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

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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).