Linked Life Data

6120766

Source:http://linkedlifedata.com/resource/pubmed/id/6120766

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2 Pt 1
pubmed:dateCreated
1982-5-12
pubmed:abstractText
Several observations have suggested that microtubule depolymerization might act as a regulator of cell proliferation. To determine whether microtubule depolymerization is required for growth-factor-induced initiation of DNA synthesis, we treated serum-free cultures of mouse embryo cells with taxol to stabilize their microtubules and measured the initiation of DNA synthesis by thrombin and epidermal growth factor (EGF). Pretreatment of quiescent cultures of mouse embryo cells with 10 microgram/ml taxol inhibited up to 60% of the thrombin-stimulated and 47% of the EGF-stimulated DNA synthesis. This inhibition was dose-dependent for taxol concentrations from 0.3 to 20 microgram/ml. Control experiments showed that taxol did not simply affect uptake of nucleotides, glucose or amino acids, nor did it nonspecifically affect protein synthesis, cell morphology or cell viability. Taxol did not affect binding and internalization of 125I-thrombin or 125I-EGF indicating that the drug does not alter receptor number, affinity or distribution after growth factor binding. Taxol also did not affect the proteolytic activity of thrombin. Thus it appears that the inhibitory effects of taxol are mediated by a direct effect of taxol on microtubules. To determine at what point microtubule stabilization was interrupting the initiation signal, we added taxol at various times after addition of thrombin or EGF. Taxol addition during the first 8 hr after growth factor addition inhibited initiation, but after 8 hr had little if any effect. These results confirm that taxol was not nonspecifically affecting transport or metabolism required for DNA synthesis and indicate that thrombin and EGF may initiate cell proliferation through a gradual microtubule depolymerization or rearrangement that is necessary to commit cells to a replicative cycle.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0092-8674
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
341-50
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1981
pubmed:articleTitle
Microtubule stabilization by taxol inhibits initiation of DNA synthesis by thrombin and by epidermal growth factor.
pubmed:publicationType
Journal Article