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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1994-4-7
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Mar
|
pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
1
|
pubmed:volume |
54
|
pubmed:geneSymbol |
bcr-abl,
neo
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
1360-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8118826-Animals,
pubmed-meshheading:8118826-Apoptosis,
pubmed-meshheading:8118826-Cell Death,
pubmed-meshheading:8118826-Cell Division,
pubmed-meshheading:8118826-Cell Line,
pubmed-meshheading:8118826-Fusion Proteins, bcr-abl,
pubmed-meshheading:8118826-Gene Transfer Techniques,
pubmed-meshheading:8118826-Hematopoietic System,
pubmed-meshheading:8118826-Interleukin-3,
pubmed-meshheading:8118826-Mice,
pubmed-meshheading:8118826-Protein-Tyrosine Kinases,
pubmed-meshheading:8118826-Signal Transduction
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pubmed:year |
1994
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pubmed:articleTitle |
bcr/abl expression in 32D cl3(G) cells inhibits apoptosis induced by protein tyrosine kinase inhibitors.
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pubmed:affiliation |
Department of Medicine, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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