Aberrant Promoter CpG Island Methylation of the hDAB2IP Gene in Colorectal Cancer

Abstract

Human DAB2IP (hDAB2IP), a novel GTPase-activating protein modulating Ras-mediated signaling, is a candidate tumor suppressor gene. However, promoter methylation of hDAB2IP in colorectal cancer (CRC) is poorly understood. To ascertain the mechanism of gene promoter hypermethylation in CRC cells, we investigated the promoter methylation status of hDAB2IP genes in four CRC cell lines using a methylation specific polymerase chain reaction (MS-PCR). The frequency of DNA methylation was detected in three of the four CRC cell lines. The hDAB2IP gene expression was examined and determined using a reverse transcription-PCR (RT-PCR) and immunoblot analysis in CRC cell lines. Gene expression was silenced or down-regulated in SW-480 with methylated hDAB2IP, but could be restored by treatment with 5-aza-2?-deoxycytidine, a DNA methyl-transferase inhibitor. The frequency of DNA methylation was detected in 10 of 25 colon tumors (40%), compared with 0 of 25 (0%) corresponding adjacent normal colon tissues (pB0.005). These results suggest that hDAB2IP methylation is frequently present in colon cancer, and gene silencing may play an important role in colorectal carcinogenesis.