Linked Life Data

10935642

Source:http://linkedlifedata.com/resource/pubmed/id/10935642

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6794
pubmed:dateCreated
2000-8-17
pubmed:databankReference
pubmed:abstractText
Chemicals that target microtubules induce mitotic stress by affecting several processes that occur during mitosis. These processes include separation of the centrosomes in prophase, alignment of the chromosomes on the spindle in metaphase and sister-chromatid separation in anaphase. Many human cancers are sensitive to mitotic stress. This sensitivity is being exploited for therapy and implies checkpoint defects. The known mitotic checkpoint genes, which prevent entry into anaphase when the chromosomes are not properly aligned on the mitotic spindle, are, however, rarely inactivated in human cancer. Here we describe the chfr gene, which is inactivated owing to lack of expression or by mutation in four out of eight human cancer cell lines examined. Normal primary cells and tumour cell lines that express wild-type chfr exhibited delayed entry into metaphase when centrosome separation was inhibited by mitotic stress. In contrast, the tumour cell lines that had lost chfr function entered metaphase without delay. Ectopic expression of wild-type chfr restored the cell cycle delay and increased the ability of the cells to survive mitotic stress. Thus, chfr defines a checkpoint that delays entry into metaphase in response to mitotic stress.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0028-0836
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
406
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
430-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Chfr defines a mitotic stress checkpoint that delays entry into metaphase.
pubmed:affiliation
The Wistar Institute, Philadelphia, Pennsylvania 19104-4268, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.