1. Methylation of the CDX2 promoter in Helicobacter pylori-infected gastric mucosa increases with age and its rapid demethylation in gastric tumors is associated with upregulated gene expression
- Author
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Seon-Young Kim, Keeok Haam, Kyu-Sang Song, Yong Sung Kim, Hyun Yong Jeong, Jeong-Hwan Kim, Hee-Jin Kim, Hay-Ran Jang, Jong-Lyul Park, Mirang Kim, Dong Hyuck Bae, and Eun-Hye Seo
- Subjects
0301 basic medicine ,Adult ,Male ,Cancer Research ,medicine.disease_cause ,Chromatin remodeling ,03 medical and health sciences ,0302 clinical medicine ,Stomach Neoplasms ,Cell Line, Tumor ,medicine ,Gastric mucosa ,Humans ,CDX2 Transcription Factor ,Epigenetics ,Gene Silencing ,CDX2 ,Promoter Regions, Genetic ,Aged ,biology ,Helicobacter pylori ,digestive, oral, and skin physiology ,Age Factors ,Intestinal metaplasia ,General Medicine ,Methylation ,DNA Methylation ,Middle Aged ,biology.organism_classification ,medicine.disease ,digestive system diseases ,Up-Regulation ,DNA Demethylation ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,medicine.anatomical_structure ,Gastric Mucosa ,030220 oncology & carcinogenesis ,embryonic structures ,Cancer research ,Female ,Carcinogenesis - Abstract
Pathological changes in the epigenetic landscape of chromatin are hallmarks of cancer. The caudal-type homeobox gene CDX2 is not expressed in normal gastric epithelia but rather in adult intestinal epithelia, and it is overexpressed in intestinal metaplasia (IM). However, it remains unclear how CDX2 transcription is suppressed in normal gastric epithelial cells and overexpressed in IM. Here, we demonstrate that methylation of the CDX2 promoter increases with age in Helicobacter pylori-positive, noncancerous gastric tissue, whereas the promoter is demethylated in paired gastric tumors in which CDX2 is upregulated. Moreover, we also found that the CDX2 promoter is demethylated in IM as well as gastric tumor. Immunohistochemistry revealed that CDX2 is present in foci of parts of the gastric mucosae but highly expressed in IM as well as in gastric tumors, suggesting that the elevated level of CDX2 in IM and gastric tumors may be attributable to promoter demethylation. Our data suggest that CDX2 repression may be associated with promoter methylation in noncancerous H. pylori-positive mucosa but its upregulation might be attributable to increased promoter activity mediated by chromatin remodeling during gastric carcinogenesis.
- Published
- 2020