Linked Life Data

19270519

Source:http://linkedlifedata.com/resource/pubmed/id/19270519

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-3-24
pubmed:abstractText
Tetraploid cells may constitute a metastable intermediate between normal euploidy and cancer-associated aneuploidy. Tetraploid cells are relatively more resistant against DNA damaging agents and are genetically unstable, due to their tendency towards multipolar, asymmetric division. Therefore, it is important to develop strategies for the selective removal of tetraploid cells. Here, we show that targeting the mitotic kinesin Eg5 (also known as kinesin spindle protein, KSP) by a small interfering RNA (siRNA) or by the pharmacological inhibitor dimethylenastron (DIMEN) kills tetraploid tumor cells more efficiently than their diploid precursors. Cell death occurs after an attempt of monoastral mitosis that, in diploid cells, is followed by a prolonged mitotic arrest and morphological reversion to the interphase, with a 4n DNA content. In contrast, DIMEN-treated tetraploid cells exhibit a shorter mitotic arrest, bipolar or multipolar karyokinesis, followed by apoptosis of the daughter cells, as assessed by fluorescence videomicroscopy of cells that express a histone 2B-GFP fusion construct to monitor their chromosomes. Cell death occurred with hallmarks of apoptosis, namely loss of the mitochondrial transmembrane potential and terminal chromatin compaction. In conclusion, tetraploid cells are particular vulnerable to undergo mitotic catastrophe after genetic or pharmacological inhibition of Eg5.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1030-5
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Preferential killing of tetraploid tumor cells by targeting the mitotic kinesin Eg5.
pubmed:affiliation
INSERM U848, Institut Gustave Roussy, and Université de Paris 11, Villejuif, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't