Significance of newly identified apoptosis-related p19^<ARF> gene alteration in Urological tumors.

p19^<ARF>（p14^<ARF>）结合并抑制MDM 2功能，导致p53作为基因组监护人的良好功能。本课题研究了p14^在泌尿系肿瘤中的基因表达状况和功能<ARF>，主要结果如下：1.在移行细胞癌细胞系中，RT 4没有表明纯合缺失（HD）的mRNA。2. 4种肾癌细胞株中，ACHN和KRC/Y表达p14 <ARF>mRNA.采用定量DNA-PCR检测HD，提示3株RCC细胞系存在HD. p14 α免疫组化染色<ABF>，3种抗体在肾细胞癌组织中均未检测到阳性表达. 34例肿瘤标本中8例DNA呈HD型，且细胞增殖较差.在<AEF>缺陷细胞系中导入p14^基因导致致死，并且显示p14^ mRNA阳性的一个稳定转染子<ARF>不具有任何蛋白，表明存在使p14^功能失活的表观遗传机制<AHF>。因此，显示罕见的p53基因改变的RCC可能<ARF>由于HD或表观遗传机制的失活而携带p14^的功能障碍。

p19^<ARF> (p14^<ARF> in human) binds and inhibits MDM2 function leading to sound function of p53 as a guardian of genome. In this project we have investigated gene status and function of p14^<ARF> in Urological tumors, and obtained results as follows :1. Among transitional cell cancer cell lines, RT4 did not have mRNA suggesting homozygous deletion (HD).2. Out of 4 renal cell carcinoma (RCC) cell lines, ACHN and KRC/Y expressed p14^<ARF> mRNA.3. Using quantitative DNA-PCR evaluating HD, 3 RCC cell lines were suggested to have HD.4. Immunihistochemical staining for p14^<ABF> using 3 different antibodies, no positive staining was detected in RCC samples.5. Eight of thirty-four DNA extracted for tumor specimens revealed HD pattern and also poorer prognosis.6. Introduction of p14^<AEF> gene in deficient cell lines resulted in lethal, and one stable transfectant showing p14^<ARF> mRNA positivity did not have any protein, indicating presence of epigenetic mechanism inactivating p14^<AHF> function. Thus, RCC showing infrequent p53 gene alteration may carry malfunction of p14^<ARF> because of HD or inactivation by epigenetical mechanism(s).