The Role and Regulatory Mechanism of 14-3-3 Sigma in Human Breast Cancer
Journal of Breast Cancer 2014³â 17±Ç 3È£ p.207 ~ p.218
°í½Â»ó(Ko Seung-Sang) - Catholic Kwandong University College of Medicine Cheil General Hospital & Women¡¯s Health Care Center Department of Surgery
±èÁö¿µ(Kim Ji-Young) - CHA University CHA Gangnam Medical Center Department of Pathology
Á¤ÁØ(Jeong Joon) - Yonsei University College of Medicine Department of Surgery
ÀÌÁ¾Àº(Lee Jong-Eun) - Yonsei University College of Medicine Department of Anatomy
¾ç¿ìÀÍ(Yang Woo-Ick) - Yonsei University College of Medicine Department of Pathology
Á¤¿ìÈñ(Jung Woo-Hee) - Yonsei University College of Medicine Department of Pathology
Abstract
Purpose: 14-3-3 sigma (¥ò) 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 ¥ò 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 ¥ò protein. The methylation status of the 14-3-3 ¥ò promoter was also evaluated by methylation-specific polymerase chain reaction (PCR). The expression of Efp and 14-3-3 ¥ò 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 ¥ò. The Efp-positive human breast cancers were more frequently 14-3-3 ¥ò-negative (60.5% vs. 39.5%). Hypermethylation of 14-3-3 ¥ò was common (64.9%) and had an inverse association with 14-3-3 ¥ò positivity (p=0.072). Positive 14-3-3 ¥ò 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 ¥ò may involve two mechanisms: ubiquitin-mediated proteolysis by Efp and downregulation by hypermethylation. However, the inactivation of 14-3-3 ¥ò is probably achieved mainly by hypermethylation. Interestingly, 14-3-3 ¥ò 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 ¥ò in breast cancer.
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Breast neoplasms, Estrogen-responsive finger protein, Methylation, SFN protein
KMID :
1134120140170030207
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