Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2003-10-24
pubmed:databankReference
pubmed:abstractText
RNA interference (RNAi) is a powerful tool to induce loss-of-function phenotypes by inhibiting gene expression post-transcriptionally. Synthetic short interfering RNAs (siRNAs) as well as vector-based siRNA expression systems have been used successfully to silence gene expression in a variety of biological systems. We describe the development of an inducible siRNA expression system that is based on the tetracycline repressor and eukaryotic RNA polymerase III promoters (U6 and 7SK). For proof of concept we selectively inhibited expression of two catalytic subunits of the phosphatidylinositol 3-kinase (PI 3-kinase), p110alpha and p110beta, by using vector-derived short hairpin RNAs (shRNAs). Stable pools of human prostate cancer cells (PC-3) exhibiting reduced levels of both PI 3-kinase catalytic subunits due to the expression of corresponding shRNAs in an inducible fashion were established and analyzed for their invasive potential in vitro as well as in an orthotopic metastatic mouse model. This inducible system for RNAi allows an unbiased and comparable analysis of loss-of-function phenotypes by comparing selected isogenic cell populations on the induced and non-induced level. In addition, conditional RNAi allows the study of essential and multifunctional genes involved in complex biological processes by preventing inhibitory and compensatory effects caused by constitutive knockdown.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-10559867, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-10724036, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-10773442, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-11168386, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-11232238, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-11373684, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-11687500, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-11818553, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-11910072, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-11972060, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-11981553, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-11981564, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-11981565, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-11981566, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-12110901, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-12162696, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-12242156, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-12244328, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-12417750, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-12429690, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-12518064, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-12527776, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-12590264, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-12776180, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-1378502, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-1384042, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-8139567, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-9486653, http://linkedlifedata.com/resource/pubmed/commentcorrection/14576327-9759489
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1362-4962
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
e127
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:14576327-Animals, pubmed-meshheading:14576327-Catalytic Domain, pubmed-meshheading:14576327-Cell Line, Tumor, pubmed-meshheading:14576327-Disease Models, Animal, pubmed-meshheading:14576327-Gene Expression Regulation, Neoplastic, pubmed-meshheading:14576327-Humans, pubmed-meshheading:14576327-Male, pubmed-meshheading:14576327-Mice, pubmed-meshheading:14576327-Molecular Sequence Data, pubmed-meshheading:14576327-Nucleic Acid Conformation, pubmed-meshheading:14576327-Phosphatidylinositol 3-Kinases, pubmed-meshheading:14576327-Promoter Regions, Genetic, pubmed-meshheading:14576327-Prostatic Neoplasms, pubmed-meshheading:14576327-Protein Subunits, pubmed-meshheading:14576327-RNA, Small Interfering, pubmed-meshheading:14576327-RNA Interference, pubmed-meshheading:14576327-RNA Polymerase III, pubmed-meshheading:14576327-Tetracycline
pubmed:year
2003
pubmed:articleTitle
Inducible shRNA expression for application in a prostate cancer mouse model.
pubmed:affiliation
Atugen AG, Otto Warburg Haus (No. 80), Robert-Roessle-Strasse 10, 13125 Berlin, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't