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The Role and Regulatory Mechanism of 14-3-3 Sigma in Human Breast Cancer

 SeungSang Ko  ;  Ji Young Kim  ;  Joon Jeong  ;  Jong Eun Lee  ;  Woo Ick Yang  ;  Woo Hee Jung 
 JOURNAL OF BREAST CANCER, Vol.17(3) : 207-218, 2014 
Journal Title
Issue Date
Breast neoplasms ; Estrogen-responsive finger protein ; Methylation ; SFN protein
PURPOSE: 14-3-3 sigma (σ) is considered to be an important tumor suppressor and decreased expression of the same has been reported in many malignant tumors by hypermethylation at its promoter or ubiquitin-mediated proteolysis by estrogen-responsive ring finger protein (Efp). In this study, we investigated the significance of 14-3-3 σ expression in human breast cancer and its regulatory mechanism. METHODS: Efp was silenced using small interfering RNA (siRNA) in the MCF-7 breast cancer cell line in order to examine its influence on the level of 14-3-3 σ protein. The methylation status of the 14-3-3 σ promoter was also evaluated by methylation-specific polymerase chain reaction (PCR). The expression of Efp and 14-3-3 σ in 220 human breast carcinoma tissues was assessed by immunohistochemistry. Other clinicopathological parameters were also evaluated. RESULTS: Silencing Efp in the MCF-7 breast cancer cell line resulted in increased expression of 14-3-3 σ. The Efp-positive human breast cancers were more frequently 14-3-3 σ-negative (60.5% vs. 39.5%). Hypermethylation of 14-3-3 σ was common (64.9%) and had an inverse association with 14-3-3 σ positivity (p=0.072). Positive 14-3-3 σ expression was significantly correlated with poor prognosis: disease-free survival (p=0.008) and disease-specific survival (p=0.009). CONCLUSION: Our data suggests that in human breast cancer, the regulation of 14-3-3 σ may involve two mechanisms: ubiquitin-mediated proteolysis by Efp and downregulation by hypermethylation. However, the inactivation of 14-3-3 σ is probably achieved mainly by hypermethylation. Interestingly, 14-3-3 σ turned out to be a very significant poor prognostic indicator, which is in contrast to its previously known function as a tumor suppressor, suggesting a different role of 14-3-3 σ in breast cancer.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
Jung, Woo Hee(정우희)
Jeong, Joon(정준) ORCID logo https://orcid.org/0000-0003-0397-0005
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