Linked Life Data

8400801

Source:http://linkedlifedata.com/resource/pubmed/id/8400801

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1993-11-5
pubmed:abstractText
Expression of the bcl-2 gene becomes deregulated in many non-Hodgkin lymphomas as the result of t(14;18) chromosomal translocations. Because bcl-2 regulates the survival of cells, and because its over-expression is associated with cellular resistance to killing by chemotherapeutic drugs and gamma-irradiation, this gene and its mRNA and protein products represent ideal targets for designing novel therapeutic strategies for the treatment of cancer. Here we describe the effects of an 18-mer phosphodiester oligonucleotide that is complementary to the first 6 codons of the bcl-2 mRNA's open reading frame. When tested for inhibition of in vitro protein synthesis using RNAse-H-supplemented reticulocyte lysates and RNA prepared by in vitro transcription of a human bcl-2 cDNA, the bcl-2 antisense (AS) oligomer completely abolished Bcl-2 protein production at 10 microM, but had no effect on the in vitro translation of a chicken bcl-2 RNA that contained three mismatches relative to the oligomer binding site on the human bcl-2 RNA. A control 18-mer having the same base composition as the AS oligomer but with scrambled order (SC) was not inhibitory. Addition of AS and SC oligomers to cultures of a NIH-3T3 fibroblast cell line that had been stably infected with a recombinant retrovirus containing the same human bcl-2 cDNA used for in vitro transcription/translation experiments revealed concentration-dependent reductions in the relative levels of the 26-kD human Bcl-2 protein (as determined by immunoblotting) by the AS but not by the SC oligomer. Similar results were obtained when AS and SC oligomers were applied to a t(14;18)-containing lymphoma cell line SU-DHL-4 that was cultured in low-serum media. When used at 200 microM, the bcl-2 AS oligomer produced 84-95% reductions in Bcl-2 protein levels in SU-DHL-4 cells but had relatively little effect on the levels of other mitochondrial control proteins, suggesting that the inhibitory effects were specific. Treatment of SU-DHL-4 cells with AS oligomer lead to essentially complete loss of bcl-2 mRNA from cells within 1 day of addition to cultures, but presumably because of the long half-life of the Bcl-2 protein (approximately 14 h), commensurate reductions in Bcl-2 protein levels did not occur until 3 days.(ABSTRACT TRUNCATED AT 400 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1050-5261
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:geneSymbol
bcl-2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
157-69
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8400801-3T3 Cells, pubmed-meshheading:8400801-Animals, pubmed-meshheading:8400801-Base Sequence, pubmed-meshheading:8400801-Cell Line, pubmed-meshheading:8400801-Cell Survival, pubmed-meshheading:8400801-Humans, pubmed-meshheading:8400801-Immunoblotting, pubmed-meshheading:8400801-Lymphoma, Non-Hodgkin, pubmed-meshheading:8400801-Mice, pubmed-meshheading:8400801-Molecular Sequence Data, pubmed-meshheading:8400801-Oligonucleotides, Antisense, pubmed-meshheading:8400801-Polymerase Chain Reaction, pubmed-meshheading:8400801-Proto-Oncogene Proteins, pubmed-meshheading:8400801-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:8400801-RNA, Messenger, pubmed-meshheading:8400801-Transcription, Genetic, pubmed-meshheading:8400801-Translocation, Genetic, pubmed-meshheading:8400801-Tumor Cells, Cultured
pubmed:year
1993
pubmed:articleTitle
Investigations of antisense oligonucleotides targeted against bcl-2 RNAs.
pubmed:affiliation
La Jolla Cancer Research Foundation, Cancer Research Center, California.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.