Egawa S, Kadmon D, Miller G J, Scardino P T, Thompson T C
Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030.
Mol Carcinog. 1992;5(1):52-61. doi: 10.1002/mc.2940050110.
A clonal mouse prostate carcinoma was established by the introduction of the ras and myc oncogenes via the recombinant retrovirus Zipras/myc 9 using a mouse prostate reconstitution model system. A single-cell suspension derived from an early passage ras+myc-induced carcinoma was inoculated into the flanks of intact or castrated adult male C57BL/6 mice, and tumors were harvested 3 wk postinoculation for northern and Southern blotting. Tumor volume analysis showed that this carcinoma was not dependent on testicular androgens for growth. Southern blot analysis of virus-cell DNA junction fragments revealed that tumor cell populations recovered from both intact and castrated mice were progeny of the same virus-infected cell. Northern blotting showed that mRNA levels for the four growth-related genes transforming growth factor-beta 1 (TGF-beta 1), transforming growth factor-beta 3 (TGF-beta 3), tissue-type plasminogen activator (tPA), and c-myc were significantly elevated in clonal mouse prostate carcinomas grown in castrated hosts. In contrast, androgen receptor mRNA levels were significantly reduced under the same conditions. The response of TGF-beta 1, tPA, and c-myc mRNA levels in the carcinomas grown in castrated hosts was similar to that shown previously in normal rat ventral prostate. However, unlike normal rat ventral prostate after castration, increased numbers of apoptotic cells were not seen in the castrated group relative to the intact group at the time of analysis, indicating that the altered gene expression was not associated with cell death. In addition, testosterone-repressed prostate mRNA number 2 levels, shown previously to be elevated after castration in normal rat ventral prostate, were not increased in the androgen-deprived clonal mouse prostate carcinomas. Therefore, this early passage clonal ras+myc-induced prostate carcinoma demonstrates unique patterns of expression for a set of growth-related genes in an androgen-deprived environment.
通过使用小鼠前列腺重建模型系统，经重组逆转录病毒Zipras/myc 9导入ras和myc癌基因，建立了一种克隆性小鼠前列腺癌。将来自早期传代的ras+myc诱导癌的单细胞悬液接种到完整或去势成年雄性C57BL/6小鼠的侧腹，接种3周后收获肿瘤用于Northern和Southern印迹分析。肿瘤体积分析表明，这种癌的生长不依赖于睾丸雄激素。病毒-细胞DNA连接片段的Southern印迹分析显示，从完整和去势小鼠中回收的肿瘤细胞群体是同一病毒感染细胞的后代。Northern印迹显示，在去势宿主中生长的克隆性小鼠前列腺癌中，四种与生长相关的基因，即转化生长因子-β1（TGF-β1）、转化生长因子-β3（TGF-β3）、组织型纤溶酶原激活剂（tPA）和c-myc的mRNA水平显著升高。相反，在相同条件下雄激素受体mRNA水平显著降低。去势宿主中生长的癌中TGF-β1、tPA和c-myc mRNA水平的反应与先前在正常大鼠腹侧前列腺中观察到的相似。然而，与去势后的正常大鼠腹侧前列腺不同，在分析时去势组相对于完整组未见凋亡细胞数量增加，这表明基因表达的改变与细胞死亡无关。此外，先前显示在正常大鼠腹侧前列腺去势后升高的睾酮抑制前列腺mRNA 2水平，在雄激素剥夺的克隆性小鼠前列腺癌中并未升高。因此，这种早期传代的克隆性ras+myc诱导的前列腺癌在雄激素剥夺环境中表现出一组与生长相关基因的独特表达模式。
