1999 Fiscal Year Final Research Report Summary
The functional analysis and clinical application of the metastasis-associated gene TI-241.
| Project/Area Number |
10671159
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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 |
Digestive surgery
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| Research Institution | The University of TOKYO |
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Principal Investigator |
ISHIGURO Tatsuaki The University of TOKYO, Dept. of Surgical Oncology, Assistant Professor, 医学部・附属病院, 助手 (90292945)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAWA Hirokazu The University of TOKYO, Dept. of Surgical Oncology, Professor, 医学部・附属病院, 教授 (80228064)
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| Project Period (FY) |
1998 – 1999
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| Keywords | cancer metastasis / metastasis-associated gene / TI-241 |
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| Research Abstract |
We performed differential screening between melanoma sublines of dirrerent metastatic potentials and isolated several genes that were differentially expressed between them. Most of these genes were already reported, but some were not. In those, TI227 showed no homology with formaly reported genes and differentally expressed in the sublines of colon cancer cells with different metastatic potential. This gene was expressed more in the highly experimentally metastatic subline of colon cancer cells. We analyzed its sequence and isolated its human counterpart TI227H. From the homology research between TI227 and TI227H, the most possible ORF was determined. We further isolated genomic DNA containing TI227 and analysed its 5' upstream sequence. TI227 was expected to be used in the diagnosis of metastatic potential and prognosis. Another gene TI241 showed homology with transcription factors of LRF1 and ATP3. Its transfection to the low metastatic subclone strengthened its metastatic potential and its expression in the metastatic foci was elevated. In the study using surgically excised specimens, its expression was expressed more in the cases with vascular invasions and its importance as a prognosis predictor was expected. Also from the study with the antisense oligonucleotides, TI241 was shown to relate cell adhesion and invasion and was thought to relate in vivo growth. From the exp6riments using nude mice, it surpressed subcutaneus growth and lengthened their survival period, which opened a possibility of its application to the gene therapy. Above results were already published or submitted to the English journals.
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