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The p14(ARF) and p16(INK4A) tumor suppressor genes are commonly inactivated by aberrant methylation of their promoter regions in human colon cancer. The methyl-CpG-binding domain protein MBD2 is physically associated with the methylated promoters of the p14(ARF) and p16(INK4A) genes in specific tumor cell lines. Moreover, deficiency of MBD2 strongly inhibits intestinal tumorigenesis in the Min mouse, raising the possibility that the protein might be involved in transcriptional repression of methylated tumor suppressor genes. The aim of this study was to evaluate the role of MBD2 in the silencing of p14(ARF) and p16(INK4A) in cancer.

MBD2-Mediated Transcriptional Repression of the <i>p14</i><sup>ARF</sup> Tumor Suppressor Gene in Human Colon Cancer Cells