Lipnik, Karoline, Greco, Olga, Scott, Simon, Knapp, Elzbieta, Mayrhofer, Elisabeth, Rosenfellner, Doris, Günzburg, Walter H., Salmons, Brian and Hohenadl, Christine (2006) Hypoxia- and radiation-inducible, breast cell-specific targeting of retroviral vectors. Virology, 349 (1). pp. 121-133. ISSN 0042-6822 (doi:10.1016/j.virol.2005.12.038)

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Abstract

To facilitate a more efficient radiation and chemotherapy of mammary tumours, synthetic enhancer elements responsive to hypoxia and ionizing radiation were coupled to the mammary-specific minimal promoter of the murine whey acidic protein (WAP) encoding gene. The modified WAP promoter was introduced into a retroviral promoter conversion (ProCon) vector. Expression of a transduced reporter gene in response to hypoxia and radiation was analysed in stably infected mammary cancer cell lines and an up to 9-fold increase in gene expression demonstrated in comparison to the respective basic vector. Expression analyses in vitro, moreover, demonstrated a widely preserved mammary cell-specific promoter activity. For in vivo analyses, xenograft tumours consisting of infected human mammary adenocarcinoma cells were established in SCID/beige mice. Immunohistochemical analyses demonstrated a hypoxia-specific, markedly increased WAP promoter-driven expression in these tumours. Thus, this retroviral vector will facilitate a targeted gene therapeutic approach exploiting the unique environmental condition in solid tumours.

Item Type:	Article
Uncontrolled Keywords:	CArG element, hypoxia responsive element, promoter conversion, retroviral vector, breast cell-specific expression targeting, breast cancer xenografts, mouse model
Subjects:	R Medicine > RS Pharmacy and materia medica
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science > Medway School of Pharmacy
Related URLs:	Publisher Organisation
Last Modified:	28 Jun 2012 09:55
URI:	http://gala.gre.ac.uk/id/eprint/8432

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