Overexpression of YWHAZ relates to tumor cell proliferation and malignant outcome of gastric carcinoma.
Br J Cancer
; 108(6): 1324-31, 2013 Apr 02.
Article
en En
| MEDLINE
| ID: mdl-23422756
ABSTRACT
BACKGROUND:
Several studies have demonstrated that YWHAZ (14-3-3ζ), included in the 14-3-3 family of proteins, has been implicated in the initiation and progression of cancers. We tested whether YWHAZ acted as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC).METHODS:
We analysed 7 GC cell lines and 141 primary tumours, which were curatively resected in our hospital between 2001 and 2003.RESULTS:
Overexpression of the YWHAZ protein was frequently detected in GC cell lines (six out of seven lines, 85.7%) and primary tumour samples of GC (72 out of 141 cases, 51%), and significantly correlated with larger tumour size, venous and lymphatic invasion, deeper tumour depth, and higher pathological stage and recurrence rate. Patients with YWHAZ-overexpressing tumours had worse overall survival rates than those with non-expressing tumours in both intensity and proportion expression-dependent manner. YWHAZ positivity was independently associated with a worse outcome in multivariate analysis (P=0.0491, hazard ratio 2.3 (1.003-5.304)). Knockdown of YWHAZ expression using several specific siRNAs inhibited the proliferation, migration, and invasion of YWHAZ-overexpressing GC cells. Higher expression of the YWHAZ protein was significantly associated with the lower expression of miR-375 in primary GC tissues (P=0.0047).CONCLUSION:
These findings suggest that YWHAZ has a pivotal role in tumour cell proliferation through its overexpression, and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
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Biomarcadores de Tumor
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Proteínas 14-3-3
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Proliferación Celular
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Recurrencia Local de Neoplasia
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged80
Idioma:
En
Revista:
Br J Cancer
Año:
2013
Tipo del documento:
Article
País de afiliación:
Japón