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- Title
Epigenetic silencing of AXIN2 in colorectal carcinoma with microsatellite instability.
- Authors
Koinuma, K; Yamashita, Y; Liu, W; Hatanaka, H; Kurashina, K; Wada, T; Takada, S; Kaneda, R; Choi, Y L; Fujiwara, S-I; Miyakura, Y; Nagai, H; Mano, H
- Abstract
Mutation or epigenetic silencing of mismatch repair genes, such as MLH1 and MSH2, results in microsatellite instability (MSI) in the genome of a subset of colorectal carcinomas (CRCs). However, little is yet known of genes that directly contribute to tumor formation in such cancers. To characterize MSI-dependent changes in gene expression, we have now compared transcriptomes between fresh CRC specimens positive or negative for MSI (n=10 for each) with the use of high-density oligonucleotide microarrays harboring >44,000 probe sets. Correspondence analysis of the expression patterns of isolated MSI-associated genes revealed that the transcriptome of MSI+ CRCs is clearly distinct from that of MSI- CRCs. Such MSI-associated genes included that for AXIN2, an important component of the WNT signaling pathway. AXIN2 was silenced, apparently as a result of extensive methylation of its promoter region, specifically in MSI+ CRC specimens. Forced expression of AXIN2, either by treatment with 5'-azacytidine or by transfection with AXIN2 cDNA, resulted in rapid cell death in an MSI+ CRC cell line. These data indicate that epigenetic silencing of AXIN2 is specifically associated with carcinogenesis in MSI+ CRCs.
- Publication
Oncogene, 2006, Vol 25, Issue 1, p139
- ISSN
0950-9232
- Publication type
Journal Article
- DOI
10.1038/sj.onc.1209009