Elsevier

Urology

Volume 72, Issue 3, September 2008, Pages 470-473
Urology

Rapid Communication
Decreased Bladder Cancer Growth in Parous Mice

https://doi.org/10.1016/j.urology.2008.04.028Get rights and content

Objectives

To investigate the association between parity and exophytic bladder cancer growth in the UPII-SV40T transgenic mouse model of bladder cancer.

Methods

The UPII-SV40T transgenic mice express the simian virus 40 large T antigen specifically in the urothelium (driven by uroplakin II promoter) and reliably develop bladder cancer. UPII-SV40T transgenic female mice were either never bred (nulliparous; n = 6) or placed in breeding pairs and allowed full-term pregnancies and lactation. Multiparous animals (n = 5) had between 2 and 4 litters. UPII-SV40T transgenic male mice were sham-operated (intact; n = 9) or castrated (n = 8) at 24 weeks of age. Noninvasive, contrast-enhanced, flat panel detector-based, cone beam computed tomographic imaging of animals at 32 weeks of age permitted quantification of bladder cancer volumes.

Results

Multiparous animals had significantly smaller bladder cancers than their nulliparous female (P < .001) and intact male (P = .007) counterparts but not different from castrated males. Bladder cancer volume in nulliparous females was significantly larger than castrated males (P < .001) but not different from intact males.

Conclusions

These results suggest that pregnancy, parity, lactation, or a combination of these may play a protective role in bladder cancer by inhibiting tumor growth. This could be an important model system for studying the effects of pregnancy/lactation hormones on bladder cancer, which could lead to identification of additional risk factors of bladder cancer.

Section snippets

Transgenic Mice

UPII-SV40T transgenic mice, which express SV40T antigen specifically in the urothelium and reliably develop noninvasive BC, were a gift from Drs. Tung-Tien Sun and Xue-Ru Wu of New York University.10 Animals were humanely handled in accordance to institutional and federal guidelines. Male UPII-SV40T transgenic mice were either sham-operated (n = 9) or castrated (n = 8) at 24 weeks of age as previously described.11 Sham operations included all physical manipulations of castration, except the

Results

We analyzed BC volume in mice at 32 weeks of age by noninvasive, contrast-enhanced CT scanning. Contrast dye in the bladder is visible as a positive image in a negative field. Filling defects in the bladder indicate the lumenal protrusion of exophytic BC (arrow, Fig. 1). The filling defects were confirmed as BC via histologic analysis after death: sham-operated males and nulliparous females had large urothelial carcinomas; castrated males had papillary BC; and in multiparous females, urothelial

Comment

As BC incidence in men outnumbers that of women, it would be remiss not to address the hormonal/sex differences involved in BC. Although the transgenic strategy used in the UPII-SV40T transgenic mice does not have sexual bias in BC incidence (all animals—male and female—had BC develop), intact male mice had larger BC volumes develop than did female mice. Castration and pregnancy dramatically alter the hormonal milieu, and castration and parity both appear to have an inhibitory role on the

Conclusions

The results of this study are the first to show that parity affects the growth of BC in rodents, lending itself to becoming a model for studying the effects of pregnancy, parity (age at first litter, number of litters), and nursing (length of time allowed). Future work is necessary to elucidate the role of pregnancy as a protective factor in BC. This could lead to the identification of risk factors, new treatments, or preventive agents for BC.

References (15)

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This study was supported by National Institute of Health grant DK 063126.

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