Regulation of rat DOC-2 gene during castration-induced rat ventral prostate degeneration and its growth inhibitory function in human prostatic carcinoma cells.
Regulation of rat DOC-2 gene during castration-induced rat ventral prostate degeneration and its growth inhibitory function in human prostatic carcinoma cells.
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DOI：
10.1210/endo.139.8.6159
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发表时间：
1998-08
期刊：
影响因子：
4.8
通讯作者：
Ching-Ping Tseng;B. Ely;Yingming Li;R. Pong;J. Hsieh
中科院分区：
文献类型：
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作者：
Ching-Ping Tseng;B. Ely;Yingming Li;R. Pong;J. Hsieh
雄激素是一种有丝分裂原，也是前列腺上皮的形态形成原。然而，这些不同的雄激素作用的详细机制尚未被描述。因此，我们采用差异显示PCR来揭示可能参与这些过程的任何潜在基因。在这项研究中，我们报道了从大鼠腹侧前列腺（VP）中分离和鉴定了C9互补DNA的两种选择性剪接形式（p82和p59），即人类卵巢癌2缺失（DOC-2）基因和小鼠p96磷酸化蛋白的大鼠同源物。我们发现C9在去势大鼠VP中表达上调，提示C9可能在前列腺退化过程中直接或间接受到雄激素受体的调节。在精囊和前列腺背外侧也观察到类似的调节模式，但在凝血腺或其他雄激素非依赖性器官中没有。免疫组化分析显示，长时间去势后大鼠VP基底上皮和周围基质细胞中检测到C9。核糖核酸酶保护实验和Western blot分析显示p59是大鼠VP中主要的C9亚型。为了揭示C9在细胞生长中的功能，我们将p59的互补DNA转染到C4-2细胞中，C4-2是LNCaP前列腺癌细胞系的衍生物。在我们的实验条件下，p59稳定的转染物在G1期表现出较慢的生长速度和细胞分数的增加。这些数据表明C9-p59对前列腺上皮细胞具有生长抑制活性。综上所述，我们的研究结果表明，C9在前列腺退行性变过程中上调，可能在前列腺上皮的增殖和分化中发挥积极作用。
Androgen is a mitogen as well as a morphogen for prostatic epithelium. However, the detailed mechanisms of these distinct androgenic actions have not yet been delineated. Therefore, we employed differential display PCR to unveil any potential genes that may be involved in these processes. In this study, we report the isolation and characterization of two alternative splicing forms (p82 and p59) of C9 complementary DNA, the rat homolog of the human deletion of ovarian carcinoma 2 (DOC-2) gene and mouse p96 phosphoprotein, from rat ventral prostate (VP). We found that C9 was up-regulated in rat VP after castration, suggesting that C9 may be regulated by androgen receptor directly or indirectly during prostate degeneration. A similar regulatory pattern was also observed in both the seminal vesicle and dorsolateral prostate, but not in the coagulating gland or other androgen-independent organs. Immunohistochemical analysis of rat VP demonstrated that C9 is detected in the basal epithelia and surrounding stromal cells after prolonged castration. Ribonuclease protection assay and Western blot analysis revealed that p59 is the predominant C9 isoform in rat VP. To unveil the function of C9 in cell growth, we transfected p59 complementary DNA into the C4-2 cells, a derivative of the LNCaP prostatic carcinoma cell line. The p59 stable transfectants exhibited a slower growth rate and an increase in the cell fraction in the G1 phase under our experimental conditions. These data indicate that C9-p59 has growth inhibitory activity for prostatic epithelial cells. Taken together, our results suggest that C9 is up-regulated during prostate degeneration process and may play an active role in the proliferation and differentiation of prostatic epithelium.