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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3379-3386. Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-05-1417. This Article Full Text 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 Citation Map 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. Related Collections Neoplasia Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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, Toshiaki Hayashi, Reshma Shringarpure, Renate Burger, Nikhil Munshi, Yasuyuki Ohtake, Satya Saxena, and Kenneth C. Anderson From the Jerome Lipper Multiple Myeloma Center, Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA; Asahi Breweries Ltd, Tokyo, Japan; and Lovelace Respiratory Research Institute, Albuquerque, NM. 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 antisense (AS) strategy restores the apoptotic response to Dex in Dex-resistant MM cells by triggering the release of mitochondrial protein Smac, followed by activation of caspase-9 and caspase-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. 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