Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-6-5
pubmed:abstractText
Tumor necrosis factor alpha (TNFalpha) potently inhibits the in vitro growth of highly purified human d-6 erythroid colony forming cells (ECFC). Unlike the inhibitory effect of TNFalpha on other cells, including more immature ECFC, this antiproliferative effect of TNFalpha is not related to apoptosis because the d-6 cell descendants were morphologically normal, without apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling assay and without caspase activation by Western blots after TNFalpha treatment. TNFalpha did not appear to affect the cell cycle distribution, but the cell cycle duration was significantly longer in TNFalpha-treated cells. DNA synthesis was also significantly reduced by TNFalpha. Studies of various proteins that regulate the cell cycle showed that cyclin-dependent kinase 6 (CDK6) protein and mRNA levels were concomitantly decreased in the presence of TNFalpha, suggesting that inhibition of cell growth was related to reduced CDK6. To evaluate this, the CDK6 gene was transferred into ECFC using green fluorescence protein-retrovirus-mediated gene transfer. The results showed that the level of cell growth produced by TNFalpha was increased by 30% when the cells were transfected with CDK6. Therefore, the modification of cell cycle progression in the presence of TNFalpha through a reduction of CDK6 is an important mechanism in the TNFalpha inhibition of human ECFC expansion.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0007-1048
pubmed:author
pubmed:issnType
Print
pubmed:volume
121
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
919-27
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Reduction of cell cycle progression in human erythroid progenitor cells treated with tumour necrosis factor alpha occurs with reduced CDK6 and is partially reversed by CDK6 transduction.
pubmed:affiliation
Department of Medicine, Department of Veterans Affairs Medical Center and Vanderbilt University, 2220 Pierce Avenue, Nashville, TN 37232-6307, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.