Source:http://linkedlifedata.com/resource/pubmed/id/10910051
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
13
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| pubmed:dateCreated |
2000-8-17
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| pubmed:abstractText |
Lack of selectivity in the killing of tumor and normal cells is a major obstacle in cancer therapy. By inhibiting normal but not autonomous cell growth, we exploited the differences in cell cycle regulation to achieve a selective protection of nonautonomous cells against paclitaxel and other microtubule-active drugs. Tubulin polymerization, a primary effect of paclitaxel, can be dissociated from Bcl-2 phosphorylation and cytotoxicity in HL-60 cells. Growth arrest prevented paclitaxel-induced Bcl-2 phosphorylation and apoptosis without affecting paclitaxel-induced tubulin polymerization. We abrogated the effects of paclitaxel on MCF-10A immortalized breast cells, while preserving its effects on MCF-7 cancer cells. Unlike MCF-7 cells, MCF-10A cells were arrested by epidermal growth factor withdrawal, precluding paclitaxel-induced Bcl-2 phosphorylation. Furthermore, the inhibition of the epidermal growth factor receptor kinase with low doses of AG1478 arrested growth of MCF-10A but not MCF-7 cells. Pretreatment with AG1478 did not affect paclitaxel-induced Bcl-2/Raf-1 phosphorylation in MCF-7 but abrogated such phosphorylation in MCF-10A. Exploitation of growth factor dependency may allow the protection of normal cells from microtubule-active drugs.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Paclitaxel,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Tubulin,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins,
http://linkedlifedata.com/resource/pubmed/chemical/tyrphostin AG 1478
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0008-5472
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
60
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3425-8
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| pubmed:dateRevised |
2004-11-17
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| pubmed:meshHeading |
pubmed-meshheading:10910051-Apoptosis,
pubmed-meshheading:10910051-Breast Neoplasms,
pubmed-meshheading:10910051-Cell Cycle,
pubmed-meshheading:10910051-Cell Division,
pubmed-meshheading:10910051-Cell Survival,
pubmed-meshheading:10910051-Enzyme Inhibitors,
pubmed-meshheading:10910051-Epidermal Growth Factor,
pubmed-meshheading:10910051-Female,
pubmed-meshheading:10910051-HL-60 Cells,
pubmed-meshheading:10910051-Humans,
pubmed-meshheading:10910051-Microtubules,
pubmed-meshheading:10910051-Mitosis,
pubmed-meshheading:10910051-Paclitaxel,
pubmed-meshheading:10910051-Phosphorylation,
pubmed-meshheading:10910051-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:10910051-Tetradecanoylphorbol Acetate,
pubmed-meshheading:10910051-Tubulin,
pubmed-meshheading:10910051-Tumor Cells, Cultured,
pubmed-meshheading:10910051-Tyrphostins
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| pubmed:year |
2000
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| pubmed:articleTitle |
Loss of cell cycle control allows selective microtubule-active drug-induced Bcl-2 phosphorylation and cytotoxicity in autonomous cancer cells.
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| pubmed:affiliation |
Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. mikhailb@box-m.nih.gov
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| pubmed:publicationType |
Journal Article
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