| Project/Area Number |
14570454
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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 |
Gastroenterology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
IMOTO Issei Tokyo Medical and Dental University, Medical Research Institute, Associate Professor, 難治疾患研究所, 助教授 (30258610)
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| Co-Investigator(Kenkyū-buntansha) |
INAZAWA Johji Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究, 教授 (30193551)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Apoptosis / cIAP1 / Esophageal Cancer / Cervical Cancer |
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| Research Abstract |
Recently we reported that cIAP1, an inhibitor of apoptosis, is overexpressed through 11q22 amplification in cell lines derived from esophageal squamous cell carcinomas and is associated with resistance of esophageal squamous cell carcinomas to drug-induced apoptosis.
(1) Because amplification of 11q22 has been implicated in other malignancies also, including cervical squamous cell carcinomas (CSCCs), we attempted to correlate amplification and overexpression of cIAP1 with radiation sensitivity in CSCC-derived cell lines and primary CSCC tumors. CSCC cell lines with amplification and consistent overexpression of cIAP1 showed significant resistance to radiation-induced cell death as compared with lines without cIAP1 amplification. Immunohistochemical analysis of 70 primary CSCCs from patients treated only with radiotherapy demonstrated that both overall survival and local recurrence-free survival was significantly poorer among patients with tumors showing high levels of nuclear cIAP1 staining than among patients whose tumors revealed little or no nuclear cIAP1. Multivanate analysis showed nuclear cIAP1 staining to be an independent predictive factor for local recurrence-free survival after radiotherapy among patients with CSCC.
(2) In order to identify molecules, which interact with cIAP1, we performed bacterial and yeast two-hybrid screening. Although we identified one mitochondrial protein as candidate, we failed to validate the interaction between those two molecules in vivo. We will try to identify other molecules using immunopreapitation and TOF-MS system. We are also analyzing the effect of down-regulation of cIAP1 on spontaneous and drug-induced apoptosis in cells with overexpression of this protein using siRNA technique
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