Abstract:

Objective To investigate the insulin-like growth factor binding protein 7 (IGFBP7) gene expressions in gastric cancer cell lines and methylation regulation. Methods Four gastric cancer cell lines, high-differentiated MKN28, middle-differentiated SGC-7901 and AGS, poorly differentiated MKN-45, and normal gastric epithelial cell line (GES-1) were cultured. The IGFBP7 mRNA expressions in different cell lines were detected by RT-PCR. The DNA methylation status was assayed by methylation-specific PCR (MSP). Gastric cancer cell line was treated with DNA methyltransferase inhibitor, 5'-aza-2'-deoxycytidine (5-aza-dc). And the IGFBP7  mRNA expression was detected using real-time PCR. Results Compared with the GES-1, the expression of the IGFBP7  mRNA decreased or disappeared in gastric cell lines. Through the MSP, the aberrant methylation of IGFBP7 mRNA in exon 1 was found. After the 5-aza-dc treatment, the IGFBP7 expression was up-regulated dose-dependently. Conclusion Hypermethylation is responsible for the tumor-specific loss of IGFBP7 gene expression. Treatment with a demethylating agent, 5-aza-dc, can lead to the reexpression of IGFBP7 mRNA in the gastric cancer cell lines. It suggests an important role of hypermethylation in the loss of IGFBP7 mRNA expression.

Key words: insulin-like growth factor binding protein 7 gene, gastric cancer cell lines, methylation