COX-2 gene expression and methylation profile in Sapajus apella as an experimental model for gastric adenocarcinoma.

Abstract

Gastric cancer (GC) remains one of the main causes of cancer-related death worldwide. There are two distinct histological types of GC: diffuse and intestinal. The latter is characterized by the presence of pre-neoplastic lesions. One of the most frequently altered enzymes in intestinal GC is COX-2, an important lesion marker. This work aimed to study COX-2 methylation and expression in N-methyl-N-Nitrosurea (MNU)-induced intestinal GC in six Sapajus apella animals. The partial promoter sequence of S. apella COX-2 gene was obtained and used to identify transcription factors and cis-regulatory element binding sites. The COX-2 methylation pattern was assessed using Methylation-Specific PCR (MSP), and expression was analyzed by immunohistochemistry (IHQ). A total of 20 samples were obtained. A 675 bp fragment of the S. apella COX-2 promoter region was obtained, and it was 99.2% and 68.2% similar to H. sapiens and S. boliviensis, respectively. Similar to humans, several transcription factors and cis-regulatory element binding sites were identified in the S. apella sequence. MSP revealed that all samples were methylated. However, IHQ results demonstrated positive COX-2 expression in all pre-neoplastic and tumoral samples. The results suggest that the analyzed fragment is not crucial in COX-2 regulation of GC in S. apella.