Clusterin is not essential for androgen-regulated involution and regeneration of the normal mouse prostate.
BACKGROUND
Inhibition of clusterin expression has been shown to enhance the sensitivity of prostate cancer cells to chemo and hormone therapy. Clusterin antisense oligonucleotides (ASOs) are currently in phase II human clinical trials for treatment of hormone refractory prostate cancer. However, the role of clusterin in androgen-regulated involution and regeneration of the normal prostate gland has not been established.


METHODS
Prostate involution and regeneration was examined in clusterin-deficient mice undergoing up to three cycles of androgen withdrawal and restoration.


RESULTS
Surprisingly, clusterin deficiency did not affect the apoptotic index, and the temporal biochemical and morphological changes associated with involution and regeneration of the normal adult prostate following multiple rounds of androgen withdrawal and replacement.


CONCLUSIONS
Clusterin is not critical for normal prostate development or androgen-regulated involution and regrowth of the mouse prostate gland, suggesting that clusterin may have distinct functions in malignant versus normal prostatic epithelial cells.
Fink
Dieter
D
The Prostate Centre at VGH, University of British Columbia, Vancouver, British Columbia, Canada.
Fazli
Ladan
L
Aronow
Bruce
B
Gleave
Martin E
ME
Ong
Christopher J
CJ
D000728:Androgens / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051152:Clusterin / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009919:Orchiectomy; D011467:Prostate / Q000166:cytology / Q000254:growth & development* / Q000502:physiology; D012038:Regeneration / Q000502:physiology*
D000728:Androgens; D051152:Clusterin