| Project/Area Number |
14370654
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
SHINDOH Masanobu Hokkaido Univ., Grad.Sch.of Dent.Med., Prof., 大学院・歯学研究科, 助教授 (20162802)
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| Co-Investigator(Kenkyū-buntansha) |
OHIRO Yoichi Hokkaido Univ., Med.&Dent.Hospital, Asso.Prof., 医学部・歯学部附属病院, 助手 (40301915)
HIGASHINO Fumihiro Hokkaido Univ., Grad.Sch.of Dent.Med., Inst., 大学院・歯学研究科, 助手 (50301891)
KOBAYASHI Masanobu Hokkaido Univ., Inst.Genet.Med., Asso.Prof., 遺伝子病制御研究所, 助教授 (80241321)
TOTSUKA Yasunori Hokkaido Univ., Grad.Sch.of Dent.Med., Prof., 大学院・歯学研究科, 教授 (00109456)
YASUDA Motoaki Hokkaido Univ., Grad.Sch.of Dent.Med., Asso.Prof., 大学院・歯学研究科, 助教授 (90239765)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2003: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2002: ¥10,800,000 (Direct Cost: ¥10,800,000)
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| Keywords | Oral carcinoma / Immortalization / Invasion and metastasis / Protein-protein interaction / Gene therapy / ets oncogene / E1AF / MMP / TIMP / 口腔扁平上皮がん / 浸潤 / 転移 |
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| Research Abstract |
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.
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