RESUMEN
Inhibitor of growth 4 (ING-4) is a tumor suppressor gene that interacts with nuclear factor-kappaB (NF-kappaB) and represses its transcriptional activity. Several lines of evidence suggest that the tumor suppressor gene ING-4, the transcription factor NF-kappaB and its target genes matrix metalloproteases MMP-2, MMP-9 and urokinase plasminogen activator (u-PA) are critically involved in tumor invasion. The aim of the present study was to investigate immunohistochemically the expression pattern of ING-4, NF-kappaB and the NF-kappaB downstream targets MMP-2, MMP-9 and u-PA in human astrocytomas from 101 patients. We found that ING-4 expression was significantly decreased in astrocytomas, and ING-4 loss was associated with tumor grade progression. Expression of p65, a NF-kappaB subunit, was significantly higher in grade IV than in grade III and grade I/II tumors, and a statistical significant negative correlation between expression of ING-4 and expression of nuclear p65 was noticed. MMP-9, MMP-2 and u-PA were overexpressed in human astrocytomas. Of note, astrocytomas of advanced histologic grades (grade III, IV) displayed significantly higher expression levels of these proteins compared to tumors of lower grades (grade I, II). Collectively, our data suggest an essential role for ING-4 in human astrocytoma development and progression possibly through regulation of the NF-kappaB-dependent expression of genes involved in tumor invasion.
Asunto(s)
Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Homeodominio/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Astrocitoma/genética , Astrocitoma/patología , Encéfalo/metabolismo , Encéfalo/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Proteínas de Ciclo Celular/genética , Núcleo Celular/metabolismo , Niño , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Proteínas de Homeodominio/genética , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , FN-kappa B/metabolismo , Proteínas Supresoras de Tumor/deficiencia , Proteínas Supresoras de Tumor/genética , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Adulto JovenRESUMEN
p53 protein promotes apoptosis, whereas Bcl-2 family proteins have an antiapoptotic function. This study determines the predictive value of selected clinical and histopathological factors in correlation with the expression of p53, Bcl-2, and Bcl-X(L) proteins in esophageal squamous cell carcinomas (SCCs). Paraffin-embedded sections from 19 surgically resected primary esophageal SCCs were examined by immunohistochemistry. p53 expression was related to degree of tumor differentiation (P = 0.044). Bcl-2 expression was associated with regional lymph node metastasis (P = 0.053), whereas Bcl-X(L) expression was correlated with distant metastasis (P = 0.060) and with the expression of Bcl-2 protein (P = 0.068). p53 and Bcl-2 family proteins may help to estimate the properties of esophageal SCCs and provide useful information to the oncologist for the selection of patients for intensive combined therapy modalities with curative intention or for palliative therapy.
Asunto(s)
Carcinoma de Células Escamosas/química , Neoplasias Esofágicas/química , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteína p53 Supresora de Tumor/análisis , Proteína bcl-X/análisis , Apoptosis , Carcinoma de Células Escamosas/patología , Diferenciación Celular , Neoplasias Esofágicas/patología , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana EdadRESUMEN
The Fas/FasL system plays an important role in the regulation of tumor apoptosis. This study examined the correlation between the expression levels of Fas and WAF1 with the clinicopathological characteristics of esophageal squamous cell carcinoma (SCC) tumors. Paraffin-embedded sections from 19 surgically resected primary esophageal squamous cell carcinomas were examined by immunohistochemistry. At low expression levels (5% to 24%), a 4-fold higher expression of Fas relative to WAF1 expression was observed. High expression levels (50% to 74%) of Fas were not recorded, whereas such levels of expression for WAF1 were retained in a proportion of cells > 20%. Proteins WAF1 and Fas were both expressed in all lesions of SCCs. Lesions showing high expression levels of WAF1 have a high degree of differentiation, but a sample that expresses WAF1 and belongs to the morphology I category probably has a medium degree of differentiation.
