| Project/Area Number |
09672032
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 of Education |
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Principal Investigator |
ISOGAI Hiroshi Hokkaido University of Education, Dept of Education, Sapporo Campus, Associate Professor, 教育学部・札幌校, 助教授 (50237674)
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| Co-Investigator(Kenkyū-buntansha) |
FUJINAGA Kei Sapporo Medical University, Dept. of Medicine, Professor emeritus, 付属がん研究所, 名誉教授 (10045338)
ODAJIMA Tetsuyo Sapporo Medical University, Dept. of Medicine, Assistant Professor, 医学部, 講師 (00177239)
ISOGAI Hiroshi Sapporo Medical University, Dept. of Medicine, Associate Professor, 医学部, 助教授 (50137436)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | E1AF / polyclonal antibody / transcriptional factor / metastasis / invasion / oral cancer / prognosis / MMP / 浸潤 / 予後 / EIAF / ポリフロナール抗体 / ウエスタンブロット法 / 癌細胞株 / RNA / 癌 / ets癌遺伝子 / レトロウイルスベクター / uPA |
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| Research Abstract |
It is assumed that decomposing matrix outside the cell is necessary for the metastasis of the cancer cells, and the expression of the matrix metaroprotease (henceforth MMP) is important for it. It had been reported that the ETS binding domein was located in the transcriptional regulation area in the upstream of these genes, and which played an important role in the transcriptional regulation of these genes by binding of ets-oncogene family products.
The protein was extracted from oral malignant tumors (malignant squamous cell carcinoma cell lines), and the expressions of the E1AF protein were studied by the Western-blot analysis. There were some cell lines in which E1AF protein was expressed, but no cell lines of strong protein expression. In other words, there were many cancer cells in which E1AF mRNA was strongly expressed, but no cancer cells of strong protein expression of E1AF. So, we suspected that there was some possibility that the E1AF protein expression was very low or decompo
… More
sed soon because of that low stability in cancer cells. The E1AF gene under the retrovirus enhancer/promoter was transfected into the cancer cells in which E1AF was not expressed, and the producer cell lines were established. The abilities of metastasis and mobility were elevated in the experiment of injecting these cells to nude mouse subcutaneously. These data support the hypothesis that the metastasis and invasion of a malignant tumor had deeply been affected by E1AF gene.
The analysis of the expressions such as the MMP proteins (MMP3 and MMP9 proteins) was also carried at the same time. We investigated the expressions of these genes, the histopathological type of cancer (malignant degree), and the prognosis, and the relation between them was also examined.
It was generally thought that the stronger protein expression of E1AF gene was, the more malignant the cancer was (the worse prognosis was). (The expressions of the MMP proteins such as MM3 and MMP9 protein were also high at the same time), and the expressions of these genes have much relation to the malignant degree of cancer and the metastasis ability in many cases of cancer cell lines. Less
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