2006 Fiscal Year Final Research Report Summary
Study on the abnormal genetic expression involved in de-differentiation of anaplastic thyroid carcinoma
| Project/Area Number |
17591341
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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 |
General surgery
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| Research Institution | Osaka City University |
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Principal Investigator |
ONODA Naoyoshi Osaka City University, Graduate School of Medicine, Lecturer (30295703)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Tetsuro Osaka City University, Graduate School of Medicine, Associate professor (50193280)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Thyroid cancer / anaplastic thyroid cancer / de-differentiation / DNA methylation / p16 gene |
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| Research Abstract |
AIM>
To investigate the possible role of abnormal DNA methylation in the de-differentiation process of the anaplastic thyroid cancer.
MATERIALS>
Five anaplastic thyroid cancer cell lines (ACT-1, KTC-1, TTA-1, OCUT-1, OCUT-2)
METHODS>
DNA methylation of the promoter CpG island was investigated by methylation specific PCR method in the following gene ; p16, E-cadherin, hMLH-1, BRCA-1, and DAP kinase.
Expression of mRNA was investigated by RT-PCR method in the following gene ; TTF-1 and PAX-8
Effect on of the de-methlating agent on the cell viability was determined by MTT assay.
RESULTS>
Expression of p16 gene was altered in every cell lines investigated. ACT-1, OCUT-1 and OCUT-2 showed CpG island methylation. KTC-1 and TTA-1 showed deletion or mutation.
Methylation of the CpG island in E-cadherin gene was found in TTA-1.
No abnormal methylation was found in CpG island of the hMLH-1, BRCA-1, and DAP kinase gene in every cell lines.
Expression of TTF-1 and PAX-8 mRNA did not change by the exposure to the de-methylating agent.
No significant adverse effect of deethylation agent was found on the cell viability
DISCUSSIONS>
Alteration in p16 gene expression was found universally in every anaplastic thyroid cancer cell lines. This down regulation of p16 gene was partly established by DNA methylation of promoter CpG island of the gene. However, DNA methylation itself was not frequent in the cell lines, as demonstrated in the previous reports. Moreover, no adverse effect of de-methylation agent was found on the cell viability, suggesting little involvement of abnormal DNA methylation on de-differentiation process of anaplastic thyroid cancer. Thus, the failure in the cell cycle control might have a major role in the process of de-differentiation of thyroid cancer.
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