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

Lipnik, Karoline, Greco, Olga, Scott, Simon D., Knapp, Elzbieta, Mayrhofer, Elisabeth, Rosenfellner, Doris, Gunzburg, Walter H., Salmons, Brian, 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) (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)

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. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1016/j.virol.2005.12.038

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
DOI/Identification number: 10.1016/j.virol.2005.12.038
Subjects: Q Science
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Simon Scott
Date Deposited: 12 Sep 2008 20:10 UTC
Last Modified: 28 May 2019 13:46 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/9712 (The current URI for this page, for reference purposes)
Scott, Simon D.: https://orcid.org/0000-0002-8290-0461
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