Increased Adenovirus Type 5 Mediated Transgene Expression Due to RhoB Down-regulation

Majhen, Dragomira; Stojanović, Nikolina; Vukić, Dunja; Pichon, Chantal; Leduc, Chloe; Osmak, Maja; Ambriović-Ristov, Andreja (2014) Increased Adenovirus Type 5 Mediated Transgene Expression Due to RhoB Down-regulation. PLoS ONE, 9 (1). e86698/1-e86698/11. ISSN 1932-6203

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Abstract

Adenovirus type 5 (Ad5) is a non-enveloped DNA virus frequently used as a gene transfer vector. Efficient Ad5 cell entry depends on the availability of its primary receptor, coxsackie and adenovirus receptor, which is responsible for attachment, and integrins, secondary receptors responsible for adenovirus internalization via clathrin-mediated endocytosis. However, efficacious adenovirus-mediated transgene expression also depends on successful trafficking of Ad5 particles to the nucleus of the target cell. It has been shown that changes occurring in tumor cells during development of resistance to anticancer drugs can be beneficial for adenovirus mediated transgene expression. In this study, using a study model consisting of a parental cell line, human laryngeal carcinoma HEp2 cells, and a cisplatin-resistant clone CK2, we investigated the cause of increased Ad5-mediated transgene expression in CK2 as compared to HEp2 cells. We show that the primary cause of increased Ad5- mediated transgene expression in CK2 cells is not modulation of receptors on the cell surface or change in Ad5wt attachment and/or internalization, but is rather the consequence of decreased RhoB expression. We show that RhoB plays an important role in Ad5 post-internalization events and more particularly in Ad5 intracellular trafficking. To the best of our knowledge, this is the first study showing changed Ad5 trafficking pattern between cells expressing different amount of RhoB, indicating the role of RhoB in Ad5 intracellular trafficking.

Item Type:	Article
Uncontrolled Keywords:	adenovirus; RhoB; cisplatin resistance; intracellular trafficking
Subjects:	NATURAL SCIENCES > Biology
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Stanični odgovor na citotoksične spojeve i razvoj otpornosti [34303] Maja Osmak 098-0982913-2748 MZOS Povećanje transdukcije adenovirusnih vektora i otpornost stanica na citostatike [173311] Andreja Ambriović Ristov 098-0982913-2850 MZOS
Depositing User:	Dragomira Majhen
Date Deposited:	09 Jul 2015 08:19
URI:	http://fulir.irb.hr/id/eprint/2041
DOI:	10.1371/journal.pone.0086698

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