Prediction of malignant transformation of oral precancerous lesions by analyzing gene expression profiles and gene polymorphism.

通过分析基因表达谱和基因多态性预测口腔癌前病变恶变。

基本信息

批准号：
15209070
负责人：
NAGUMO Masao
金额：
$ 25.71万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

To basically investigate changes in gene expression profiles during carcinogenesis, changes in gene expression profiles and morphological changes were examined in the tongue epithelial tissues of the mice after administrating carcinogens, 4NQO or benzo 【a】 pyrene. Further gene expression profiles were compared among human normal epithelia, oral leukoplakias and oral cancers using GeneChip system, and as to markedly up-regulated genes, their protein expression in those tissues was examined immunohistochemically.The results obtained were as follows :1) Epithelial dysplasia was observed in the tongue epithelia at 6 weeks after administration of carcinogens.2) Expression of 63 genes was up-regulated, while that of 6 genes was down-regulated by the administration of carcinogens. Especially, characteristic changes were observed in SPRR2A, SPRR2E, SPRR2B and SPRR3 genes. Of these genes up-regulation of SPRR2A mRNA was confirmed by RT-PCR method.3) In oral leukoplakia, 8 genes were up-regulated and 10 genes were down-regulated when compared with normal epithelial tissues. Of these genes, loricrin, keratin 2E and keratin10 genes were markedly down-regulated in oral cancer tissues.4) In cases developing cancers from oral leukoplakias, gene expression in cancer tissues of loricrin, karatin10 and kallikrein was markedly down-regulated in comparison with oral leukoplakias.5) Immunohistochemical examination revealed that expression of keratin10 protein was markedly decreased and it was only localized at the center of cancer lobules.6) Kallikrein protein was also slightly localized at the center of cancer lobules.These results indicates that changes in loricrin, karatin10 and kallikrein may be predictive markers of malignant transformation from oral leukoplakia. Analysis of gene polymorphism (SNP) is now undergoing and SNPs responsible for malignant transformation were not yet determined.

为了基本研究致癌过程中基因表达谱的变化，在给予致癌物质、4NQO或苯并[a]芘后，检查了小鼠舌上皮组织中基因表达谱的变化和形态学变化，并与正常人进行了进一步的基因表达谱的比较。利用GeneChip系统对上皮细胞、口腔白斑和口腔癌进行检测，对于显着上调的基因，通过免疫组化方法检测其在这些组织中的蛋白表达。结果如下：1）给予致癌物质后6周，舌上皮细胞出现上皮发育不良。2）给予致癌物质后，63个基因表达上调，6个基因表达下调。特别是，通过RT-PCR方法证实了SPRR2A、SPRR2E、SPRR2B和SPRR3基因的特征性变化。3)在这些基因中SPRR2A mRNA的上调。口腔白斑中，与正常上皮组织相比，有8个基因上调，10个基因下调，其中兜甲蛋白、角蛋白2E和角蛋白10基因在口腔癌组织中显着下调。4)在发生癌症的情况下。与口腔白斑相比，癌组织中loricrin、karatin10和激肽释放酶的基因表达显着下调5) 免疫组织化学检查显示，keratin10蛋白的表达明显降低，仅位于癌小叶的中心。6) Kallikrein蛋白也轻微位于癌小叶的中心。这些结果表明，兜甲蛋白的变化， karatin10 和激肽释放酶可能是口腔白斑恶变的预测标志物。基因多态性 (SNP) 分析是。目前正在发生，并且导致恶性转化的 SNP 尚未确定。

项目成果

期刊论文数量（64）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Selective COX-2 inhibition suppresses invasiveness of oral squamous cell carcinoma cells through down-regulation of MMP-9.

选择性 COX-2 抑制通过下调 MMP-9 抑制口腔鳞状细胞癌细胞的侵袭性。

DOI：
发表时间：
期刊：
J Showa Univ Dent Socie (in press)
影响因子：
0
作者：
Yoshimura;S. and Kawai;N.;山下(高橋)則子;Saito M et al.
通讯作者：
Saito M et al.

Gene expression profiles of oral leukoplakia and carcinoma : Genome-wide comparison analysis using oligonucleotide microarray

口腔白斑和癌的基因表达谱：使用寡核苷酸微阵列进行全基因组比较分析

DOI：
发表时间：
2006
期刊：
Int J Oncology 28(3)
影响因子：
0
作者：
YOSHIOKA Takatomo;HANADA Takahiro;KAWAMURA Yoko;OKITSU Motoko;SUDA Hideaki;Odani T et al.
通讯作者：
Odani T et al.

Enhancement of susceptibility to Fas-mediated apoptosis in oral squamous cell carcinoma cells by phosphatidylinositol 3-kinase inhibitor.

磷脂酰肌醇 3-激酶抑制剂增强口腔鳞状细胞癌细胞对 Fas 介导的细胞凋亡的敏感性。

DOI：
发表时间：
2006
期刊：
Oral Oncology (in press)
影响因子：
0
作者：
Maruoka R;Nikaido T;Ikeda M;Ishizuka T;Foxton RF;Tagami J;Kondo et al.
通讯作者：
Kondo et al.

Alterrations in G1 phase cell cycle regulation during the Development of benzo 【a】 pyrene induced epithelial dysplasia in the murine tongue.

苯并[a]芘发育过程中G1期细胞周期调节的改变引起小鼠舌头上皮发育不良。

DOI：
发表时间：
2004
期刊：
Oral Science International 1(2)
影响因子：
0
作者：
Hirotoshi Akigawa;Toru Nikaido;Michael F.Burrow;Junji Tagami;Sanada M et al.
通讯作者：
Sanada M et al.

Thalidomide suppresses melanoma growth by activating natural killer cells in mice.