Naslov
Cytoskeleton Alterations in Cisplatin-resistant Cells: The Role of Rho GTPases in Cisplatin Toxicity

Autori
Čimbora-Zovko, Tamara ; Ljubojević, Marija ; Sabolić, Ivan ; Mikac, Nevenka ; Fritz, Gerhard ; Osmak, Maja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Workshop on Endocytic Systems: Mechanism and Function / Riezman, Howard ; Stenmark, Harald - Ženeva : European Molecular Biology Organization (EMBO), 2007, 60-60

Skup
Workshop on Endocytic Systems: Mechanism and Function

Mjesto i datum
Villars-sur-Ollon, Švicarska, 18.09.2007. - 23.09.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
cisplatin; drug-resistance; Rac1; RhoB; endocytosis

Sažetak
Although acquired resistance to cisplatin represents a major obstacle to successful chemotherapy, the cellular mechanisms involved in this process are only partially known. We have developed cisplatin-resistant CA3ST and CK2 cells that show lower intracellular platinum accumulation than parental human laryngeal carcinoma HEp-2 cells. They also exhibit pronounced stress fibers and numerous focal contacts, in contrast to parental cells that display cortical actin organized in adhesion belt and few vinculin-containing focal adhesions. Therefore, we screened the expression of several Rho GTPases on both mRNA and protein level and found strong downregulation of RhoB mRNA in resistant cells. Cisplatin-resistant cells also had increased PKCα expression, Rac1 localized at plasma membrane and constitutive macropinocytosis. A single cisplatin treatment of HEp-2 cells induced formation of stress fibers, vinculin relocalization to focal contacts and Rac1 translocation to plasma membrane. Pretreatment with lovastatin decreased the level of membrane-bound Rho GTPases and increased fraction of apoptotic cells after cisplatin treatment, indicating Rho GTPases as possible mediators in cellular response to cisplatin. Therefore, with the use of inhibitors of various endosomal pathways, we are currently analyzing the specific mechanisms regulated by Rho GTPases that could be involved in cellular accumulation of cisplatin.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA