Hypoxia- and radiation-inducible, breast cell-specific targeting of retroviral vectors

Lipnik, Karoline and Greco, Olga and Scott, Simon and Knapp, Elzbieta and Mayrhofer, Elisabeth and Rosenfellner, Doris and Gunzburg, Walter H. and 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. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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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
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > Medway School of Pharmacy
Depositing User: Simon Scott
Date Deposited: 12 Sep 2008 20:10
Last Modified: 24 Jun 2014 15:46
Resource URI: https://kar.kent.ac.uk/id/eprint/9712 (The current URI for this page, for reference purposes)
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