Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance |
| |
Authors: | Chauhan Dharminder Li Guilan Hideshima Teru Podar Klaus Mitsiades Constantine Mitsiades Nicholas Catley Laurence Tai Yu Tzu Hayashi Toshiaki Shringarpure Reshma Burger Renate Munshi Nikhil Ohtake Yasuyuki Saxena Satya Anderson Kenneth C |
| |
Institution: | Jerome Lipper Multiple Myeloma Center, Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
| 点击此处可从《Blood》浏览原始摘要信息 |
| 点击此处可从《Blood》下载免费的PDF全文 |
|