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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1994-4-7
pubmed:abstractText
Eight protein tyrosine kinase inhibitors with in vitro epidermal growth factor receptor kinase 50% inhibitory concentration values ranging from 0.043 to 22 microM were studied for their ability to inhibit the growth of the murine interleukin-3 (IL-3) dependent myeloid 32D cl3(G) cell line and, a subclone (LG7) transformed to IL-3 independent growth by retroviral transduction and expression of the chronic myelogenous leukemia-associated protein tyrosine kinase p210bcr/abl. Cell proliferation 50% inhibitory concentration values ranged from 4 to 250 microM, and one compound was not inhibitory at 500 microM. The dose-cell proliferation curves were remarkably similar for parental 32D cl3(G) cells + IL-3 and LG7 +/- IL-3, and reversion of LG7 cells to IL-3 dependence was not observed, suggesting that none of the compounds tested could selectively inhibit p210bcr/abl. However, 6 compounds induced the appearance of a 200-base pair nucleosomal DNA ladder characteristic of apoptosis at 24 h in parental 32D cl3(G) cells + IL-3, which mimicked the effects of IL-3 withdrawal alone, but not in similarly growth arrested LG7 cells that eventually developed a necrotic pattern of DNA fragmentation. These studies suggest that the expression of p210bcr/abl can suppress apoptotic signal transduction and that this may contribute to the development of the myeloid hyperplasia that occurs in chronic phase chronic myelogenous leukemia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
54
pubmed:geneSymbol
bcr-abl, neo
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1360-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
bcr/abl expression in 32D cl3(G) cells inhibits apoptosis induced by protein tyrosine kinase inhibitors.
pubmed:affiliation
Department of Medicine, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't