Discussion selleck chem In the current study, we found that the expression level of DACT2 was downregulated in human hepatocellular carcinoma by quantitative RT PCR and immunohisto chemical analysis. Similarly, in a previous study, Jiang et al. also found that DACT2 expression is also reduced in some colorectal tumors. Inhibitors,Modulators,Libraries Therefore, DACT2 was implicated as a tumor suppressor gene in some types of human cancers. We further speculate about whether the expression level of DACT2 might be associated with clinicopathological parameters in liver transplantation HCC patients. Clinicopathological analysis revealed that HCC patients with low DACT2 expression was corre lated with a larger tumor size than those with high DACT2 expression. DACT2 may thus play a critical role in the proliferation and progression of HCC cells.
To the best of our knowledge, there have been no prior reports studying the associations between DACT2 gene expression and clinicopathological parameters in human cancer. Thus, this is the first study Inhibitors,Modulators,Libraries to determine the ex pression pattern of DACT2 and report the clinical sig nificance of DACT2 gene expression in HCC. Because of the possible role of DACT2 in Inhibitors,Modulators,Libraries tumor suppression and its reduced expression in cancer, the correlation of DACT2 expression and its methylation status have been characterized in colorectal cancer. Aberrant promoter hypermethylation of DACT2 was detected in several tumor samples with reduced DACT2 expression. This finding led us to investigate the potential correl ation of expression level and promoter methylation of DACT2 in HCC.
Similar to the previous report on colon cancer cells, we found that DACT2 expression was Inhibitors,Modulators,Libraries present at very low or undetectable levels in some HCC cell lines and that 5 Aza dC restored the transcription level of DACT2. These data suggested that the downregulation of DACT2 expression was closely associated Inhibitors,Modulators,Libraries with promoter hypermethylation in vitro. Taken together, these findings further support that DACT2 is inactivated epigenetically in a number of hu man solid tumors including HCC and that promoter hypermethylation may be a critical mechanism for the transcriptional silencing of the DACT2 gene in liver can cer cell lines. The tumor suppressive function of DACT2 in HCC was investigated further by in vitro assays.
In DACT2 expression silenced MHCC97L cells, FACS analysis revealed a significant increase of S phase cells and a decrease of G0G1 phase cells, indicating G1S arrest of the cell cycle and a significant promotion reference 4 of cell prolife ration. In addition, DACT2 knockdown in MHCC97L cells also resulted in increased ability of tumor cell inva sion and metastasis. Taken together, these results suggest the role of DACT2 as a functional tumor suppressor gene through suppressing tumor cell prolife ration, migration and invasion in HCC.