GENETIC ALTERATIONS OF PROSTATIC CANCER RELATING TO BONE METASTASIS AND PHENOTYPIC CHANGES.

首先，我们在我所做了前列腺癌的临床研究，并报告了结果。由于低期前列腺癌病例较少，我们不能彻底检测切除标本中c-myc、c-fos癌基因的表达或bcl2基因突变情况。AT6.3是一种高转移性的大鼠前列腺癌细胞系。我们报道了血管生成抑制剂TNP-470对AT6.3细胞肺转移的抑制作用。我们还发现人前列腺癌LNCaP、DU145和PC3细胞株具有抑制成骨细胞分化的活性。净化这项活动的工程目前正在进行中。由于我们无法从许多前列腺癌病例中获得材料，我们检查了我们研究所经常发现的其他泌尿系统肿瘤如肾细胞癌和睾丸肿瘤的相同类型的基因改变。基因组印迹是一种新的遗传调控实体，其中某些基因如胰岛素样生长因子II(IGF2)和H19基因只在单侧等位基因中表达。我们发现IGF2和H19基因在睾丸癌中以单侧等位基因的形式表达。这种基因改变目前正在前列腺癌的研究中。细胞凋亡是细胞死亡的一个新概念，在许多细胞中通常是通过Fas-Fas配体途径诱导的。在Fas途径的刺激下，前列腺癌细胞未出现典型的凋亡现象。反之，肾癌细胞表达Fas抗原，并表现出典型的Fas介导的细胞凋亡，在干扰素-g存在的情况下，这种作用被增强。所有这些检查都适用于前列腺癌。

To begin with, we have done the clinical study of the prostatic cancer in our institute and reported the results. Because of small number of cases with low stage prostatic cancer, we could not examine thoroughly the expression of c-myc or c-fos oncogene or mutation of bcl-2 gene in the resected specimen. AT6.3 is a highly metastatic rat prostatic cancer cell line. We have reported the inhibitory effects of TNP-470, an angiogenesis inhibitor, on the lung metastasis of AT6.3 cells. We also found that human prostatic cancer cell lines, LNCap, DU145 and PC3 secrete an inhibitory activity on osteoblast-differentiation. The project of purifying this activity is now going on. Because we could not obtain materials from many cases of prostatic cancer, we examined the same kind of genetic alterations in other urological tumors such as renal cell carcinoma and testicular tumors which we often find at our institute. Genomic imprinting is a new entity of genetic regulation, in which certain genes such as insulin-like growth factor II (IGF2) and H19 genes are expressed only from unilateral allele. We found that IGF2 and H19 genes are very frequently expressed from unilateral allele in testicular cancers. This genetic alteration is now under investigation on prostatic cancer. Apoptosis is a new concept of cell death, and it is typically induced through Fas-Fas ligand pathway in many cells. Prostatic cancer cells do not show the typical apoptosis through the stimulation with Fas-pathway. On the contrary, renal cell carcinoma express Fas antigen, and showed typical Fas-mediated apoptosis, which was enhanced by incubating in the presence of interferon-g. All these examinations can be applied to prostatic cancer.