Linked Life Data

21521802

Source:http://linkedlifedata.com/resource/pubmed/id/21521802

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2011-5-2
pubmed:abstractText
Rhabdoid tumors (RT) are aggressive pediatric malignancies with poor prognosis. INI1/hSNF5 is a component of the chromatin remodeling SWI/SNF complex and a tumor suppressor deleted in RT. Previous microarray studies indicated that reintroduction of INI1/hSNF5 into RT cells leads to repression of a high degree of mitotic genes including Aurora Kinase A (Aurora A, STK6). Here, we found that INI1/SNF5 represses Aurora A transcription in a cell-type-specific manner. INI1-mediated repression was observed in RT and normal cells but not in non-RT cell lines. Chromatin immunoprecipitation (ChIP) assay indicated that INI1/hSNF5 associates with Aurora A promoter in RT and normal cells but not in non-RT cells. Real-time PCR and immunohistochemical analyses of primary human and mouse RTs harboring mutations in INI1/hSNF5 gene indicated that Aurora A was overexpressed/derepressed in these tumor cells, confirming that INI1/hSNF5 represses Aurora A in vivo. Knockdown of Aurora A impaired cell growth, induced mitotic arrest and aberrant nuclear division leading to decreased survival, and increased cell death and caspase 3/7-mediated apoptosis in RT cells (but not in normal cells). These results indicated that Aurora A is a direct downstream target of INI1/hSNF5-mediated repression in RT cells and that loss of INI1/hSNF5 leads to aberrant overexpression of Aurora A in these tumors, which is required for their survival. We propose that a high degree of Aurora A expression may play a role in aggressive behavior of RTs and that targeting expression or activity of this gene is a novel therapeutic strategy for these tumors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3225-35
pubmed:meshHeading
pubmed-meshheading:21521802-Animals, pubmed-meshheading:21521802-Apoptosis, pubmed-meshheading:21521802-Caspase 3, pubmed-meshheading:21521802-Caspase 7, pubmed-meshheading:21521802-Cell Growth Processes, pubmed-meshheading:21521802-Cell Line, Tumor, pubmed-meshheading:21521802-Chromatin Assembly and Disassembly, pubmed-meshheading:21521802-Chromosomal Proteins, Non-Histone, pubmed-meshheading:21521802-DNA-Binding Proteins, pubmed-meshheading:21521802-Gene Knockdown Techniques, pubmed-meshheading:21521802-HeLa Cells, pubmed-meshheading:21521802-Humans, pubmed-meshheading:21521802-Jurkat Cells, pubmed-meshheading:21521802-Mice, pubmed-meshheading:21521802-Mitosis, pubmed-meshheading:21521802-Molecular Targeted Therapy, pubmed-meshheading:21521802-Promoter Regions, Genetic, pubmed-meshheading:21521802-Protein-Serine-Threonine Kinases, pubmed-meshheading:21521802-RNA, Small Interfering, pubmed-meshheading:21521802-Rhabdoid Tumor, pubmed-meshheading:21521802-Transcription Factors, pubmed-meshheading:21521802-Transfection, pubmed-meshheading:21521802-Transplantation, Heterologous
pubmed:year
2011
pubmed:articleTitle
Aurora A is a repressed effector target of the chromatin remodeling protein INI1/hSNF5 required for rhabdoid tumor cell survival.
pubmed:affiliation
Department of Genetics, Albert Einstein College of Medicine, New York University, New York, NY, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't