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Apoptosis levels increase after castration in the CWR22 human prostate cancer xenograft
Author(s) -
Smitherman Andrew B.,
Gregory Christopher W.,
Mohler James L.
Publication year - 2003
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10271
Subject(s) - prostate cancer , castration , apoptosis , prostate , medicine , immunohistochemistry , androgen , androgen deprivation therapy , cancer , cancer research , oncology , biology , hormone , biochemistry
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. Prostate 57: 24–31, 2003. © 2003 Wiley‐Liss, Inc.