Abstract
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.
Highlights
Gastric carcinoma is one of the most prevalent cancers worldwide, and constitutes a leading cause of cancer mortality in certain areas, including Korea, Japan, China, South America, and Eastern Europe (Correa, 1985, 1988)
In order to obviate the effects of individual variations in gene expression, pairs of primary gastric adenocarcinoma and matched normal mucosa from the same individual were surgically resected from patients' stomachs
As altered gene expression is a common feature of neoplastic cells, multiple genes have been reported to be differentially expressed in tumor tissues
Summary
Gastric carcinoma is one of the most prevalent cancers worldwide, and constitutes a leading cause of cancer mortality in certain areas, including Korea, Japan, China, South America, and Eastern Europe (Correa, 1985, 1988). According to the classifications established by Lauren, gastric carcinoma can be divided into diffuse (poorly differentiated)- or intestinal (well differentiated)-type adenocarcinomas. Intestinal-type tumors develop mainly in glandular formations lined by large columnar cells, with well-defined cytoplasm and large nuclei. Diffuse-type tumors mostly manifest as small, rounded cells with smoothedged nuclei and occur in small clusters or as solitary cells, exhibiting wide and diffuse spreading (Heider et al, 1993; Dammrich et al, 1995). All stages of carcinogenesis are, in general, associated with the differential expression of genes, a process which remains largely unclear. Many studies have implicated molecular and genetic alterations in the development and progression of gastric cancer (Tahara, 1993; Fuchs and Mayer, 1995; Tahara et al, 1996)
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