Zhang H, Hoang T, Saeed B, Ng S C
Department 4MG, Aging and Degenerative Diseases Research, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Prostate. 1996 Aug;29(2):69-76. doi: 10.1002/(SICI)1097-0045(199608)29:2<69::AID-PROS1>3.0.CO;2-C.
We are interested in studying the possibility of modulating prostatic cell growth by manipulating apoptosis. Here we show that 1 microM staurosporine (STS) induces a human androgen-independent prostatic tumor cell line, DU145, to undergo dramatic changes in morphology and results in programmed cell death. Several genes involved in apoptosis were analyzed for expression in STS-treated and untreated DU145 cells. It was observed that these genes were differentially regulated. The expression level of bcl-2, bcl-xL, Ich-1L remains unchanged in treated and untreated cells. On the other hand, DAD1 and interleukin-1 beta-converting enzyme (ICE) were downregulated while bcl-xs and Ich-1s were upregulated. By blocking bcl-2 gene expression using antisense oligonucleotides, it was determined that the anti-bcl-2 oligonucleotides have no effect on the proliferation of DU145 or STS-treated DU145 cells. These results demonstrate that programmed cell death can be induced in an androgen-independent prostatic cancer cell line and BCL-2 was found not to play an important role in preventing STS-induced apoptosis in the DU145 cell line.
我们感兴趣于研究通过调控细胞凋亡来调节前列腺细胞生长的可能性。在此我们表明，1微摩尔的星形孢菌素（STS）可诱导一种人雄激素非依赖性前列腺肿瘤细胞系DU145发生形态学上的显著变化，并导致程序性细胞死亡。分析了几种参与细胞凋亡的基因在经STS处理和未处理的DU145细胞中的表达情况。观察到这些基因受到不同的调控。bcl-2、bcl-xL、Ich-1L在处理组和未处理组细胞中的表达水平保持不变。另一方面，DAD1和白细胞介素-1β转换酶（ICE）表达下调，而bcl-xs和Ich-1s表达上调。通过使用反义寡核苷酸阻断bcl-2基因表达，确定抗bcl-2寡核苷酸对DU145或经STS处理的DU145细胞的增殖没有影响。这些结果表明，在雄激素非依赖性前列腺癌细胞系中可诱导程序性细胞死亡，并且发现BCL-2在预防DU145细胞系中STS诱导的细胞凋亡方面不发挥重要作用。
