| Project/Area Number |
16390576
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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 |
TOTSUKA Yasunori Hokkaido University, Graduate School of Dental Medicine, Professor, 大学院・歯学研究科, 教授 (00109456)
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| Co-Investigator(Kenkyū-buntansha) |
SHINDOH Masanobu Hokkaido University, Graduate School of Dental Medicine, Professor, 大学院・歯学研究科, 教授 (20162802)
KOBAYASHI Masanobu Hokkaido University, Institute for Genetic Medicine, Associate Professor, 遺伝子病制御研究所, 助教授 (80241321)
HIGASHINO Fumihiro Hokkaido University, Graduate School of Dental Medicine, Instructor, 大学院・歯学研究科, 助手 (50301891)
OHIRO Yoichi Hokkaido University Hospital, Instructor, 助手 (40301915)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2005: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥11,600,000 (Direct Cost: ¥11,600,000)
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| Keywords | Oral carcinoma / DNA microarray / Chemo- and radio- sensitivity / Bcl-2 family / p53 / VEGF-C / Bcl-2 / 口腔扁平上皮がん / リンパ節転移 / real-time RT-PCR |
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| Research Abstract |
E1AF is an ets-oncogene family transcription factor and it has been shown to upregulate multiple MMPs whereas MMP-2, a potent extracellular matrix degrading enzyme, is not upregulated. Chloramphenicol acetyltransferase (CAT) assay was utilized to investigate whether E1AF is able to upregulate MT1-MMP, which is known to activate MMP-2. Expression of the CAT reporter gene under the control of the MT1-MMP promoter was increased approximately 40-fold by co-transfection with the E1AF expression vector. Real-time RT-PCR study was carried out in 25 patients with tongue squamous cell carcinoma, and the mRNA expression level of E1AF,MT1-MMP was synergistically increased.
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 the relationship between Bcl-2 family gene expression and the effect of chemo- and rad
… More
iotherapy. Bax was shown to reduce the expression in all carcinoma cases. High expression levels of Bcl-2 were observed in resistant cases for chemo- and radiotherapy. These results suggest that examination of Bcl-2 family gene expression levels would be the predictive factors of sensitivity for preoperative therapies.
Ets-1,Ets-2, and GnT-V mRNA expression were analyzed by the reverse transcription-polymerase chain reaction method in biopsy materials of 19 SCC cases and 4 premalignant lesions and compared with the expression levels of normal tongue tissues. Immunohistochemical detection of GnT-V and the relationship between clinico-pathological features were investigated. All premalignant lesions and SCC cases examined showed significantly escalated Ets-1 mRNA levels compered with normal tongue tissues by real-time PCR. Ets-2 and GnT-V mRNAs levels were also increased in SCC cases, but in contrast, their levels were not enhanced in premalignant lesions in comparison to normal tissues. The levels of GnT-V mRNA were correlated with Ets-1 and Ets-2 expression (rs=0.7;p<0.01). Ets-1 and GnT-V expression in SCC were positively associated with the tumor invasive pattern and cervical lymph node metastasis. On the contrary, Ets-2 expression has little relationship with these characteristics. These results suggest that Ets-1 plays a significant role in regulating GnT-V in human tongue squamous cell carcinoma and might be involved in the potential for malignancy via the action of GnT-V. Less
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