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The Tumor Suppressor Gene 14-3-3 Is Commonly Methylated in Normal and Malignant Lymphoid Cells

KFNCCC&R, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, 11211

14-3-3 /Stratifin was first identified as an epithelial cell antigen (HME-1) exclusively expressed in epithelia. However, the functional role of in cell proliferation and apoptosis would suggest that this protein could be relevant to the regulation of growth and differentiation of multiple cell types. Recent evidence demonstrates that acts as a tumor suppressor gene that is inactivated by methylation of its 5' CpG islands in epithelial tumor cells. In normal epithelia, is commonly unmethylated. The objective of this study was to determine the methylation status of in lymphoid cells. We now demonstrate by methylation-specific PCR analysis that is also methylated in normal and malignant lymphocytes. Such methylation, however, fails to completely silence its expression. Compared with the robust expression in epithelial cells, lymphocytes showed basal, but clearly evident, levels of as determined by reverse transcription-PCR and Western blot. The finding of 5' region methylation in lymphocytes has direct implications in the use of body fluids on methylation tests for noninvasive monitoring of occult epithelial tumor cells and suggests that may not be an adequate biomarker for methylation-specific PCR analysis.

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