The Expression Of DUSP6 In ESCC And The Mechanism Of Its Inhibition Effect On Tumors

DUSP6, a pivotal negative feedback regulator of the RAS-ERK pathway, showed a low expression profile in esophageal squamous cell carcinoma (ESCC) tissues in our studies. In primary esophageal cancers, DUSP6 expression levels decreased as both clinical TMN grade and histological grade of the tumor increased. We found that the DUSP6 expression levels was also relatively weak in the EC9706 and KYSE150 ESCC cell lines, while the p-ERK was overexpressed in the ESCC cell lines and the ESCC tissues. We treated the cells with 5-Aza-2’-deoxycytidine, then we observed a notable expression of DUSP6 in both EC9706 and KYSE150 cell lines. The MS-PCR, methylation specific PCR, results showed the CpG islands were hypermethylated in DUSP6 intron 1. Interestingly, the p-ERK expression was dramatically suppressed after the transfection of DUSP6 gene. At the same time, we observed the transfection lead to the apoptosis of the tumor cells. The mechanism of the apoptosis induced by DUSP6 was demonstrated involved in caspase-PARP pathway. In our study, we not only confirmed the low expression both in the primary ESCC tissues and cell lines, but also proved the relationship between DUSP6 and ERK. Meanwhile, we confirmed the mechanism of the low DUSP6 expression was because of the hypermethylation of intron 1 of DUSP6. Our study indicated that DUSP6 expression tracked in tandem with ERK inhibition, which gave rise to the apoptosis of the tumor cells. Further studies assessing the tumor suppressive role of DUSP6 and strategies aimed at modulation of its activity are warranted.