Linked Life Data

15004512

Source:http://linkedlifedata.com/resource/pubmed/id/15004512

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-3-8
pubmed:abstractText
Multiple myeloma (MM) remains fatal despite all available therapies. Initial treatment with conventional drugs such as, Dexamethasone (Dex) effectively induces MM cell death; however, prolonged drug exposures results in the development of chemoresistance. Our prior study demonstrated that 2-Methoxyestradiol (2ME2) induces apoptosis in multiple myeloma (MM) cells resistant to Dexamethasone (Dex). Here, we show the mechanism whereby 2ME2 overcomes Dex-resistance. The oligonucleotide array analysis demonstrates that Heat Shock Protein-27 (Hsp27) is upregulated in Dex-resistant, but not in Dex-sensitive MM cells. Proteomics analysis of Hsp27-immunocomplexes revealed the presence of actin in Dex-resistant, but not in Dex-sensitive cells. Biochemical interaction between Hsp27 and actin was examined by co-immunoprecipitation with anti-Hsp27 or actin Abs. Far western blot analysis using GST-Hsp27 fusion protein showed a direct association with actin both in vitro and in vivo. Importantly, 2ME2- or Bortezomib/Proteasome inhibitor (PS-341)-induced apoptosis in Dex-resistant MM cell lines and MM patient cells is associated with disruption of the Hsp27-actin complexes. Finally, blockade of Hsp27 by anti-sense strategy enhanced anti-MM activity of both 2ME2 and PS-341. These findings provide the clinical application of novel therapeutics targeting Hsp27 to improve patient outcome in MM.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1360-8185
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Kluwer Academic Publishers
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
149-55
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
2-Methoxyestardiol and bortezomib/proteasome-inhibitor overcome dexamethasone-resistance in multiple myeloma cells by modulating Heat Shock Protein-27.
pubmed:affiliation
The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't