Research on factors involved in prognosis of oral carcinoma.

EWS/ETS是在大多数尤文肉瘤中鉴定的嵌合蛋白。我们证明，端粒酶是EWS/ETS融合蛋白的一个新靶点。EWS/Ets上调了TERTmRNA的表达;然而，EWS/Ets以不依赖于EBS的方式发挥功能，EWS/ETS融合蛋白作为转录共激活因子激活人端粒酶活性。腺病毒E4 orf 6是一种病毒癌蛋白，并且已显示其抑制p53和p73的凋亡活性。我们证明腺病毒E4 ort 6蛋白直接抑制BNIP 3和Bik介导的凋亡，BNIP 3和Bik是Bcl-2家族的BH 3-only蛋白，并且E4 orf 6从细胞核到细胞质的输出信号被证明对于抑制凋亡活性是重要的。25例舌鳞癌组织中E1 AF和MT 1-MMP的表达呈协同增强。这些结果表明，E1 AF正调控MT 1-MMP基因的转录，其通过转化pro-MMP-2在舌鳞状细胞癌的侵袭和转移中起重要作用。采用实时荧光定量RT-PCR方法检测48例口腔鳞癌组织中VEGF-C mRNA的表达水平。VEGF-C在48例宫颈癌中有20例呈高表达，VEGF-C表达水平与颈淋巴结转移密切相关。提示VEGF-C高表达可作为口腔鳞癌颈淋巴结转移的预测指标，尤其是在早期口腔鳞癌中。

EWS/ETS is a chimeric protein identified in most Ewing's sarcomas. We demonstrate that telomerase is a new target of EWS/ETS fusions TERT mRNA were up-regulated by EWS/Ets ; however, EWS/Ets function in an EBS-independent manner and EWS/ETS fusion proteins were shown to activate human telomerase activity as a transcriptional co-activator. The adenovirus E4orf6 is a viral oncoprotein and it has been shown to inhibit the apoptotic activities of p53 and p73. We demonstrate that the adenovirus E4ort6 protein directly inhibits apoptosis mediated by BNIP3 and Bik, which are BH3-only proteins of the Bcl-2 family and that the export signal of E4orf6 from the nucleus to the cytoplasm was shown to be important for the inhibition of apoptotic activity.We investigated the activation mechanism of MMP-2 in oral squamous cell carcinomas. CAT assay revealed that MT1-MMP promoter was activated by E1AF and Real-time RT-PCR study in 25 patients with tongue squamous cell carcinoma showed synergistical increasing expression of E1AF and MT1-MMP. These results indicate that E1AF positively regulates transcription from MT1-MMP genes, which plays an important role in invasion and metastasis of squamous cell carcinoma of the tongue by converting pro-MMP-2. into active-MMP-2 We investigated expression levels of VEGF-C mRNA in 48 cases of 0SCC by real-time RT-PCR. High levels of VEGF-C expression were identified 20 of 48 cases examined Expression level of VEGF-C was significantly associated with cancer cell metastasis in cervical lymph node. These results suggest that high expression of VEGF-C would be a predictive parameter for cervical lymph node metastasis of 0SCC, especially in the early stage tumors.