RHABDOMYOSARCOMA-SPECIFIC EXPRESSION OF THE HERPES-SIMPLEX VIRUS THYMIDINE KINASE GENE CONFERS SENSITIVITY TO GANCICLOVIR

We examined a panel of cell lines for the expression of the myogenic p roteins myoD and myogenin. High level expression of both proteins was seen in rhabdomyosarcoma (RMS). To determine whether promoter elements from these genes could direct RMS cell-specific expression, we genera ted reporter constructs containing one or two copies of the myoD enhan cer coupled to the SV40 promoter. Transient transfection reporter assa ys confirmed the selective expression of beta-galactosidase (beta-gal) in 8 RMS cell lines. In contrast, very low expression from the myoD e nhancer/SV40 promoter was detected in four non-RMS cell lines. To dete rmine whether the hybrid promoter could elicit RMS-specific cytotoxici ty, a mammalian expression vector containing the herpes simplex virus thymidine kinase (HSVtk) under control of the hybrid myoD enhancer/SV4 0 promoter was constructed. After electroporation into several cell li nes, selective RMS cell kill was observed after treatment with gancicl ovir. These data suggest that in vivo tumor-specific expression of HSV tk from the myoD enhancer/SV40 promoter may provide an alternative to current chemotherapy.