Aberrant methylation impairs low density lipoprotein receptor-related protein IB tumor suppressor function in gastric cancer

DNA methylation plays a significant role in tumor progression. In this study, we used CpG microarray and differential methylation hybridization approaches to identify low density lipoprotein receptor-related protein IB (LRP/B) as a novel epigenetic target in gastric cancer. LRP/B was hypermethylated In four gastric cancer cell lines, and low LRP/B m RNA expression was associated with high methylation levels in gastric cancer cell lines. Addition of a DNA methylation inhibitor (5-Aza-dC) restored the mRNA expression of LRP/B in these cell lines, indicating that DNA methylation is involved in regulating LRP/B expression. in 45 out of 74 (61%) clinical samples, LRP/B was highly methylated; LRP/B mRNA expression was significantly lower In IS out of 19 (79%, P < 0.001) gastric tumor tissues than in corresponding adjacent normal tissues. In addition, ectopic expression of mLRPIB4 in gastric cancer cell lines suppressed cell growth, colony formation and tumor formation in nude mice. These results collectively indicate that LRP/B is a functional tumor suppressor gene in gastric cancer and that is regulated by DNA methylation.