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Updated: Jul 5, 2026
Murine Prostate Micro-dissection and Surgical Castration
Published on: May 11, 2016
Divergent effects of castration on prostate cancer in TRAMP mice: possible implications for therapy
Yao Tang1, Linbo Wang, Olga Goloubeva
1Department of Medicine, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Purpose:
Divergent responses to androgen deprivation have been found in patients and in animal models of prostate cancer. The molecular basis for these different outcomes is unknown. Our aim was to identify the molecular responses of prostate cancer with divergent outcomes to androgen deprivation in TRAMP mice.
Experimental Design:
Castrated and noncastrated B6xFVB TRAMP mice were evaluated for survival, tumor development, pathology, and expressions of specific proteins at different time points.
Results:
TRAMP mice responded differentially to androgen deprivation. In the majority, primary tumors regressed after castration (positive response), whereas in others the tumors grew even more aggressively than in the noncastrated mice (negative response). Mice with regressed tumors had the highest survival rates. Androgen receptor was elevated in all tumors from castrated mice despite significant differences in tumor sizes. In positively responding tumors, expressions of Bcl-2 and Grp78 were greatly increased by 10 weeks after castration, whereas expressions of Bax, Bcl-xl, SV40 T antigen, and c-myc were lower. These tumors also showed a reduction in proliferating cells compared with noncastrates and negatively responding tumors. Most of these changes disappeared 20 weeks after castration, by which time there was an increase in the size of primary tumors as well as in distant metastasis.
Conclusions:
In TRAMP prostate cancer that responded positively to castration, different expression patterns of proteins involved in cellular apoptosis, stress, and proliferation occur approximately 10 weeks after castration. This may be an optimal time for targeting Bcl-2, and perhaps Grp78, to enhance the antitumor effects of androgen deprivation.
Insights
Prostate cancer in TRAMP mice shows varied responses to androgen deprivation. Targeting Bcl-2 and Grp78 proteins around 10 weeks post-castration may enhance treatment effects in positively responding tumors.
Area of Science:
- Oncology
- Molecular Biology
- Animal Models
Background:
- Prostate cancer exhibits diverse responses to androgen deprivation therapy (ADT).
- The molecular mechanisms underlying these divergent outcomes remain largely unknown.
- Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model offers a platform to study prostate cancer progression and ADT response.
Purpose of the Study:
- To investigate the molecular profiles of prostate cancer in TRAMP mice exhibiting differential responses to androgen deprivation.
- To identify key protein expression changes associated with tumor regression or progression following castration.
Main Methods:
- Castration and non-castration of B6xFVB TRAMP mice.
- Evaluation of survival rates, tumor development, pathology, and protein expression (Androgen Receptor, Bcl-2, Grp78, Bax, Bcl-xl, SV40 T antigen, c-myc) at different time points post-castration.
- Assessment of cellular proliferation markers.
Main Results:
- TRAMP mice displayed divergent responses to castration: tumor regression (positive responders) or aggressive growth (negative responders).
- Positively responding tumors showed increased Bcl-2 and Grp78, and decreased Bax, Bcl-xl, SV40 T antigen, and c-myc expressions around 10 weeks post-castration, with reduced proliferation.
- These molecular changes and tumor regression were transient, with tumor regrowth and metastasis observed by 20 weeks post-castration.
Conclusions:
- Distinct protein expression patterns related to apoptosis, stress, and proliferation emerge in TRAMP prostate cancer approximately 10 weeks after castration in positively responding tumors.
- Targeting Bcl-2 and Grp78 at this 10-week post-castration window may represent an optimal strategy to potentiate the anti-tumor effects of androgen deprivation.
- The transient nature of these beneficial molecular changes highlights the need for sustained therapeutic strategies.
