Analysis of DNAdamage checkpoint regulator gene and cancer control mechanism in oral cancer

口腔癌DNA损伤检查点调节基因及控癌机制分析

• 批准号: 17591923
• 负责人: KOHNO Yohko
• 金额: $ 2.33万
• 依托单位: Showa 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 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591923/
• 关键词: Oral cancer; DNA damage; p53; Tumor suppressor gene

Damage and abnormality of DNA genome is the starting point of the process of malignant transformation of a normal cell. Once DNA damage occurs, eukaryotic cells can activate cell cycle checkpoints, apoptosis or senescence. Some kinases are related to cell cycle checkpoint, apoptosis and senescence pathways, and stimulate and activate other kinases. p53, a transcriptional factor mutated in over 50% of human cancers, is phosphorylated at Ser15 and Ser37 by ATM/ATR and DNA-PK. This phosphorylation promotes the accumulation and functional activation of p53 in response to DNA damage. Active Chk1 and Chk2 can phosphorylate p53 at several serine : sites, enhancing its tetramerization, stability and activity. In 60% of oral cancer, p53 is mutated. It seems that some kinds of oral cancer have different signal transmission pathways which are regarded as conventional DNA damage signal transmission pathways. We used several kinds of oral squamous carcinoma cell lines to check the expression of p53 first. After treatment with genotoxic stress to culture cells, we examined the expression of each protein in DNA damage checkpoint by Western blot analysis, and checked the localization in oral mucosal tissues by immunohistochemistry.

DNA基因组的损伤和异常是正常细胞恶变过程的起点。一旦DNA损伤发生，真核细胞可以激活细胞周期检查点、凋亡或衰老。一些激酶与细胞周期检查点、细胞凋亡和衰老途径有关，并能刺激和激活其他的激酶。P53是一种转录因子，在超过50%的人类癌症中发生突变，通过ATM/ATR和DNA-PK在Ser15和Ser37处被磷酸化。这种磷酸化促进了P53的积聚和功能激活，以应对DNA损伤。活性Chk1和Chk2可以在多个丝氨酸位点磷酸化P53，增强其四聚化、稳定性和活性。在60%的口腔癌中，P53发生了突变。一些口腔癌似乎有不同的信号传递途径，被认为是传统的DNA损伤信号传递途径。我们首先用几种口腔鳞癌细胞系检测了P53的表达。培养细胞经基因毒性应激处理后，用Western印迹法检测各蛋白在DNA损伤检查点的表达，用免疫组织化学方法检测各蛋白在口腔黏膜组织中的定位。

项目成果

Inhibition of connexin43 in cultured dental pulp by antisense oligonucleotides

反义寡核苷酸对培养牙髓中连接蛋白43的抑制作用

• 发表时间: 2007
• 期刊: Cell & Tissue Research 329(2)
• 作者: Chung;CK;Muramatsu;T;Uekusa;T;Sasaki;H;Shimono;M
• 通讯作者: M

Uni-axial stretching regulates intracellular localization of Hic-5 expressed in smooth-muscle cells in vivo

• DOI: 10.1242/jcs.01683
• 发表时间: 2005-03-01
• 期刊: JOURNAL OF CELL SCIENCE
• 影响因子: 4
• 作者: Kim-Kaneyama, J;Suzuki, W;Shibanuma, M
• 通讯作者: Shibanuma, M

Inhibition of connexin43 in cultured dental pulp by antisense oligonucle otides

反义寡核苷酸对培养牙髓中连接蛋白43的抑制作用

• 发表时间: 2007
• 期刊: Cell&Tissue Research 329
• 作者: Lee;MK;Muramatsu;T;Uekusa;T;Lee;JH;Shimono;M;Chung CK.
• 通讯作者: Chung CK.

Microarray Analysis on Odontogenesis-related -genes in Mouse Dental Papillae

小鼠牙乳头成牙相关基因的微阵列分析

• 发表时间: 2005
• 期刊: J Hard Tissue Biol 14(2)
• 作者: Muramatsu;T;Sasaki;H;Yamamoto;H;Kohno;Y;Cho;SW;Jung;FS;Shimono;M
• 通讯作者: M

A case of clear cell variant of mucoepidermoid carcinoma with oncocytic metaplasia The Korean Journal of Oral and Maxillofacial Pathology 29(2) : 167, 2005

粘液表皮样癌透明细胞变型伴嗜酸细胞化生一例 The Korean Journal of Oral and Maxillofacial Pathology 29(2) : 167, 2005

• 作者: Muramatsu;T;H.;ashimono;S;Inoue;T;Ogawa;I;Takata;T;Shimono;M
• 通讯作者: M