Linked Life Data

1703037

Source:http://linkedlifedata.com/resource/pubmed/id/1703037

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1991-2-27
pubmed:abstractText
The hypomethylating chemotherapeutic drug 5-aza-2'-deoxycytidine (5AzadC) has been shown to induce cell differentiation in some systems, while promoting neoplastic transformation in others. Using both in vitro and in vivo models, we have explored the relationship between oncogene expression and the susceptibility of cells to malignant transformation by 5AzadC. The study involved several nontumorigenic subclones of NIH3T3 fibroblasts, including cells transfected with deregulated c-myc, as well as phenotypic revertants expressing v-Ki-ras or long terminal repeat-activated c-Ha-ras. Transient 5AzadC treatment of the oncogene-bearing cell lines was associated with a rapid and efficient neoplastic transformation. In some cases, over 50% of the cell population exhibited loss of contact inhibition of growth within 1 week of treatment. The transformants were capable of forming s.c. tumors and experimental lung metastases in recipient nude mice. In contrast, 5AzadC failed to induce malignant properties in control 3T3 cultures transfected with the bacterial neor gene; rather, treatment of these cells was associated with differentiation into adipocytes and myotubes. The differential response to 5AzadC was also observed in vivo, in mice first inoculated s.c. with the premalignant cells and then treated with 5AzadC 24 h later. In agreement with the in vitro model, tumor development in mice correlated with the presence of cells with activated ras or myc oncogenes. Cytidine analogs that do not inhibit DNA methylation (i.e., 6-azacytidine and 1-beta-D-arabinofuranosyl cytosine) had no effect on cell phenotype. The results indicate that exposure of cells to 5AzadC can lead to tumor progression both in vitro and in vivo and suggest that preexisting alterations in oncogene expression may facilitate the evolution of cancerous growth induced by hypomethylating agents.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
324-30
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:1703037-Animals, pubmed-meshheading:1703037-Azacitidine, pubmed-meshheading:1703037-Blotting, Northern, pubmed-meshheading:1703037-Cell Differentiation, pubmed-meshheading:1703037-Cell Line, pubmed-meshheading:1703037-Cell Survival, pubmed-meshheading:1703037-Cell Transformation, Neoplastic, pubmed-meshheading:1703037-Cocarcinogenesis, pubmed-meshheading:1703037-DNA, pubmed-meshheading:1703037-Genes, ras, pubmed-meshheading:1703037-Matrix Metalloproteinase 3, pubmed-meshheading:1703037-Metalloendopeptidases, pubmed-meshheading:1703037-Methylation, pubmed-meshheading:1703037-Mice, pubmed-meshheading:1703037-Mice, Nude, pubmed-meshheading:1703037-Neoplasm Metastasis, pubmed-meshheading:1703037-Proto-Oncogene Proteins c-myc, pubmed-meshheading:1703037-Proto-Oncogenes, pubmed-meshheading:1703037-RNA, Messenger
pubmed:year
1991
pubmed:articleTitle
Increased sensitivity of nontumorigenic fibroblasts expressing ras or myc oncogenes to malignant transformation induced by 5-aza-2'-deoxycytidine.
pubmed:affiliation
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't