RESUMEN
BACKGROUND: Gallbladder cancer (GBC) is an aggressive and highly lethal biliary tract malignancy, with extremely poor prognosis. In the present study, we analyzed the potential involvement of MYBL2, a member of the Myb transcription factor family, in the carcinogenesis of human GBC. METHODS: MYBL2 expression levels were measured in GBC and cholecystitis tissue specimens using quantitative real-time PCR (qRT-PCR) and immunohistochemical (IHC) assays. The effects of MYBL2 on cell proliferation and DNA synthesis were evaluated using Cell Counting Kit-8 assay (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) retention assay, flow cytometry analysis, western blot, and a xenograft model of GBC cells in nude mice. RESULTS: MYBL2 expression was increased in GBC tissues and associated with histological differentiation, tumour invasion, clinical stage and unfavourable overall survival in GBC patients. The downregulation of MYBL2 expression resulted in the inhibition of GBC cell proliferation, and DNA replication in vitro, and the growth of xenografted tumours in nude mice. Conversely, MYBL2 overexpression resulted in the opposite effects. CONCLUSIONS: MYBL2 overexpression promotes GBC cell proliferation through the regulation of the cell cycle at the S and G2/M phase transitions. Thus, MYBL2 could serve as a potential prognostic and therapeutic biomarker in GBC patients.
Asunto(s)
Biomarcadores de Tumor/biosíntesis , Proteínas de Ciclo Celular/biosíntesis , Proliferación Celular , Neoplasias de la Vesícula Biliar , Proteínas de Neoplasias/biosíntesis , Transactivadores/biosíntesis , Anciano , Anciano de 80 o más Años , Animales , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Neoplasias de la Vesícula Biliar/metabolismo , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/patología , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
We report the low-temperature resistance upturn in sandwiched structures of La2/3Sr1/3MnO3/ZrO2/La2/3Sr1/3MnO3 and La2/3Sr1/3MnO3/LaMnO3/La2/3Sr1/3MnO3, while it disappeared when the interlayer was replaced by YBa2Cu3O7. The experimental data have been analyzed qualitatively and quantitatively. The results show that the low temperature resistance upturn is mainly due to the quantum correction effects driven by the weak localization and the electron-electron interaction in such a strongly correlated system, and the contribution of each factor varies with grain boundaries. Moreover, the resistance upturns are suppressed by a local magnetic field. These findings will help to further understand the physical mechanism of low-temperature resistance upturn in colossal magnetoresistance manganites. Furthermore, it is also helpful to reveal the intrinsic transport mechanism at the interfaces of semiconductor/ferromagnetism and antiferromagnetism/ferromagnetism.
Asunto(s)
Carcinoma Hepatocelular/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptido Hidrolasas/genética , Péptido Hidrolasas/metabolismo , Fosfoserina/metabolismo , Complejo del Señalosoma COP9 , Carcinoma Hepatocelular/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/química , Electroforesis en Gel de Poliacrilamida , Humanos , Péptidos y Proteínas de Señalización Intracelular/química , Péptido Hidrolasas/química , FosforilaciónAsunto(s)
Carcinoma Hepatocelular/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/patología , Estadificación de Neoplasias , FosforilaciónRESUMEN
BACKGROUND & OBJECTIVE: Arsenic trioxide (As(2)O(3)) is a new drug used to treat solid tumors. However, the mechanism is still unclear. This study was to investigate the effects of As(2)O(3) on the proliferation of human hepatocellular carcinoma (HCC) cell line SMMC-7721, and to explore the mechanisms. METHODS: When treated with 0-8 micromol/L As(2)O(3) for 96 h, the survival rate of SMMC-7721 cells was determined by WST-8 assay. When treated with 2 micromol/L As(2)O(3) for 72 h, the expression of P27(kip1) and c-Jun activation domain-binding protein 1 (JAB1) in SMMC-7721 cells were detected at different time points by Western blot, the subcellular localization of P27(kip1) and JAB1 was detected by subcellular fractionation and immunofluorescent staining. RESULTS: As(2)O(3) significantly inhibited the proliferation of SMMC-7721 cells. The 50% inhibition concentration (IC50) of As(2)O(3) to SMMC-7721 cells was (1.81+/-0.41) micromol/L at 96 h. When SMMC-7721 cells were treated with 2 mumol/L As(2)O(3) for 12 h, the expression of JAB1 was down-regulated and that of P27kip1 was up-regulated. Furthermore, P27(kip1) and JAB1 proteins were translocated from the cytoplasm into nuclei when cells were exposed to 2 micromol/L As(2)O(3) for 12 h and 24 h, respectively. The nuclear accumulation of both proteins was also observed under fluorescence microscope after treatment of 2 micromol/L As(2)O(3). CONCLUSION: As(2)O(3) attenuates JAB1 expression, thereby disturbs the location and expression of P27(kip1), and may participate in regulating the proliferation of SMMC-7721 cells through interfering with the function of P27(kip1).