Infrequent COX-2 expression due to promoter hypermethylation in gastric cancers in Dalian, China.

摘要: Cyclooxygenase-2 (COX-2) has been shown to play oncogenic roles during stepwise gastrocarcinogenesis, and its expression is correlated with Helicobacter pylori infection, tumor necrosis factor alpha-mediated nuclear (NF)-kappaB activation, Wnt signaling. To examine COX-2 the status of regulatory factors, we examined 49 gastric cancers (GCs), 21 premalignant tissues, 10 noncancerous mucosa from residents Dalian, China. Unexpectedly, it was found that infrequent in samples (18.8%, 15/80) regardless type lesion or morphological phenotype. H infection detected 19 35 tested GC cases. Tumor alpha expression, NF-kappaB translocation, Wnt2 overexpression observed 56 (82.3%) 68, 40 (50.0%) 80, 62 (77.5%) 80 tissue samples, respectively. Methylation-sensitive restriction enzyme digestion followed by polymerase chain reaction promoter regions revealed a remarkably high hypermethylation rate (100%, 20/20) among COX-2-negative GCs, which associated DNA methyltransferase (DNMT) 1 (r = 0.587, P < .01). These results indicate (1) contrast previous findings using other sources, our show activity may not be critical molecular event formation, (2) tumor-promoting effects activities mediated COX-2-independent pathways, (3) major cause silencing Dalian apparently because increased DNMTs (especially DNMT1). Consequently, COX-2-oriented preventive therapeutic strategy practical for GCs. The frequent GCs could have insightful epigenetic epidemiologic implications.