Premium
EXPLORING DOUBLE‐STRANDED RNA AS A POSSIBLE CHEMOTHERAPEUTIC AGENT
Author(s) -
Schramm Danielle N.,
Lepine Sandrine,
Bell Jessica K.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.526.5
Subject(s) - rna silencing , mda5 , tlr3 , biology , receptor , rig i , protein kinase r , microbiology and biotechnology , innate immune system , pattern recognition receptor , rna , gene expression , signal transduction , toll like receptor , rna interference , gene , genetics , protein kinase c , mitogen activated protein kinase kinase
Pattern recognition receptors (PRRs) function in the innate immune system to alert the host to pathogenic components. Double‐stranded RNA (dsRNA), viral genomic material or a viral replication intermediate, trigger the PRRs toll‐like receptor 3 (TLR3), retinoic acid‐inducible gene I (RIG‐I), melanoma differentiation‐associated gene 5 (MDA5), and dsRNA‐dependent protein kinase receptor (PKR). Previous studies have reported that dsRNA stimulation induced TLR3‐dependent apoptosis. Objectives Examine 786‐O, OVCAR‐3, OVCA‐420, SKOV‐3, DOV‐13, CAOV‐3 cells for dsRNA receptor expression and determine dsRNA‐induced response. Methods PRR expression was confirmed by RT‐PCR. Expression levels were determined via qPCR. Apoptotic response to dsRNA stimulation was measured by Hoechst staining 48h post‐stimulation. Results 786‐O, SKOV‐3 and DOV‐13 show no response to dsRNA. RT‐PCR analysis showed that cell lines contained mRNA for all dsRNA receptors. qPCR showed a significant increase in PRR expression in those cell lines that underwent dsRNA‐induced apoptosis. Conclusions Four dsRNA receptors are present in our cell lines. dsRNA receptor expression does not correlate with dsRNA induced apoptosis, but increased dsRNA receptor expression suggests receptor levels or altered signaling pathways may reduce sensitivity to dsRNA. Funding provided by National Cancer Institute & Jimmy V Foundation.