Transcription factor decoy (TFD) in breast cancer research and treatment.

Abstract

Synthetic oligonucleotides have recently been the object of many investigations aimed to develop sequence-selective compounds able to modulate, either positively or negatively, transcription of eukaryotic and viral genes. Alteration of transcription could be obtained by using synthetic oligonucleotides mimicking target sites of transcription factors (the transcription factor decoy -TFD- approach). This could lead to either inhibition or activation of gene expression, depending on the biological functions of the target transcription factors. Since several transcription factors are involved in tumor onset and progression, this issue is of great interest in order to design anti-tumor compounds. In addition to oligonucleotides, peptide nucleic acids (PNA) can be proposed for the modulation of gene expression. In this respect, double-stranded PNA-DNA chimeras have been shown to be capable to exhibit strong decoy activity. In the case of treatment of breast cancer cells, decoy oligonucleotides mimicking CRE binding sites, promoter region of estrogen receptor alpha gene, NF-kB binding sites have been used with promising results. Therefore, the transcription factor decoy approach could be object of further studies to develop protocols for the treatment of breast cancer. In the future, transcription factors regulating cell cycle, hormone-dependent differentiation, tumor invasion and metastasis are expected to be suitable targets for transcription factor decoy.