1. ¹Division of Human Gene Therapy, Department of Medicine, Pathology, and The Gene Therapy Center, University of Alabama at Birmingham, Birmingham AL, USA
2. ²Division of Gynecologic Oncology, University of Alabama at Birmingham, Birmingham AL, USA
3. ³Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA

Correspondence: Dr David T Curiel, Division of Human Gene Therapy, Gene Therapy Center, BMR II 508, 2172, 901 19th Street S, University of Alabama at Birmingham, Birmingham, AL 35291, USA. E-mail: david.curiel@ccc.uab.edu

Received 4 September 2003; Published online 12 March 2004.

Abstract

It has been demonstrated that survivin, a novel member of the inhibitor of apoptosis (IAP) protein family, is expressed in human cancers but is undetectable in normal differentiated tissues. We employed a recombinant adenoviral vector (reAdGL3BSurvivin) in which a tumor-specific survivin promoter and a luciferase reporter gene were inserted into the E1-deleted region of adenovirus vector. Luciferase activity was measured in both multiple tumor cell lines and two primary melanoma cells infected with reAdGL3BSurvivin. Human fibroblast and mammary epithelial cell lines were used as negative controls. A reAdGL3CMV, containing the CMV promoter and luciferase gene, was used as a positive control to normalize the luciferase activity generated by the survivin promoter. Our data revealed that the survivin promoter showed high activity in both established tumor cell lines and the primary melanoma cells. In contrast, the in vivo studies indicated that the activities of survivin promoter were extremely low in the major mouse organs. The survivin promoter appears to be a promising tumor-specific promoter exhibiting a "tumor on" and "liver off" profile, and therefore, it may prove to be a good candidate for transcriptional targeting of cancer gene therapy in a wide variety of tumors.