Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-1-27
pubmed:abstractText
The INI1 gene, which encodes a functionally uncharacterized protein component of the hSWI/SNF chromatin remodeling complex, is often mutated or deleted in malignant rhabdoid tumor (MRT). Two isoforms of INI1, that differ by the variable inclusion of nine amino acids, potentially are produced by differential RNA splicing. To determine the effect of the two INI1 isoforms on cell growth, INI1-devoid (MRT) and INI1-expressing cell lines were transfected separately with mammalian expression vectors or transduced with adenoviruses. Transfection of the short form of INI1 into either INI1-deficient or expressing cell lines resulted in complete suppression of cell growth in colony formation assays. The longer splice variant induced moderate to severe growth suppression of MRT cells, but had a far milder effect on non-MRT cells. Transduction of MRT cells with adenoviruses expressing either isoform of INI1 led to a dramatic change in morphology, growth suppression, and cell cycle arrest. Furthermore, senescence-associated proteins were up-regulated after transduction, while levels of proteins implicated in cell cycle progression were down-regulated. Adenoviral delivery of INI1 into a non-MRT cell line, however, had no demonstrable effect on any of these parameters. These results support the genetic evidence that INI1 is a tumor suppressor gene gone awry in MRT cells, and also suggest that delivery of the INI1 gene to MRT cells by adenoviruses may lead to a more effective treatment of this highly aggressive malignancy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9541
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
194
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
303-13
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12548550-Adenoviridae, pubmed-meshheading:12548550-Biological Markers, pubmed-meshheading:12548550-Breast Neoplasms, pubmed-meshheading:12548550-Cell Aging, pubmed-meshheading:12548550-Cell Cycle, pubmed-meshheading:12548550-Chromosomal Proteins, Non-Histone, pubmed-meshheading:12548550-DNA-Binding Proteins, pubmed-meshheading:12548550-Fluorescent Antibody Technique, pubmed-meshheading:12548550-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12548550-Genes, Tumor Suppressor, pubmed-meshheading:12548550-Genetic Vectors, pubmed-meshheading:12548550-HeLa Cells, pubmed-meshheading:12548550-Humans, pubmed-meshheading:12548550-Kidney Tubules, Proximal, pubmed-meshheading:12548550-Rhabdoid Tumor, pubmed-meshheading:12548550-Transcription Factors, pubmed-meshheading:12548550-Tumor Stem Cell Assay
pubmed:year
2003
pubmed:articleTitle
INI1 expression induces cell cycle arrest and markers of senescence in malignant rhabdoid tumor cells.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't