Molecular evaluation of metastatic prostatic cancer and the study on enhancement of their effects treating for non-tratment and refractory prostatic cancer.

1)前列腺癌血行微转移的分子生物学评价我们根据临床分期统计选择患者，这些患者预先保存了外周血PSA值、PSA mRNA等数据。本研究采用RT-PCR方法检测前列腺癌细胞系中雄激素受体（AR）和雌激素受体（ER）的表达，并对AR阴性前列腺癌细胞系中AR和ER的表达进行检测（PC 3、DU-145、TSUPr-1）和AR阳性细胞系（LNCap）暴露剂，如干扰素（INF）、5-氮杂胞苷、全反式视黄酸（ATRA），其具有潜在的细胞分化活性。（1）INF和ATRA对前列腺癌细胞株均无增殖抑制作用，而5-氮胞苷对这四种前列腺癌细胞株均有一定的增殖抑制作用。这一结果表明，这种诱导活性依赖于细胞周期或转录机制的启动子。(2)A从细胞周期的角度来看，这一系统与p16这一已知的抑癌基因有关。p16 mRNA在DU 145中表达较高，在LNCap中表达较低。此外，本身不表达p16蛋白的TSUPr-1和PC-3用5-氮胞苷诱导p16蛋白的表达，这意味着这四种前列腺细胞系的启动子区是去甲基化的。这一结果表明，细胞增殖抑制导致5-氮杂胞苷暴露于前列腺癌细胞系的高甲基化的可能性。下一步，我们计划评估与控制细胞周期相关的基因的表达，以证明端粒酶活性作为增殖和细胞分化的标志之一。

1)Molecular evaluation of hematogenous micro-metastasis from prostatic cancerStatistically we have selected patients according to their clinical stage, these patient had been preserved data such as PSA values, PSA mRNA from peripheral blood cells in advance. We are supposed to evaluate the relations between PSA value and the PSA expression using RT PCR.Now we are observing the clinical course these patients.2)Induction of expression in androgen receptor (AR) and estrogen receptor (ER) for four prostatic cancer cell lines.In our study, we evaluated an induction of AR and ER in AR-negative prostatic cell line (PC3, DU-145, TSUPr-1) and AR-positive cell line (LNCap) exposing agents such as interferon (INF), 5-azacytidine, all-trans retinoic acid (ATRA) which have an activity of potential cell differentiation.(1)There are no effects suppressing cell proliferation any cell lines using INF and ATRA.On the other hand, there are some effect suppressing cell proliferation using 5-azacytidine in these four prostatic cancer cell lines every concentrations. This results suggested that this induction activity is depend on cell cycle or promoter of transcription mechanism.(2)A cell cycle point of view, this system is related to p16 which is known to cancer suppressor gene. The p16 mRNA express high in DU145, low in LNCap. Furthermore TSUPr-1 and PC-3 which never express p16 protein in themselves induce the expression of p16 using 5-azacytidine.This means that the promoter region of these four prostatic cell line is demethylated. This result shows sate possibility that suppression of cell proliferation result in hypcmethylation exposing 5-azacytidine to prostatic cancer cell lines Next step we plan to evaluate the expression of genes which are related to controlling cell cycle, to demonstrate the telomerase activity as one of markers as proliferation and cell differentiation.