| Project/Area Number |
09253256
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
TAKAHASHI Takashi Aichi Cancer Center, Laboratory of Ultrastructure Research, 超微形態学部, 部長 (50231395)
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| Co-Investigator(Kenkyū-buntansha) |
MASUDA Akira Aichi Cancer Center, Laboratory of Ultrastructure Research, 超微形態学部, 主任研究員 (50157202)
OSADA Hirotaka Aichi Cancer Center, Pathophysiology Unit, 病態学研究室, 室長 (30204176)
谷田部 恭 愛知県がんセンター, 研究所, 研究員 (90280809)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥30,000,000 (Direct Cost: ¥30,000,000)
Fiscal Year 1999: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1998: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1997: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | lung cancer / positional cloning / tumor suppressor gene / mitotic checkpoint / metastasis / molecular epidemiology / がん抑制遺伝子 / がん遺伝子 |
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| Research Abstract |
In the present study, we investigated various aspects of the molecular pathogenesis of human lung cancers. Consequently, the following results were obtained.
(1) Identification of genes involved in the pathogenesis of lung cancers.
We identified a homozygous deletion within a commonly deleted region at 17p 13.3, suggesting the presence of a putative tumor suppressor gene in this particular genomic region. The identified homozygously deleted region was covered by YACs and BACs. To date, a G2 checkpoint-related gene has been identified and is being examined for the presence of mutations in lung cancers.
The other issue investigated in the present study was "mitotic checkpoint". We found that mitotic checkpoint impairment is present in up to 40% of lung cancer cell lines. Furthermore, MAD 1 mitotic checkpoint gene was found to be mutated in lung cancers, although at low frequency.
(2) Novel metastasis related gene, CASPIN/PEDF.
Functional role of a novel serpin gene, CASPIN/PEDF, was investigated in relation to metastasis. Introduction of human CASPIN/PEDF cDNA into a highly metastatic lung cancer line, H460Lu was found to reduce hematogenous metastases to the lung, showing its potency in the repression of metastasis. Together with its chromosomal assignment to 17p 13.3, this finding warrants further investigation of its involvement in the progression of lung cancers.
(3) Molecular epidemiological analyses.
Molecular epidemiological studies were conducted to examine possible relationship of genetic polymorphisms of the glutathione peroxydase and dopamine D4 receptor (DRD4) genes with risk for the acquisition of smoking behavior or the occurrence of lung cancer. We, however, found no significant correlations between genotypes and risk for smoking behavior or lung cancer occurrence.
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