The Role and Regulatory Mechanism of 14-3-3 Sigma in Human Breast Cancer / 한국유방암학회지
Journal of Breast Cancer
;
: 207-218, 2014.
Artigo
em Inglês
| WPRIM
| ID: wpr-20461
ABSTRACT
PURPOSE:
14-3-3 sigma (sigma) 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 sigma 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 sigma protein. The methylation status of the 14-3-3 sigma promoter was also evaluated by methylation-specific polymerase chain reaction (PCR). The expression of Efp and 14-3-3 sigma 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 sigma. The Efp-positive human breast cancers were more frequently 14-3-3 sigma-negative (60.5% vs. 39.5%). Hypermethylation of 14-3-3 sigma was common (64.9%) and had an inverse association with 14-3-3 sigma positivity (p=0.072). Positive 14-3-3 sigma 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 sigma may involve two mechanisms ubiquitin-mediated proteolysis by Efp and downregulation by hypermethylation. However, the inactivation of 14-3-3 sigma is probably achieved mainly by hypermethylation. Interestingly, 14-3-3 sigma 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 sigma in breast cancer.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Prognóstico
/
Mama
/
Neoplasias da Mama
/
Imuno-Histoquímica
/
Regulação para Baixo
/
Linhagem Celular
/
Reação em Cadeia da Polimerase
/
Intervalo Livre de Doença
/
RNA Interferente Pequeno
/
Proteólise
Tipo de estudo:
Estudo prognóstico
Limite:
Humanos
Idioma:
Inglês
Revista:
Journal of Breast Cancer
Ano de publicação:
2014
Tipo de documento:
Artigo
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