Methylation-associated silencing of TU3A in human cancers

  • Authors: Yasuo Awakura, Eijiro Nakamura, Noriyuki Ito, Toshiyuki Kamoto, Osamu Ogawa
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  • Published online on: Wednesday, October 1, 2008
  • Pages: 893-899
  • DOI: 10.3892/ijo_00000078

Abstract

TU3A, located on 3p21.1, was originally identified as a candidate tumor suppressor gene in renal cell carcinoma (RCC). Recently, down-regulation of TU3A expression has been reported not only in RCC but also in other types of cancers. However, no studies have evaluated the mechanism underlying TU3A inactivation. In the present study, we first examined the expression and promoter CpG island methylation of TU3A in RCC. TU3A mRNA was slightly or not expressed in 3 RCC cell lines (ACHN, Caki-1 and NC65). Bisulfite sequencing of the TU3A promoter and treatment of the RCC cell lines with 5-aza-2'-deoxycytidine and/or trichostatin A revealed an association between TU3A expression and promoter hypermethylation. Next, we analyzed TU3A methylation in primary RCC by using combined bisulfite restriction analysis. Mean methylated fraction was 19.2% (range: 0-57.3%) in 53 conventional RCCs and 2.3% (range: 0-12.7%) in 24 corresponding normal kidneys. We defined a methylation fraction of >20% as hypermethylation. TU3A hypermethylation was detected in 22 (41.5%) of 53 RCCs and significantly associated with advanced tumor stage (>T2 vs. T1 and T2: P=0.005, ≥N1 or M1 vs. N0M0: P=0.001) and poor disease-specific survival (P=0.0038). Furthermore, we observed promoter hyper-methylation of TU3A in several types of cancer cell lines and primary cancers of the bladder and testis. To our knowledge, the present study is the first to demonstrate the epigenetic inactivation of TU3A in human cancers. The findings of this study warrant further study to investigate the role of TU3A methylation in cancer development.
Journal Cover

October 2008
Volume 33 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.773
Ranked #31/196 Oncology
(total number of cites)

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APA
Awakura, Y., Nakamura, E., Ito, N., Kamoto, T., & Ogawa, O. (2008). Methylation-associated silencing of TU3A in human cancers. International Journal of Oncology, 33(4), 893-899.
MLA
Awakura, Nakamura, Ito, Kamoto, and Osamu Ogawa. "Methylation-associated silencing of TU3A in human cancers." International Journal of Oncology International Journal of Oncology 33.4 (2008): 893-899.
Chicago
Awakura, Nakamura, Ito, Kamoto, and Osamu Ogawa. "Methylation-associated silencing of TU3A in human cancers." International Journal of Oncology International Journal of Oncology 33 no. 4 (2008): 893-899.