1. ¹James Buchanan Brady Urology Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
2. ²Department of Urology, Chang Gung Memorial Hospital, Kweishan, Taoyun, Taiwan
3. ³Department of Neurosurgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA
4. ⁴Department of Urology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
5. ⁵Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

Correspondence: Ronald Rodriguez, James Buchanan Brady Urology Institute, Johns Hopkins University School of Medicine, Marburg Room 205, 600 North Wolfe Street, Baltimore, Maryland 21287-2101, USA. E-mail: rrodrig@jhmi.edu

The first two authors contributed equally to this work.

Received 31 January 2007; Accepted 30 April 2007; Published online 12 June 2007.

Abstract

Conditionally replication competent adenoviruses (CRAds) represent one of the most intensely studied gene therapy strategies for a variety of malignancies, including prostate cancer. These viruses can be generated by placing a tissue or cancer-specific promoter upstream of one or more of the viral genes required for replication (e.g., E1A, E1B). We report here that E1A inhibits androgen receptor (AR) target gene induction and, correspondingly, activated AR inhibits adenoviral replication. This mutual inhibition appears to be an indirect effect, possibly through competition for shared transcriptional co-activators. The net effect is that the oncolytic effect of prostate-specific CRAds is attenuated by these interactions. Fusion of the E1A to AR ameliorates this inhibition, while enhancing specificity. These findings have significant implications in the development of prostate-specific CRAd therapies.