Decoy Promoters as Cancer Therapies

Science's STKE  15 Apr 2003:
Vol. 2003, Issue 178, pp. tw144
DOI: 10.1126/stke.2003.178.tw144

Aberrant gene expression is one characteristic of cancer biology. Leong et al. showed that inhibition of a particular transcription factor, signal transducer and activator of transcription 3 (STAT3), by application of a double-stranded oligonucleotide decoy decreased cell proliferation of cultured squamous cell carcinoma of the head and neck (SCCHN). The decoy oligonucleotide was based on the STAT3 response element hSIE, and an oligonucleotide with a single mutation that abolished STAT3 binding was used as a control. Only the decoy oligonucleotide inhibited expression of an hSIE-luciferase reporter gene, and in transfected cells, RNase protection assays showed that the decoy decreased transcription of the mRNA for the antiapoptotic Bcl-XL, a known target of STAT3. The growth inhibitory effects of the decoy oligonucleotide were limited to those cells with activated STAT3, in that normal (nontransformed) oral epithelial cell growth was not inhibited by the decoy. Thus, when aberrant signaling leads to excessive or inappropriate activation of a transcription factor, decoy promoter oligonucleotides may provide a strategy to block tumorigenic gene expression selectively.

P. L. Leong, G. A. Andrews, D. E. Johnson, K. F. Dyer, S. Xi, J. C. Mai, P. D. Robbins, S. Gadiparthi, N. A. Burke, S. F. Watkins, J. R. Grandis, Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth. Proc. Natl. Acad. Sci.U.S.A. 100, 4138-4143 (2003). [Abstract] [Full Text]