Abstract
Background: Genetic alterations of p14ARF contribute to dysfunction of p53 pathways by disruption of MDM2-mediated inhibition of p53. P14ARF was investigated by focusing on the homozygous deletion (HD) in the INK4a/ARF locus and hypermethylation of the p14ARF promoter in renal cell cancer (RCC). Materials and Methods: Using 6 RCC cell lines, RT-PCR and Western blotting was performed for p14ARF. DNA from 34 RCCs was analyzed for HD in the INK4a/ARF locus, promoter hypermethylation and p53 gene mutation. Results: HD was confirmed in 4 out of 6 cell lines and in 8 out of 34 (23.5%) RCC specimens, which correlated with the presence of metastasis, high tumor grade and had a tendency to more advanced stage (I vs. II-IV). No hypermethylation of the p14ARF promoter or p53 mutation was detected among the RCC specimens. Conclusion: These results indicate that the deletion in the INK4a/ARF locus might contribute to tumor progression in RCC at least partly by functional inactivation of wild-type p53.
Footnotes
- Received August 31, 2006.
- Revision received October 12, 2006.
- Accepted October 17, 2006.
- Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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