adhesion is mediated by a number of different proteins. In particular, members of the Rho family of small GTPases play a key role in the regulation of signaling pathways which are important for the...The mechanisms of cisplatin-resistance can divided into different groups: (i) mechanisms that prevent cisplatin from attacking DNA or that promote the repair of formed DNA adducts and (ii) mechanisms that block the induction of apoptosis and (iii) cell adhesion-mediated drug-resistance. Cell adhesion is mediated by a number of different proteins. In particular, members of the Rho family of small GTPases play a key role in the regulation of signaling pathways which are important for the regulation of cell adhesion. Data pointing to a function of Rho proteins in cell adhesion-mediated drug resistance to platin compounds are missing. Therefore, we plan to (i) examine the constitutive and cisplatin-induced levels of active Rho proteins in parental versus cisplatin-resistant cell variants (the variants gained cisplatin resistance via cell-adhesion mediated mechanisms) and (ii) to determine the role of Rho GTPases in cisplatin resistance by use of either pharmacological inhibitors (i.e. statins, isoprene transferases, ROK inhibitor) or by overexpression of wild-type, constitutively-active and dominant-negative Rho proteins. » weiterlesen» einklappen