Downregulation of regenerating islet-derived 3 alpha (REG3A) in primary human gastric adenocarcinomas

Gastric carcinoma is considered to be one of the most prevalent cancers worldwide. We have performed differential-display polymerase chain reaction (DD-PCR) in order to compare the gene expression profile of gastric carcinoma and that of a normal stomach, in an attempt to identifiy differentially expressed genes associated with primary human gastric cancers. One of the down-regulated genes in gastric cancers was identified as regenerating islet-derived 3 alpha (REG3A), also known as hepatocarcinoma-intestine-pancreas/ pancreatitis-associated protein (HIP/PAP). REG3A exhibited relatively high expression levels in normal gastric mucosa. However, REG3A was found to be down-regulated in 67% (20 out of 30 samples) of primary human gastric cancers, as determined by RT-PCR. In addition, REG3A mRNA expression was not detected in stomach cancer cell lines, SNU cells. Immunohistochemical analysis further confirmed the down-regulation of REG3A expression in primary human gastric cancers. Treatment with the demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-dC) resulted in the restoration of REG3A mRNA expression in the gastric cancer cell line, indicating that the transcriptional silencing of REG3A in SNU cell lines was caused by DNA methylation. Taken together, these data indicate that REG3A is down-regulated in most primary human gastric cancer cells, and might be useful in the diagnosis of gastric cancer. Further characterization of the differentially expressed gene, REG3A, should lead to a better understanding of the changes occurring at the molecular level during the development and progression of primary human gastric cancer.