Galanin is an epigenetically silenced tumor suppressor gene in gastric cancer cells

Galanin is a 30 amino-acid active neuropeptide that acts via three G-protein coupled galanin receptors, GALR1, GALR2 and GALR3. Recently, GALR1 was also suggested as a tumor suppressor gene that was frequently silenced in head and neck squamous cell carcinoma; moreover, galanin and GALR1 were reported to inhibit human oral cancer cell proliferation. However, the exact role of galanin in gastric cancer is unclear. Here, we describe the epigenetic silencing of galanin in human gastric cancer. Five gastric cancer cell lines (SNU-1, SNU-601, SNU-638, KATOIII, and AGS) showed a significant reduction in galanin expression that was restored by the demethylating agent 5-aza-2'-deoxycytidine. We confirmed the hypermethylation of CpG islands in the galanin promoter region by methylation-specific and bisulfate sequencing polymerase chain reaction (PCR). Interestingly, hypermethylated galanin did not affect galanin receptor expression. Exogenous galanin expression in silenced cells induced apoptosis and decreased phosphorylated Akt expression. Taken together, these data suggest that galanin hypermethylation impairs its tumor suppressor function in gastric cancer carcinogenesis.