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Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-05-1417. This Article Full Text (PDF) All Versions of this Article: 2003-05-1417v1 102/9/3379    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chauhan, D. Articles by Anderson, K. C Search for Related Content PubMed PubMed Citation Articles by Chauhan, D. Articles by Anderson, K. C Social Bookmarking                   What's this? Submitted May 6, 2003 Accepted July 3, 2003 HSP27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers Dexamethasone resistance Dharminder Chauhan, Guilan Li, Teru Hideshima, Klaus Podar, Constantine Mitsiades, Nicholas Mitsiades, Laurence Catley, Yu Tzu Tai, Toshi Hayashi, Reshma Shringharpure, Renate Burger, Nikhil Munshi, Yasuyuki Ohtake, Satya Saxena, and Kenneth C Anderson* Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA Department of Oncology, The Jikei University School of Medicine, Tokyo, Japan Lovelace Respiratory Res. Institute, Alburquerque, NM, USA * Corresponding author; email: kenneth_anderson{at}dfci.harvard.edu. Smac, second mitochondria-derived activator of caspases promotes apoptosis via activation of caspases. Heat shock protein-27 (Hsp27) negatively regulates another mitochondrial protein, cytochrome-c during apoptosis; however, the role of Hsp27 in modulating Smac release is unknown. Here we show that Hsp27 is overexpressed in both Dexamethasone (Dex)-resistant multiple myeloma (MM) cell lines (MM.1R, U266, RPMI-8226) and primary patient cells. Blocking Hsp27 by an anti-sense (AS) strategy restores the apoptotic response to Dex in Dex-resistant MM cells via triggering the release of mitochondrial protein Smac, followed by activation of caspase-9 and -3. Moreover, AS-Hsp27 overcomes interleukin-6 (IL-6) mediated protection against Dex-induced apoptosis. These data demonstrate that Hsp27 inhibits the release of Smac, and thereby confers Dex-resistance in MM cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Cervantes-Gomez, R. Nimmanapalli, and V. Gandhi Transcription Inhibition of Heat Shock Proteins: A Strategy for Combination of 17-Allylamino-17-Demethoxygeldanamycin and Actinomycin D Cancer Res., May 1, 2009; 69(9): 3947 - 3954. [Abstract] [Full Text] [PDF] A. M. 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