Frequent reduced expression of alpha-1B-adrenergic receptor caused by aberrant promoter methylation in gastric cancers

Abstract

Recent studies have suggested that epigenetic inactivation of tumour-related genes by promoter methylation participates in the development of gastric cancer. We newly identified the frequently aberrant promoter methylation of alpha-1B-adrenergic receptor (ADRA1B) in colorectal cancer by methylation-sensitive representational difference analysis (MS-RDA) and examined the methylation status of the ADRA1B promoter in 34 paired samples of colorectal cancer and surrounding epithelial tissue, and 34 paired samples of gastric cancer and surrounding epithelial tissue. In colorectal cancers, only four of 34 (11.8%) tumours showed ADRA1B promoter methylation. In contrast, ADRA1B promoter methylation was detected in 24 of 34 (70.6%) gastric cancers and in 14 of 34 (41.2%) surrounding epithelial tissues. The frequency of ADRA1B promoter methylation was higher in gastric epithelial tissues with intestinal metaplasia (41.6%) than in those without intestinal metaplasia (25.0%). Reverse transcription -PCR detected reduced ADRA1B expression in 12 of 18 (66.7%) gastric cancers, and its promoter methylation was detected in 11 of these 12 (91.7%) gastric cancers with reduced ADRA1B expression. Thus, ADRA1B promoter is frequently methylated in gastric cancer. Our results suggest that the ADRA1B gene is an important tumour-related gene frequently involved in the development and progression of gastric cancer.

Identification and Validation of Immune Cells and Hub Genes in Gastric Cancer Microenvironment

“…ADRA1B is a member of the GPCRs, and it has been reported that this gene is closely related to the prognosis of thyroid papillary carcinoma [ 47 ]. Studies have shown that the methylation of ADRA1B plays a key role in the occurrence and development of GC [ 48 , 49 ]. Our study showed that the expression of ADRA1B in GC tissues was lower than that in adjacent tissues, which may be related to methylation.…”

p16 gene methylation in colorectal cancer patients with long-term follow-up

“…It is one of the cancers with better characterised tumorogenesis genetic pathways and one of the common alterations implicated in tumorogenesis is DNA methylation (20). Promoter methylation silences tumor suppressor genes in great number of neoplasias (21,22). p16 gene acts as a negative controller of cell cycle playing an important role as tumor suppressor (23).…”

Promoter hypermethylation of tumor‐related genes in peritoneal lavage and the prognosis of patients with colorectal cancer

“…The aberrant methylation of gene promoters is a major mechanism for silencing tumor suppressors or other cancer-associated genes in many kinds of human cancers [16][17][18]. Genes such as CDH1, p16, MGMT, and APC have been found to harbor hypermethylated promoters in over 30% of colorectal tumors [19][20][21][22].…”