title: Heat-shock proteins inhibit induction of prostate cancer cell apoptosis.
abstract: BACKGROUND
  Resistance to apoptosis remains a significant problem in the treatment of prostate cancer. Heat-shock proteins (HSP) have been correlated with tumor progression. The role of HSP in prostate cancer resistance to apoptosis is unknown.
  
  
  METHODS
  PC-3 and LNCaP prostate cancer cells were heat-shocked and then treated with or without diethyl-maleate, etoposide, cycloheximide, or 3 Gray irradiation. Percent apoptosis was assessed by propidium iodide DNA incorporation. Protein was also extracted for analysis by SDS-PAGE Western blotting.
  
  
  RESULTS
  Western blotting confirmed an increase in HSP 27 and 72. These cells were resistant to both chemical- and radiation-induced apoptosis. Cycloheximide and specific oligonucleotides to HSP 72 blocked the increased expression of HSP 72 and the resistance to apoptosis. Mcl-1, Bcl-2, Bcl-X(L), and glutathione-S-transferase (GST) expression were increased in a time-dependent manner after heat shock.
  
  
  CONCLUSIONS
  This study demonstrates that HSP expression, specifically HSP 72, inhibits apoptosis in prostate tumor cell lines, which may be mediated by the production of survival factors.
authors.affiliation: Department of Surgery, Mater Misericordiae Hospital, Conway Institute of Biomedicine and Biomolecular Research, University College Dublin, Ireland.
authors.forename: N B
authors.initials: NB
authors.lastname: Gibbons
authors.forename: R W
authors.initials: RW
authors.lastname: Watson
authors.forename: R N
authors.initials: RN
authors.lastname: Coffey
authors.forename: H P
authors.initials: HP
authors.lastname: Brady
authors.forename: J M
authors.initials: JM
authors.lastname: Fitzpatrick
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D015153:Blotting, Western; D003513:Cycloheximide / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005978:Glutathione / Q000096:biosynthesis; D005982:Glutathione Transferase / Q000096:biosynthesis; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008297:Male; D008298:Maleates / Q000494:pharmacology; D018832:Molecular Chaperones; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011836:Radiation Tolerance / Q000502:physiology; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494811:BCL2L1 protein, human; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D008298:Maleates; D018832:Molecular Chaperones; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D005047:Etoposide; D003513:Cycloheximide; D005982:Glutathione Transferase; C014476:diethyl maleate; D005978:Glutathione