White-Gilbertson Shai, Davis Megan, Voelkel-Johnson Christina, Kasman Laura M
Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Ave., MSC 504, Charleston, SC 29425, USA.
Bladder (San Franc). 2016;3(1). doi: 10.14440/bladder.2016.73. Epub 2016 Feb 26.
The MB49 syngeneic, murine model of bladder cancer has been widely used for more than 35 years. In humans, bladder cancer is one third as prevalent in women as in men, with a trend toward lower prevalence in parous compared to nulliparous women. Our objective was to determine if the MB49 bladder cancer model reproduces the sex differences observed in humans, and to determine its sensitivity to testosterone and the pregnancy hormone, human chorionic gonadotropin (hCG).
Male and female C57BL/6 mice were implanted with MB49 murine bladder cancer cells, and observed for tumor growth. MB49 dose responses to hCG and dihydrotestosterone were determined .
MB49 tumor growth was significantly greater in male mice than female mice. Pregnancy did not affect MB49 tumor growth in female mice. MB49 cells did not proliferate in response to hCG and the functional receptor for gonadotropins was absent. Dihydrotestosterone strongly stimulated growth of MB49 cells .
The MB49 murine model of bladder cancer reproduced some aspects of the sex differences observed in humans. Our results suggest that testosterone may stimulate MB49 cell proliferation, which may explain the more rapid MB49 tumor growth observed in male mice.
MB49同基因小鼠膀胱癌模型已被广泛应用超过35年。在人类中,膀胱癌的患病率女性仅为男性的三分之一,且经产妇的患病率有低于未生育女性的趋势。我们的目的是确定MB49膀胱癌模型是否能再现人类中观察到的性别差异,并确定其对睾酮和妊娠激素人绒毛膜促性腺激素(hCG)的敏感性。
将MB49小鼠膀胱癌细胞植入雄性和雌性C57BL/6小鼠体内,观察肿瘤生长情况。测定MB49对hCG和二氢睾酮的剂量反应。
雄性小鼠的MB49肿瘤生长明显大于雌性小鼠。妊娠对雌性小鼠的MB49肿瘤生长没有影响。MB49细胞不会因hCG而增殖,且不存在促性腺激素的功能性受体。二氢睾酮强烈刺激MB49细胞的生长。
MB49小鼠膀胱癌模型再现了人类中观察到的性别差异的某些方面。我们的结果表明,睾酮可能刺激MB49细胞增殖,这可能解释了在雄性小鼠中观察到的MB49肿瘤生长更快的现象。