Repositorio UFRO · Omeka S

AKT/mTOR substrate P70S6K is frequently phosphorylated in gallbladder cancer tissue and cell lines

Primer Autor	Roa, Juan C.
Co-autores	Leal, Pamela Garcia, Patricia Sandoval, Alejandra Buchegger, Kurt Weber, Helga Tapia, Oscar
Título	AKT/mTOR substrate P70S6K is frequently phosphorylated in gallbladder cancer tissue and cell lines
Editorial	DOVE MEDICAL PRESS LTD
Revista	ONCOTARGETS AND THERAPY
Lenguaje	en
Resumen	Background: Gallbladder carcinoma is a highly malignant tumor and a public health problem in some parts of the world. It is characterized by a poor prognosis and its resistance to radio and chemotherapy. There is an urgent need to develop novel therapeutic alternatives for the treatment of gallbladder carcinoma. The mammalian target of the rapamycin (mTOR) signaling pathway is activated in about 50% of human malignancies, and its role in gallbladder carcinoma has previously been suggested. In the present study, we investigated the phosphorylation status of the mTOR substrate p70S6K in preneoplastic and neoplastic gallbladder tissues and evaluated the effect of three mTOR inhibitors on cell growth and migration in gallbladder carcinoma cell lines. Methods: Immunohistochemical staining of phospho-p70S6K was analyzed in 181 gallbladder carcinoma cases, classified according to lesion type as dysplasia, early carcinoma, or advanced carcinoma. Protein expression of AKT/mTOR members was also evaluated in eight gallbladder carcinoma cell lines by Western blot analysis. We selected two gallbladder carcinoma cell lines (G415 and TGBC-2TKB) to evaluate the effect of rapamycin, RAD001, and AZD8055 on cell viability, cell migration, and protein expression. Results: Our results showed that phospho-p70S6K is highly expressed in dysplasia (66.7%, 12/18), early cancer (84.6%, 22/26), and advanced cancer (88.3%, 121/137). No statistical correlation was observed between phospho-p70S6K status and any clinical or pathological features, including age, gender, ethnicity, wall infiltration level, or histological differentiation (P < 0.05). In vitro treatment with rapamycin, RAD001, and AZD8055 reduced cell growth, cell migration, and phospho-p70S6K expression significantly in G-415 and TGBC-2TKB cancer cells (P < 0.001). Conclusion: Our findings confirm the upregulation of this signaling pathway in gallbladder carcinoma and provide a rationale for the potential use of mTOR inhibitors as a therapeutic strategy for human gallbladder carcinoma.
Tipo de Recurso	Artículo original
Description	This work was supported by FONDECYT (National Fund for Scientific and Technological Development) (grant 1090171) and DIUFRO (Research Office of Universidad de La Frontera) (project DI11-0039). Este trabajo fue financiado por FONDECYT (Fondo Nacional de Desarrollo Científico y Tecnológico) (subvención 1090171) y DIUFRO (Oficina de Investigación de la Universidad de La Frontera) (proyecto DI11-0039).
doi	10.2147/OTT.S46897
Formato Recurso	pdf
Palabras Claves	gallbladder cancer p70S6K mTOR inhibitor AKT migration cell line BILIARY-TRACT CANCER PHASE-II TRIAL OVARIAN-CANCER MAMMALIAN TARGET PROSTATE-CANCER IMMUNOHISTOCHEMICAL EXPRESSION CYCLE PROGRESSION KINASE INHIBITOR MTOR INHIBITION BREAST-CANCER cáncer de vesícula biliar p70S6K inhibidor de mTOR AKT migración línea celular CÁNCER DE VÍAS BILIARES ENSAYO DE FASE II CÁNCER DE OVARIO OBJETIVO EN MAMÍFEROS CÁNCER DE PRÓSTATA EXPRESIÓN INMUNOHISTOQUÍMICA PROGRESIÓN DEL CICLO INHIBIDOR DE QUINASA INHIBICIÓN DE MTOR CÁNCER DE MAMA
Ubicación del archivo	http://dx.doi.org/10.2147/OTT.S46897
Materias	gallbladder cancer p70S6K mTOR inhibitor AKT migration cell line BILIARY-TRACT CANCER PHASE-II TRIAL OVARIAN-CANCER MAMMALIAN TARGET PROSTATE-CANCER IMMUNOHISTOCHEMICAL EXPRESSION CYCLE PROGRESSION KINASE INHIBITOR MTOR INHIBITION BREAST-CANCER cáncer de vesícula biliar p70S6K inhibidor de mTOR AKT migración línea celular CÁNCER DE VÍAS BILIARES ENSAYO DE FASE II CÁNCER DE OVARIO OBJETIVO EN MAMÍFEROS CÁNCER DE PRÓSTATA EXPRESIÓN INMUNOHISTOQUÍMICA PROGRESIÓN DEL CICLO INHIBIDOR DE QUINASA INHIBICIÓN DE MTOR CÁNCER DE MAMA
Disciplinas de la OCDE	Biología Celular Farmacología y Farmacia Oncología
Título de la cita (Recomendado-único)	AKT/mTOR substrate P70S6K is frequently phosphorylated in gallbladder cancer tissue and cell lines
Revista/Libro	ONCOTARGETS AND THERAPY
Tipo de ruta	dorada verde
Access Rights	acceso abierto
Derechos de acceso	acceso abierto
License	CC BY NC 3.0
Condición de la licencia (Recomendado-repetible)	CC BY NC 3.0
Identificador alternativo	PMID 24124380
Idioma	en
Identificador del recurso (Mandatado-único)	Artículo original
Versión del recurso (Recomendado-único)	versión publicada
Entidad financiadora	ANID CONICYT fondecyt 1090171#UFRO DI11-0039
Referencia del Financiador (Mandatado si es aplicable-repetible)	ANID CONICYT fondecyt 1090171 UFRO DI11-0039
Editorial	DOVE MEDICAL PRESS LTD
ISSN	1178-6930
Página de inicio (Recomendado-único)	1373
Página final (Recomendado-único)	1384
Categoría WOS	Biotecnología y Microbiología Aplicada Oncología Biotechnology & Applied Microbiology Oncology
Formato	pdf
Id de Web of Science	WOS:000325061300001