Apoptosis levels increase after castration in the CWR22 human prostate cancer xenograft.
BACKGROUND
The role of apoptosis in the regression of human prostate cancer after androgen deprivation therapy remains controversial. Detection of caspase-3, an ubiquitous effector of apoptosis, is a highly specific technique for in vivo evaluation of apoptosis.


METHODS
Apoptotic rates were evaluated in the androgen-dependent CWR22 human prostate cancer xenograft in tumors that represented time points throughout the progression from androgen-stimulated to recurrent prostate cancer. Caspase-3 levels in formalin-fixed, paraffin-embedded specimens were quantified using immunohistochemical detection and video image analysis. Western blot analysis was used to confirm the results of immunodetection.


RESULTS
Expression of caspase-3 reached a maximum on day 2 after castration, decreased on day 6, and remained low until tumor recurrence. The percentage of tumor area expressing caspase-3 increased from 2.51 +/- 0.44% in tumors from intact mice to 20.84 +/- 1.75% on day 2 after castration. Among immunopositive cells, the intensity of caspase-3 expression measured using the mean optical density (MOD) increased 45% (0.3762 +/- 0.003 to 0.5461 +/- 0.001) on day 2 after castration compared to levels detected in tumors from intact mice.


CONCLUSIONS
Apoptosis contributes to tumor regression after castration in the CWR22 human prostate cancer xenograft model.
Smitherman
Andrew B
AB
University of North Carolina Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Gregory
Christopher W
CW
Mohler
James L
JL
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018715:Microscopy, Video; D009368:Neoplasm Transplantation; D009919:Orchiectomy; D016612:Paraffin Embedding; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D014183:Transplantation, Heterologous
C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases