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Gene Is Associated with 5' CpG Island Hypermethylation in Human Cancers1
First Department of Internal Medicine, Sapporo Medical University, Sapporo 060-8543, Japan
The cell cycle checkpoint plays an important role in maintaining the
integrity of cells. Recently, one of the 14-3-3 protein family members,
14-3-3
, was shown to be regulated by
p53 and to play a role in the G2-M-phase
checkpoint. To determine whether 14-3-3 is inactivated
in human cancers, the methylation status of the 5' region of
14-3-3 was investigated in a series of gastric,
colorectal, and hepatocellular cancer cell lines. Of 22 cell lines
examined, 6 showed aberrant methylation. The methylation status of
14-3-3 was found to be correlated with loss of
expression, which was restored by 5-aza-2'-deoxycytidine treatment.
Furthermore, normal G2 arrest after DNA damage was not
demonstrated in the cell lines with methylation. In primary gastric
cancers, 14-3-3 hypermethylation was observed frequently
in 26 of 60 (43%) cases and observed more frequently in poorly
differentiated adenocarcinomas (P = 0.0017). Our
findings suggest that 14-3-3 is inactivated by aberrant
methylation of the 5' region in various human cancers and that it might
play an important role in the development of undifferentiated gastric
cancers.
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