RESUMEN
During the progression of head and neck squamous cell carcinoma (HNSCC), the induction of an epithelial-mesenchymal transition (EMT) program may play a critical role in the dissemination of cells from the primary tumor to distant metastatic foci. The process of EMT involves the activation of several important genes and pathways to help maintain survival and growth and evolve into highly invasive and metastatic variants. In this study, expression microarray analysis identified a set of 145 upregulated genes in EMT-like HNSCC cells. Some of the strongly upregulated transcripts include genes that are reportedly involved in invasion and metastasis, such as DOCK10, LOX, ROBO1 and SRGN. Importantly, the Tbx3 gene, a member of the T-box transcription factor, was strongly upregulated in SCC cells displaying an EMT-like phenotype compared to cells with an epitheloid, non-EMT behavior. Tbx3 was also found to be strongly upregulated at the protein and gene expression level in an experimental model of snail-induced EMT cells. In addition, siRNA-induced Tbx3 depletion modestly suppressed cell invasion while enhancing Tbx3-mediated resistance to anoikis. Our findings provide evidence that Tbx3 overexpression promotes SCC cell survival displaying an EMT phenotype. This set of newly identified genes that are modulated during EMT-like conversion may be important diagnostic biomarkers during the process of HNSCC progression.
Asunto(s)
Carcinoma de Células Escamosas/genética , Transición Epitelial-Mesenquimal/genética , Perfilación de la Expresión Génica , Genes Relacionados con las Neoplasias , Neoplasias de Cabeza y Cuello/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Supervivencia Celular/genética , Transformación Celular Neoplásica/genética , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Genes Relacionados con las Neoplasias/genética , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Humanos , Análisis por Micromatrices , Invasividad Neoplásica , Carcinoma de Células Escamosas de Cabeza y Cuello , Proteínas de Dominio T Box/antagonistas & inhibidores , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Transcripción Genética/fisiología , Regulación hacia Arriba , Estudios de Validación como AsuntoRESUMEN
An unusual thymic carcinoma in a 74-year-old woman is described. Initial chest CT revealed a mass at the mid-posterior mediastinum. Transbronchial fine needle biopsy of the mass failed to provide a definite diagnosis. The mass was treated as a malignant mediastinal tumour, and chemoradiotherapy was performed as initial treatment. The patient died 5 years after receiving primary treatment. The results of postmortem microscopic examination, including immunohistochemical study with CD5 antibody, were consistent with thymic carcinoma. This case is interesting in that the mid-posterior mediastinum is the site where thymic carcinoma is least likely to originate.
Asunto(s)
Coristoma/patología , Enfermedades Linfáticas/patología , Neoplasias del Mediastino/patología , Timoma/patología , Timo , Anciano , Femenino , HumanosRESUMEN
Oral squamous cell carcinoma (OSCC) cells can invade adjacent tissues and the vascular system at an early stage of tumor progression. In the present study, we have attempted to detect circulating cancer cells. We used human OSCC cells expressing green fluorescent protein (GFP) in an orthotopic nude mouse model and were able to detect GFP-expressing cells using a fluorescence activated cell sorter and fluorescence microscopy. We also detected the expression of GFP, squamous cell carcinoma antigen (SCCA), or epidermal growth factor receptor (EGFR) mRNA in the blood of tumor-bearing mice by conventional reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR (TaqMan RT-PCR). TaqMan RT-PCR was the more sensitive method to detect the circulating cancer cells. Furthermore, we examined the expression of SCCA and EGFR mRNA in the peripheral blood of patients with OSCC by conventional RT-PCR and TaqMan RT-PCR. We detected SCCA and EGFR mRNA in few cases by conventional RT-PCR, whereas TaqMan RT-PCR showed their expression in about 50% of cases. However, there was no correlation between detection of circulating viable cancer cells and metastasis to lymph nodes and distant organs. These results suggest that TaqMan RT-PCR is a very useful method and both SCCA and EGFR mRNA may be available as a marker for detection of circulating cancer cells.
Asunto(s)
Carcinoma de Células Escamosas/sangre , Neoplasias de la Boca/sangre , Neoplasias de la Boca/metabolismo , Células Neoplásicas Circulantes/metabolismo , Animales , Línea Celular Tumoral , Progresión de la Enfermedad , Receptores ErbB/metabolismo , Femenino , Citometría de Flujo , Proteínas Fluorescentes Verdes , Humanos , Proteínas Luminiscentes/metabolismo , Metástasis Linfática , Ratones , Ratones Desnudos , Microscopía Fluorescente , Metástasis de la Neoplasia , ARN Mensajero/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
PRPK (p53-related protein kinase) has been reported as a novel protein kinase which binds to the tumor suppressor protein p53 and induces phosphorylation of p53 at Ser 15. To identify novel binding partners of PRPK, we performed a yeast two-hybrid screening and isolated an expressed sequence tag CGI-121 by which a 20-kDa protein was encoded. We demonstrated the protein-protein interaction of CGI-121 with PRPK in vivo and in vitro. The protein expression of CGI-121 was observed in many cell lines and was immunocytochemically identified in both the nucleus and cytosol. Although PRPK interacted with both CGI-121 and p53, several attempts to demonstrate an association between CGI-121 and p53 were unsuccessful. In addition, coprecipitation of p53 using recombinant PRPK was inhibited by adding recombinant CGI-121 in vitro, suggesting that CGI-121 could act as a potent inhibitor of the binding of PRPK to p53.