2810

SFN

YWHAS;stratifin;SFN;stratifin

14-3-3 protein sigma|14-3-3 sigma|epithelial cell marker protein 1

1p36.11

protein-coding

Count: 1; Generif

In order to confirm the role of 14-3-3 sigma (sigma) as a tumor suppressor in breast carcinogenesis, we have studied the expression of 14-3-3sigma immunohistochemically in usual ductal hyperplasia (UDH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) breast lesions. Immunostaining for estrogen receptor alpha (ERalpha), p53 and estrogen-responsive RING finger protein (Efp) was also carried out. Immunohistochemically, expression of 14-3-3sigma was seen in 92% UDH lesions and gradually decreased from 65% in DCIS to 23% in IDC. The expression of ERalpha decreased gradually from UDH to DCIS to IDC, while p53 showed an inverse staining pattern to that of ERalpha. The expression of Efp showed no significant difference among the three breast lesions. Hence, the present immunohistochemical study confirmed 14-3-3sigma as a tumor suppressor in breast carcinogenesis. A similar immunohistochemical analysis was then carried out on columnar cell hyperplasia with atypia (CCHA), in which the expression pattern of tumor suppressor 14-3-3sigma, ERalpha and p53 suggested that it might be possible that CCHA is a precancerous lesion.

14-3-3 sigma/Stratifin was first identified as an epithelial cell antigen (HME-1) exclusively expressed in epithelia. However, the functional role of sigma 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 sigma acts as a tumor suppressor gene that is inactivated by methylation of its 5' CpG islands in epithelial tumor cells. In normal epithelia, sigma is commonly unmethylated. The objective of this study was to determine the methylation status of sigma in lymphoid cells. We now demonstrate by methylation-specific PCR analysis that sigma 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 sigma as determined by reverse transcription-PCR and Western blot. The finding of sigma 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 sigma may not be an adequate biomarker for methylation-specific PCR analysis.