BREAST-CANCER SELECTIVE GENE-EXPRESSION AND THERAPY MEDIATED BY RECOMBINANT ADENOVIRUSES CONTAINING THE DF3 MUC1 PROMOTER/

The high molecular weight mucin-like glycoprotein, DF3 (MUC1), is over expressed in the majority of human breast cancers, Here we demonstrate that replication defective recombinant adenoviral vectors, containing the DF3 promoter (bp -725 to +31), can be used to express beta-galact osidase (Ad.DF3-beta gal) and the herpes simplex virus thymidine kinas e (HSV-tk) gene (Ad.DFS-tk) in DF3 positive breast carcinoma cell line s, In vivo experiments using breast tumor implants in nude mice inject ed with Ad.DF3-beta gal demonstrated that expression of the beta-galac tosidase gene is limited to DF3-positive breast cancer xenografts, Mor eover, in an intraperitoneal breast cancer metastases model, we show t hat i.p. injection of Ad.DF3-tk followed by GCV treatment results in i nhibition of tumor growth, These results demonstrate that utilization of the DF3 promoter in an adenoviral vector can confer selective expre ssion of heterologous genes in breast cancer cells in vitro and in viv o.