Lipnik, K. and Greco, O. and Scott, S. and Knapp, E. and Mayrhofer, E. and Rosenfellner, D. and Gunzburg, W.H. and Salmons, B. and Hohenadl, C. (2006) Hypoxia- and radiation-inducible, breast cell-specific targeting of retroviral vectors. Virology, 349 (1). pp. 121-133. ISSN 0042-6822.
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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.
|Divisions:||Faculties > Science Technology and Medical Studies > Medway School of Pharmacy|
|Depositing User:||Simon Scott|
|Date Deposited:||12 Sep 2008 20:10|
|Last Modified:||14 Jan 2010 14:36|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/9712 (The current URI for this page, for reference purposes)|
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