Browsing by Subject "P53"

Now showing 1 - 5 of 5
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    Cisplatin induced apoptosis of ovarian cancer A2780s cells by activation of ERK/p53/PUMA signals
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Song, Hao; Wei, Mei; Liu, Wenfen; Shen, Shulin; Li, Jiaqun; Wang, Liming
    Cisplatin (CDDP) is one of the most effective anticancer agents widely used in the treatment of solid tumors, including ovarian cancer. It is generally considered as a cytotoxic drug which kills cancer cells by causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, the underlying mechanisms leading to cell apoptosis remain obscure. In this study, the signaling pathways involved in CDDPinduced apoptosis were examined using CDDP-sensitive ovarian cancer A2780s cells. A2780s cells were treated with CDDP (1.5-3 μg/ml) for 6h, 12h and 24h. Using siRNA targeting P53 and PUMA, and a selective MEK inhibitor, PD98059 to examine the relation between ERK1/2 activation, p53 and PUMA expression after exposure to CDDP, and the effect on CDDP-induced apoptosis. The results shown that treatment of A2780s cells with CDDP (3 μg/ml) for 6-24h induced apoptosis, resulting in the activation of extracellular signalregulated kinase 1/2 (ERK1/2) and accumulation of p53 and PUMA (p53 upregulated modulator of apoptosis) protein. Knockdown of P53 or PUMA by siRNA transfection blocked CDDP-induced apoptosis. Inhibition of ERK1/2 using PD98059, a selective MEK inhibitor, blocked the apoptotic cell death but prevented CDDP-induced accumulation of p53 and PUMA. Knockdown of P53 by siRNA transfection also blocked CDDP-induced accumulation of PUMA. We therefore concluded that CDDP activated ERK1/2 and inducedp53-dependent PUMA upregulation, resulting in triggering apoptosis in A2780s cells. Our study clearly demonstrates that the ERK1/2/p53/PUMA axis is related to CDDP-induced cell death in A2780s cells.
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    La expresión de P53 y C-erb-2 en el carcinoma de células transicionales de pelvis y uréter y su relación con progresión tumoral y supervivencia
    (Iniestares, S.A., 2002-09-28) Fontana, Luis Óscar; García García, Felipe; Árcas Martínez Salas, Isabel; García Ligero, Julián; Tomás Ros, Mariano; Rico Galiano, José Luis; Sempere Gutiérrez, Andrés; Canteras Jordana, Manuel; Martínez Díaz, F.; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
    Resumen.- OBJETIVOS: Valorar la sobreexpresión de P53 y C-erb-2 como factor pronostico de progresión y supervivencia en pacientes con Tm. de pelvis renal y uréter. MÉTODO: Análisis retrospectivo de historias clínicas y estudios anatomopatológicos e inmunohistoquímicos de 61 pacientes sometidos a cirugía por T.U.S. El estudio inmunohistoquímico de las muestras se realizó con técni-cas de STREPTAVIDINA-BIOTINA-PEROXIDASA me-diante KIT LASAB (DAKO). El análisis de los resultados, se realizó mediante tablas de contingencias 2x2 con cálculos de Chi2 de PEARSON y análisis de residuos para variables cualitativas, el nivel de confianza fue de P<0,05, para la interrelación de variables múltiples se utilizó análisis multivariantes de COX y curvas de superviven-cias. RESULTADOS. La mayor sobreexpresión de P53 estuvo relacionada con la muerte tumor dependiente (P<0,001). Teniendo estos pacientes comprometida su superviven-cia a largo plazo. La sobreexpresión de C-erb-2 no se relaciona estadísticamente con la proliferación, ni muerte tumor dependiente de los T.U.S. CONCLUSIONES: En nuestra serie la sobreexpresión P53 es de utilidad pronóstica en los T.U.S., mientras que la expresión C-erb-2 no tuvo valor pronóstico en estos tumores.--------------------------
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    Expression of p53 and isoforms in beningn and malignant lesions of the head and neck
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Trovato, M.C.; Ruggeri, R.M.; Guzzo, E.; Certo, R.; Alibrandi, A.; Scifo, S.; Scardigno, M.; Vitarelli, E.; Arena, G.; Gambadoro, O.; Catalano, N.; Bourdon, J.C.; Galletti, B.; Galletti, F.; Cavallari, V.
    Background. P53, a crucial suppressor of tumor formation, generates multiple isoforms, whose role in disease is still being defined. Methods. By immunohistochemistry, we studied the expression of P53 protein and relative isoforms in benign papillomas (PA, n=9), inverted papilloma (IPA, n=10) and squamous cell carcinomas (SCC, n=21). Results. In all lesions, P53 isoforms were significantly more expressed than P53. Immunoexpression of P53 matched with P53 isoforms in IPA as well as in SCC. Simultaneous immunoexpression of P53 and related isoforms was double in SCC compared to IPA (10% vs 24%), while expression of P53 isoforms was strongly reduced (70% vs 43%). IPA showed the highest percentage of both reactive cases and immunostained cells expressing P53 isoforms. Conclusions. We found the higher expression of P53 isoforms in IPA and SCC compared to PA, suggesting their role in local aggressiveness and malignant proliferation in head-neck lesions.
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    Immunoreactions for P53 isoforms are associated with ultrastructural proliferative profiles in benign thyroid nodules
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Concetta Trovato, Maria; Ruggeri, Rosaria Maddalena; Scardigno, Marco; Sturniolo, Giacomo; Vita, Roberto; Vitarelli, Enrica; Arena, Grazia; Gambadoro, Orazio; Sturniolo, Giovanni; Trimarchi, Francesco; Benvenga, Salvatore; Bourdon, Jean-Christophe; Cavallari, Vittorio
    Background: P53 isoforms originate from the alternative initiation of P53 gene translation through usage of an internal promoter located in intron 4. All P53 isoforms are spliced in intron 9 and may modulate cell proliferation and cell fate outcome in response to DNA damage. Aim: To examine immunoexpression of P53 isoforms in benign proliferative lesions occurring in multinodular thyroids and to assess the ultrastructural phenotype of P53 distribution in the thyrocytes of those lesions by electron microscopy. Materials and Methods: By immunohistochemistry and transmission electron microscopy (TEM), we evaluated 38 multinodular thyroids containing a total of 102 benign lesions: 38 nodular goiters (NG; colloid=20, parenchymatous=18), 52 follicular adenomas (FA) and 12 Hashimoto’s thyroditis (HT). FA were classified into 10 normo-follicular, 9 macro-follicular, 28 microfollicular and 5 solid variants. Results: Immunoreaction for P53 isoforms was observed in approximately 50% of all lesions, except macrofollicular variant FA (33%). At TEM analysis, immunoreactive NG, FA and TH lesions showed signs of proliferation by simultaneous appearance of dispersed chromatin, increased amounts of cytoplasmic organelles and dilation of the rough endoplasmic reticulum. TEM signs of apoptosis and proliferation were also detected in FA, but with different rates compared to NG. Conclusion: The immunohistochemical expression of P53 isoforms in NG, FA and HT suggests their role in the development of these lesions. Ultrastructural findings support the hypothesis that P53 immunoexpression correlates with reactive proliferative changes in thyrocytes.
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    Mutant pattern of p53 predicts local recurrence and poor survival rate in gastric cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Chung, Yumin; Lee, Hyoun Wook; Park, Jung Ho; Yoo, Chang Hak; Son, Byung Ho; Kim, Kyungeun
    Background. TP53 mutation is a poor prognostic factor for various organ malignancies such as colorectal cancer, breast cancer, ovarian cancer, hepatocellular carcinoma, lung adenocarcinoma and clinical pathologists previously evaluated it using immunohistochemistry for p53. The clinicopathologic significance of p53 expression in gastric cancer remains unclear due to inconsistent classification methods. Methods. Immunohistochemistry for p53 protein was performed using tissue microarray blocks generated from 725 cases of gastric cancer, and p53 expression was divided into three staining patterns using a semiquantitative ternary classifier: heterogeneous (wild type), overexpression, and absence (mutant pattern). Results. Mutant pattern of p53 expression had a male predominance, greater frequency in cardia/fundus, higher pT stage, frequent lymph node metastasis, local recurrence clinically, and more differentiated histology microscopically compared with wild type. In survival analysis, p53 mutant pattern was associated with worse recurrent-free survival and overall survival rates, and significance was maintained in subgroup analysis of early versus advanced gastric cancers. In Cox regression analysis, p53 mutant pattern was a significant predicting factor for local recurrence (relative risk (RR=4.882, p<0.001)) and overall survival (RR=2.040, p=0.007). The p53 mutant pattern remained significant for local recurrence (RR=2.934, p=0.018) in multivariate analyses. Conclusions. Mutant p53 pattern on immunohistochemistry was a significant prognostic factor for local recurrence and poor overall survival in gastric cancer.