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.
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 degrees 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-Prl 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.


CONCLUSIONS
Clusterin offers a protection to PC-3 and TSU-Prl cells against heat shock and plays an important role in the cascade of events initiated by heat shock. Prostate 53: 277-285, 2002.
Wu
Angela J
AJ
Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Park
Irwin I
II
Zhaung
Lei
L
Lee
Chung
C
D017209:Apoptosis; D051152:Clusterin; D053938:DNA Fragmentation; D006023:Glycoproteins / Q000096:biosynthesis* / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D008297:Male; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*
C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones