Triplex Inhibition of Progesterone Receptor

Triple helix formation between duplex DNA and oligonucleotides has been observed for over twenty years for synthetic polymers and more recently for genomic DNA. Triplex formation prevents the association of proteins with DNA including transcription factors and RNA polymerase. Triple helix formation at the promoter or within a structural gene has been shown to repress transcription, and cells growing in culture have been shown to take up single stranded oligonucleotides through the cell membrane. Further, uptake of triple helix-forming oligonucleotides directed against transfected promoter-reporter gene constructs has repressed transcription of reporter gene in cultured cells. We will use triple helix formation to repress the transcription of progesterone receptor. Since progesterone is one of a family of steroid hormones important in breast tissue growth and development, and other strategies of progesterone receptor repression have proven effective against some breast cancers, we believe this approach has potential therapeutic value against breast cancer.