A study was performed to evaluate the significance of aberrations of the newly identified
DNA demethylase, MBD2, in human
carcinogenesis. Levels of expression of
DNA demethylase
mRNA were examined by reverse transcription followed by real-time quantitative detection of the PCR products in 32 samples of
colorectal cancer tissue, 24
stomach cancers, and the corresponding noncancerous mucosae.
DNA demethylase
mRNA levels normalized with
glyceraldehydephosphate dehydrogenase (GAPDH)
mRNA were reduced in 31 (97%) of the 32
colorectal cancers and in 22 (92%) of the 24
stomach cancers when compared with the levels in the corresponding noncancerous mucosae. The average levels of
DNA demethylase
mRNA expression normalized with GAPDH
mRNA in each of the colorectal (0.81 +/- 0.55) and stomach (2.88 +/- 0.23)
cancers were significantly lower than in the noncancerous mucosae (1.90 +/- 0.16 and 5.11 +/- 0.34, respectively, p < 0.0001). There was no significant association between the
DNA demethylase
mRNA level and malignant potential in both colorectal and
stomach cancers. These data suggest that reduced expression of
DNA demethylase may play a role at a certain step of multistage
carcinogenesis. Reduction of
DNA demethylase
mRNA expression may be, if anything, one of the early events of
carcinogenesis, but may not participate in the malignant progression of
tumors.