Toll-Like Receptor-9-Mediated Invasion in Breast Cancer
Annual rept. 15 Jun 2010-14 Jun 2011
ALABAMA UNIV IN BIRMINGHAM
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The focus of this research is to discern the structural and biophysical features of small deoxyoligonucleotides that have significant biological properties including the inducement of Toll-like receptor 9 TLR9 in the mediation of cellular invasion. Cell invasion metastasis is a significant problem in the control and treatment of breast cancer. Recent research from our laboratory has demonstrated enhanced cellular invasion in the MDA-MB-231 breast cancer cells by ODN-M362, a 25-base single-stranded CpG-containing deoxyoligonucleotide. Although the mechanisms for this induction is unknown, our studies reveal key insights into the structural and sequence requirements for DNA activation of this cellular invasion process. The deoxyoligonucleotides that are most effective in eliciting an invasion response have been shown to adopt stable structural motifs including stem-loops or hairpins or G-quadruplex structures. Sequence modifications have been designed to probe base sequence, structure, and stabilities that are required for initiating TLR-9 mediated cellular invasion. Our results demonstrate that these small deoxyoligonucleotides and the stability of their secondary structures play a pivotal role in eliciting the TLR9-induced invasion process.
- Anatomy and Physiology
- Medicine and Medical Research