| Project/Area Number |
11670191
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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 |
Human pathology
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| Research Institution | Kitasato University |
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Principal Investigator |
DOBASHI Yoh Kitasato Univ. School of Medicine, Associate Professor, 医学部, 助教授 (90231456)
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| Co-Investigator(Kenkyū-buntansha) |
JIANG Shi-xu Kitasato Univ. School of Medicine, Assistant Professor, 医学部, 講師 (70276153)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | cell cycle / cyclin / cdk / lung cancer / cdc2 / apoptosis / アポトーシス / cyclin / cdk |
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| Research Abstract |
To investigate the abnomatily of cell cycle regulation and its clinical application in human lung cancer, we performed 1) immunohistochemical staining with subsequent clinicopathological analysis on the surgical materials of lung cancer, 2) cell biological analysis using cultured cell lines of human lung cancer.
1-I) expression of cyclin A serves as a marker of proliferative activity and patients' poor prognosis, ii) this was also true in sarcomoa, iii) cyclin E positivity also indicates worse prognosis in adenocarcinoma, but better prognosis in squamous cell carcinoma (SCC), iv) positivity of cyclin E in SCC reflects accumulation of protein in non-proliferating cells and may result from the downregulation of cyclin E degradation, iv) cdk-inhibitor serve as a assmbly factor for cyclin/cdk in low dose and activate its complex.
2-I) Two cell lines of large cell carcinoma and 3 lines of small cell carcinoma were established from surgical materials, ii) overexpression of cdc2 or cdk2 suppressed differentiation of PC12 cells, iii) that simultaneous downregulation of cdc2 and cdk2 activity induces neuronal differentiation in PC12 cells iv) overexpression of cdk4 induced apoptosis in all cell lines of lung carcinoma.
The results described in 1 showed diversity in the expression mechanism of cell cycle molecules depending on the histological type and utility of immunostaining of those protein for the evaluation of patients' prognosis in lung cancer. The results of 2 shed the light on the new mode of therapy for lung cancer by inducing apoptosis of cellular differentiation with administration of cell cycle molecules.
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