| pubmed-article:15388581 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15388581 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:15388581 | lifeskim:mentions | umls-concept:C0007634 | lld:lifeskim |
| pubmed-article:15388581 | lifeskim:mentions | umls-concept:C0035820 | lld:lifeskim |
| pubmed-article:15388581 | lifeskim:mentions | umls-concept:C0085669 | lld:lifeskim |
| pubmed-article:15388581 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
| pubmed-article:15388581 | lifeskim:mentions | umls-concept:C0243043 | lld:lifeskim |
| pubmed-article:15388581 | lifeskim:mentions | umls-concept:C0683598 | lld:lifeskim |
| pubmed-article:15388581 | lifeskim:mentions | umls-concept:C0598002 | lld:lifeskim |
| pubmed-article:15388581 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:15388581 | pubmed:dateCreated | 2005-1-20 | lld:pubmed |
| pubmed-article:15388581 | pubmed:abstractText | Bcr-Abl-expressing primary or cultured leukemia cells display high levels of the antiapoptotic heat shock protein (hsp) 70 and are resistant to cytarabine (Ara-C), etoposide, or Apo-2L/TRAIL (TNF-related apoptosis-inducing ligand)-induced apoptosis. Conversely, a stable expression of the cDNA of hsp70 in the reverse orientation attenuated not only hsp70 but also signal transducers and activators of transcription 5 (STAT5) and Bcl-x(L) levels. This increased apoptosis induced by cytarabine, etoposide, or Apo-2L/TRAIL. Ectopic expression of hsp70 in HL-60 cells (HL-60/hsp70) inhibited Ara-C and etoposide-induced Bax conformation change and translocation to the mitochondria; attenuated the accumulation of cytochrome c, Smac, and Omi/HtrA2 in the cytosol; and inhibited the processing and activity of caspase-9 and caspase-3. Hsp70 was bound to death receptors 4 and 5 (DR4 and DR5) and inhibited Apo-2L/TRAIL-induced assembly and activity of the death-inducing signaling complex (DISC). HL-60/hsp70 cells exhibited increased levels and DNA binding activity of STAT5, which was associated with high levels of Pim-2 and Bcl-x(L) and resistance to apoptosis. Expression of the dominant negative (DN) STAT5 resensitized HL-60/hsp70 cells to cytarabine, etoposide, and Apo-2L/TRAIL-induced apoptosis. Collectively, these findings suggest that hsp70 inhibits apoptosis upstream and downstream of the mitochondria and is a promising therapeutic target for reversing drug-resistance in chronic myeloid leukemia-blast crisis and acute myeloid leukemia cells. | lld:pubmed |
| pubmed-article:15388581 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:15388581 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15388581 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:15388581 | pubmed:issn | 0006-4971 | lld:pubmed |
| pubmed-article:15388581 | pubmed:author | pubmed-author:DOWD CDC | lld:pubmed |
| pubmed-article:15388581 | pubmed:author | pubmed-author:LiL YLY | lld:pubmed |
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| pubmed-article:15388581 | pubmed:volume | 105 | lld:pubmed |
| pubmed-article:15388581 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15388581 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15388581 | pubmed:pagination | 1246-55 | lld:pubmed |
| pubmed-article:15388581 | pubmed:dateRevised | 2007-11-15 | lld:pubmed |
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| pubmed-article:15388581 | pubmed:year | 2005 | lld:pubmed |
| pubmed-article:15388581 | pubmed:articleTitle | Mechanistic role of heat shock protein 70 in Bcr-Abl-mediated resistance to apoptosis in human acute leukemia cells. | lld:pubmed |
| pubmed-article:15388581 | pubmed:affiliation | Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA. | lld:pubmed |
| pubmed-article:15388581 | pubmed:publicationType | Journal Article | lld:pubmed |
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