Response to a lethal dose of heat shock by a transient up-regulation of clusterin expression followed by down-regulation and apoptosis in prostate and bladder cancer cells

Angela J. Wu, Irwin I. Park, Lei Zhaung, Chung Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

BACKGROUND. Clusterin is a ubiquitous, secretory glycoprotein with a wide array of functions. Recent studies have implicated that clusterin functioned as heat shock response proteins. The objective of the present study was to determine the fate of clusterin expression in cancer cells, which were subjected to a lethal dose of heat shock, in an attempt to shed light on mechanisms of action of clusterin. METHODS. A prostate cancer line, PC-3, and a bladder cancer line, TSU-Pr1, were selected owing to their aggressive growth behaviors. Apoptosis was assessed by enzymatic activities of terminal deoxynucleotidyl transferase as well as by activities of caspase-3. Cells were exposed to 45°C for a period of 60 min. RESULTS. Both cell lines underwent a transient up-regulation of clusterin expression followed by down-regulation and apoptosis. TSU-Pr1 cells produced higher levels of clusterin and displayed a greater resistance to apoptosis than did PC-3 cells. The addition of exogenous clusterin to the cultures of PC-3 cells protected apoptosis. Treatment of oligonucleotide antisense to clusterin to the cultures of TSU-Pr1 cells enhanced apoptosis mediated by heat shock. CONCLUSION. Clusterin offers a protection to PC-3 and TSU-Pr1 cells against heat shock and plays an important role in the cascade of events initiated by heat shock.

Original languageEnglish (US)
Pages (from-to)277-285
Number of pages9
JournalProstate
Volume53
Issue number4
DOIs
StatePublished - Dec 1 2002

Keywords

  • Apoptosis
  • Cancer cells
  • Clusterin expression
  • Heat shock

ASJC Scopus subject areas

  • Oncology
  • Urology

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