Chemoprevention of BBN-Induced Bladder Carcinogenesis by the Selective Estrogen Receptor Modulator Tamoxifen
Related Experiment Video
Updated: May 10, 2026
Magnetic Resonance Imaging Assessment of Carcinogen-induced Murine Bladder Tumors
Published on: March 29, 2019
Suraj Konnath George1, Veronica Tovar-Sepulveda, Steven S Shen
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
Abstract:
Bladder cancer is the fifth most frequent tumor in men and ninth in women in the United States. Due to a high likelihood of recurrence, effective chemoprevention is a significant unmet need. Estrogen receptors (ERs), primarily ERβ, are expressed in normal urothelium and urothelial carcinoma, and blocking ER function with selective ER modulators such as tamoxifen inhibits bladder cancer cell proliferation in vitro. Herein, the chemoprotective potential of tamoxifen was evaluated in female mice exposed to the bladder-specific carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Carcinogen treatment resulted in a 76% tumor incidence and increased mean bladder weights in comparison to controls. In contrast, mice receiving tamoxifen concurrent (8-20 weeks) or concurrent and subsequent (8-32 weeks) to BBN administration had no change in bladder weight and only 10% to 14% incidence of tumors. Non-muscle-invasive disease was present in animals treated with tamoxifen before (5-8 weeks) or after (20-32 weeks) BBN exposure, while incidence of muscle-invasive bladder carcinoma was reduced. ERβ was present in all mice and thus is a potential mediator of the tamoxifen chemoprotective effect. Surprisingly, ERα expression, which was detected in 74% of the mice exposed to BBN alone but not in any controlmice, was correlated with tumor incidence, indicating a possible role for this receptor in carcinogen-induced urothelial tumorigenesis. Thus, these data argue that both ERα and ERβ play a role in modulating carcinogen-induced bladder tumorigenesis. Administration of tamoxifen should be tested as a chemopreventive strategy for patients at high risk for bladder cancer recurrence.
Insights
Tamoxifen, a selective estrogen receptor modulator, shows promise in preventing bladder cancer recurrence. This study found tamoxifen significantly reduced tumor incidence and severity in mice exposed to a carcinogen.
Area of Science:
- Oncology
- Urology
- Endocrinology
Background:
- Bladder cancer is a frequent malignancy with a high recurrence rate, necessitating effective chemoprevention strategies.
- Estrogen receptors (ERs), particularly ERβ, are implicated in urothelial carcinoma, and their inhibition may offer a therapeutic avenue.
- Selective estrogen receptor modulators (SERMs) like tamoxifen have demonstrated in vitro efficacy in inhibiting bladder cancer cell proliferation.
Purpose of the Study:
- To evaluate the chemoprotective potential of tamoxifen against carcinogen-induced bladder tumorigenesis in a mouse model.
- To investigate the roles of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in bladder cancer development.
Main Methods:
- Female mice were exposed to the bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN).
- Tamoxifen was administered concurrently and/or subsequently to BBN exposure.
- Bladder weight, tumor incidence, and tumor invasiveness were assessed.
- Expression levels of ERα and ERβ were analyzed in relation to treatment and tumor development.
Main Results:
- BBN exposure led to a 76% tumor incidence and increased bladder weight.
- Concurrent or subsequent tamoxifen administration significantly reduced tumor incidence to 10-14% and prevented weight gain.
- Tamoxifen treatment resulted in non-muscle-invasive disease and reduced muscle-invasive carcinoma.
- ERβ was universally present, while ERα expression correlated with tumor incidence in BBN-exposed mice.
Conclusions:
- Tamoxifen demonstrates significant chemoprotective effects against carcinogen-induced bladder cancer in mice.
- Both ERα and ERβ appear to play roles in modulating bladder tumorigenesis.
- Tamoxifen warrants investigation as a chemopreventive strategy for patients at high risk of bladder cancer recurrence.
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