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

与骨转移和表型变化相关的前列腺癌基因改变。

基本信息

批准号：
07671722
负责人：
NONOMURA Norio
金额：
$ 1.22万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

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.

开始，我们在我所进行了前列腺癌的临床研究，并报告了结果。由于前列腺癌分期较低，手术切除标本中c-myc、c-fos癌基因表达及bcl-2基因突变情况较少，不能全面检测。AT 6.3是一种高转移性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，人前列腺癌细胞系，LNCap，DU 145和PC 3分泌成骨细胞分化的抑制活性。由于我们无法从许多前列腺癌病例中获得材料，因此我们检测了在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）中的相同基因改变。基因组印记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（IGF 2）和H19基因仅在单侧等位基因中表达。我们发现IGF 2和H19基因在睾丸癌中非常频繁地由单侧等位基因表达。这种基因改变目前正在研究前列腺癌。细胞凋亡是细胞死亡的一个新概念，在许多细胞中，细胞凋亡是通过Fas-Fas配体途径诱导的。前列腺癌细胞在Fas信号通路的刺激下并不表现出典型的凋亡。相反，肾细胞癌表达Fas抗原，并表现出典型的Fas介导的凋亡，在干扰素-g存在下孵育增强。所有这些检查都可以应用于前列腺癌。