|
|
Potential triple helix-mediated inhibition of
IGF-I gene expression significantly reduces tumorigenicity of glioblastoma in an
animal model
Shevelev A, Burfeind P, Schulze E, Rininsland F, Johnson TR, Trojan J,
Chernicky CL, Helene C, Ilan J, Ilan J
Department of Pathology, Case Western Reserve University, School
of Medicine, Cleveland, OH 44106-4943, USA
Oligonucleotide-directed triple helix formation is a powerful approach to block
transcription of specific genes.
Although the oligonucleotide triplex approach is efficient for inhibiting gene
expression in cultured cells, suppression is transient.
We developed an approach which inhibits insulin-like growth factor-I (IGF-I)
expression following stable transfection of C6 rat glioblastoma cells with a
plasmid from which an RNA is transcribed that codes for the third strand of a
potential triple helix.
We tested the ability of this expression vector to inhibit IGF-I gene expression
in vitro as well as tumorigenesis in an animal.
A dramatic reduction of IGF-I RNA and protein levels in cultured cells occurred
following transfection of rat C6 cells with a eukaryotic expression plasmid
encoding the oligopurine variant of the triple helix but not the oligopyrimidine
or a control sequence.
The cells transfected with the oligopurine variant displayed morphological
changes, upregulation of major histocompatibility complex I, and increased
expression of protease nexin I.
Dramatic inhibition of tumor growth occurred in nude mice following injection of
transfected C6 cells.
To our knowledge, this is the first example of tumor growth inhibition in an
animal model employing a triple helix approach.
PMID: 9080119 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9080119&dopt=Abstract
|
