Study on the abnormal genetic expression involved in de-differentiation of anaplastic thyroid carcinoma

甲状腺未分化癌去分化异常基因表达的研究

• 批准号: 17591341
• 负责人: ONODA Naoyoshi
• 金额: $ 1.34万
• 依托单位: Osaka City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591341/
• 关键词: Thyroid cancer; anaplastic thyroid cancer; de-differentiation; DNA methylation; p16 gene; 染色体不安定性; 遺伝子不安定性

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-8Effect 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 viabilityDISCUSSIONS>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.

目的>探讨异常DNA甲基化在甲状腺未分化癌去分化过程中的可能作用。材料>5种甲状腺未分化癌细胞系（ACT-1、KTC-1、TTA-1、OCUT-1、OCUT- 2)方法>采用甲基化特异性PCR方法检测下列基因启动子CpG岛的DNA甲基化情况； p16、E-钙粘蛋白、hMLH-1、BRCA-1和DAP激酶。通过RT-PCR方法研究以下基因中mRNA的表达； TTF-1和PAX-8通过MTT法测定去甲基化剂对细胞活力的影响。结果>在所研究的每个细胞系中p16基因的表达发生改变。 ACT-1、OCUT-1 和 OCUT-2 显示 CpG 岛甲基化。 KTC-1和TTA-1出现缺失或突变。TTA-1中发现E-cadherin基因CpG岛甲基化。hMLH-1、BRCA-1和DAP激酶的CpG岛未发现异常甲基化每个细胞系中都有基因。TTF-1和PAX-8 mRNA的表达没有因暴露于去甲基化剂而改变。未发现去乙基化剂对细胞有明显的不利影响活力讨论>p16 基因表达的改变在每种未分化甲状腺癌细胞系中都普遍存在。 p16 基因的这种下调部分是由该基因的启动子 CpG 岛的 DNA 甲基化建立的。然而，正如之前的报告所证明的那样，DNA 甲基化本身在细胞系中并不常见。此外，未发现去甲基化剂对细胞活力产生不利影响，表明异常DNA甲基化对甲状腺未分化癌的去分化过程影响不大。因此，细胞周期控制的失败可能在甲状腺癌去分化过程中发挥重要作用。

项目成果

Helicobacter pylori infection, but not mucosal atrophy, significantly affects serum pepsinogen level after gastric cancer surgery.

幽门螺杆菌感染显着影响胃癌术后血清胃蛋白酶原水平，但不影响粘膜萎缩。

• 发表时间: 2006
• 期刊: Hepatogastroenterology. Jul-Aug;53(70)
• 作者: Onoda N;Katsuragi K;Maeda K;Sawada T;Wakasa K;Hirakawa K.
• 通讯作者: Hirakawa K.

Specific subtelomere loss on chromosome der(11)t(3;11)(q23;q23)xII in anaplastic thyroid cancer cell line OCUT-1.

间变性甲状腺癌细胞系 OCUT-1 中染色体 der(11)t(3;11)(q23;q23)xII 上的特定亚端粒丢失。

• 发表时间: 2006
• 期刊: Int J Mol Med. Jul;18(1)
• 作者: Kammori M;Onoda N;Nakamura K;Izumiyama N;Ogisawa K;Kurabayashi R;Ogawa T;Kaminishi M;Poon SS;Takubo K.
• 通讯作者: Takubo K.

Frequent p16 CpG island hypermethylation in primary remnant gastric cancer suggesting an independent carcinogenic pathway.

• DOI: 10.3892/or.15.3.615
• 发表时间: 2006-03
• 期刊: Oncology reports
• 影响因子: 4.2
• 作者: A. Mino;N. Onoda;M. Yashiro;M. Aya;Ichiro Fujiwara;N. Kubo;T. Sawada;M. Ohira;Y. Kato