Involvement of SET in the Wnt signaling pathway and the development of human colorectal cancer.

The SET oncoprotein is involved in cancer progression by modulating multiple cellular processes, including the inhibition of the tumor suppressor, protein phosphatase 2 (PP2A). Based upon these multiple activities, we hypothesized that targeted inhibition of SET is likely to have multiple discrete and measurable effects on cancer cells. In the present study, the mRNA expression levels of , and - were examined in 31 pairs of human colorectal adenocarcinoma tissues and corresponding adjacent normal colorectal tissues by quantitative real-time polymerase chain reaction (qPCR). A small interfering RNA targeting was transfected into the human colon carcinoma cell lines, LS174T and SW480. The mRNA levels of -, , and were determined by qPCR analysis and the protein levels of SET, c-Myc, PP2A and β-catenin were examined by western blot analysis. mRNA expression levels of and were found to be elevated in 22 (70.9%) samples, while PP2A expression levels were upregulated in eight (25.8%) samples. In addition, the knockdown of mRNA expression caused the upregulation of and in the two cell lines, whereas and mRNA expression was downregulated. Consistent with these results, the protein expression of β-catenin and c-Myc was found to be downregulated, whereas PP2A was upregulated at the protein level. Based on these results, we proposed that SET is essential in the carcinogenesis of human colorectal adenocarcinoma. In addition, it is suggested that SET promotes carcinogenesis through regulation of the Wnt signaling pathway.