title: Induction of BAG2 protein during proteasome inhibitor-induced apoptosis in thyroid carcinoma cells.
abstract: OBJECTIVE
  Proteasome inhibitors exhibit cytotoxic against tumours of different histology. However, the mechanism of apoptosis induction by these compounds remains unclear and is likely to be a complex cascade of events. Bcl-2-associated athanogene (BAG) family proteins are characterized by their property of interaction with a variety of partners involved in modulating the proliferation/death balance, including heat shock proteins (HSP), Bcl-2, Raf-1. The role of BAG family proteins in proteasome inhibition has not been elucidated.
  
  
  METHODS
  Effects of proteasome inhibitors on BAG2 expression were evaluated using real-time reverse transcription-polymerase chain reaction (RT-PCR). BAG2 expression was knocked down by small interfering RNAs (siRNA). Cell death was evaluated using Annexin V/propidium iodide staining and subsequent FACS.
  
  
  RESULTS
  The proteasome inhibitors, MG132, PSI, lactacystin and epoxomicin, induced BAG2 at the transcriptional level. MG132-induced apoptosis was significantly suppressed by BAG2 knockdown using RNA interference.
  
  
  CONCLUSIONS
  Our results suggest that BAG2 is a novel molecule induced by proteasome inhibition, which exhibits a pro-apoptotic property in death of thyroid cancer cells induced by proteasome inhibition.
authors.affiliation: Department of Biochemistry & Molecular Biology, China Medical University, Shenyang, China.
authors.forename: H-Q
authors.initials: HQ
authors.lastname: Wang
authors.forename: H-Y
authors.initials: HY
authors.lastname: Zhang
authors.forename: F-J
authors.initials: FJ
authors.lastname: Hao
authors.forename: X
authors.initials: X
authors.lastname: Meng
authors.forename: Y
authors.initials: Y
authors.lastname: Guan
authors.forename: Z-X
authors.initials: ZX
authors.lastname: Du
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015536:Down-Regulation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D018832:Molecular Chaperones; D011480:Protease Inhibitors / Q000494:pharmacology*; D061988:Proteasome Inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C492980:BAG2 protein, human; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D012333:RNA, Messenger