2005 Fiscal Year Final Research Report Summary
Involvement of Pin1 expression on Wnt pathway activation in radiation-associated thyroid cancer
| Project/Area Number |
16590282
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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 | Nagasaki University |
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Principal Investigator |
NAKASHIMA Masahiro Nagasaki University, Graduate School of Biomedical Sciences, Lecturer, 大学院・医歯薬学総合研究科, 講師 (50284683)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Thyroid cancer / Radiation / Wnt signaling pathway / β-catenin / Cyclin D1 / Pin1 |
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| Research Abstract |
We have previously reported a high prevalence of both aberrant β-catenin and cyclin D1 overexpression in radiation-associated thyroid cancers around the Semipalatinsk nuclear test site and Chernobyl accident-contaminated area. In our recent study, Pin1 expression seems to be closely correlated with the level of cyclin D1 overexpression and aberrant β-catenin expression, while neither mutation of β-catenin gene exon 3 nor APC is identified in papillary thyroid cancers (PTC) from radio-contaminated area. Furthermore, Pin 1 overexpression was confirmed in TPC-1, which is a cell line derived from PTC possessing no mutation in neither β-catenin exon 3 nor APC. Thus, Pin1 may be an important factor in regulating cyclin D1 and β-catenin expressions other than the activation of Wnt signaling pathway during thyroid carcinogenesis.
Points in the present study are as followings :
1 Up-regulation of cyclin D1 expression in thyroid canter by Pin1. : In two thyroid cancer cell lines, such as TPC-1 and ARO, an anaplastic thyroid cancer cell line, the level of cyclin D1 but β-catenin expression was significantly decreased by introduction of short interfering RNA s for Pin1.
2 Involvement of Pin1 in thyroid cellular response to irradiation : Pin1 can activate a role of p53 protein which induces apoptosis in radiation injury. The level of cyclin D1 expression was decreased at 2 hr after 10Gy X-ray irradiation in both TPC-1 (wild type p53) and ARO (mutant p53), while apoptotic cell death was more frequently observed in TPC-1 than ARO. Immunoprecipitation with TPC-1 and ARO demonstrated interactions between Pin1 and activated p53/cyclin D1 in irradiated cells.
In conclusion, Pin1 may be one of positive cell cycle regulators in thyroid cancer via up-regulation of cyclin D1 expression, and involved in cellular response to irradiation, such as apoptosis, by interactions with p53 and cyclin D1.
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Research Products
(12 results)
