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.

为了基本上研究癌变期间基因表达谱的变化，在行政致癌物，4NQO或苯并[A] pyrene后，在小鼠的舌头上皮组织中检查了基因表达谱的变化和形态学变化。比较了人类正常上皮症，口服白细胞和口服癌的进一步基因表达谱，并使用Genephip系统以及明显上调的基因，其在这些组织中的蛋白质表达进行了免疫组织的蛋白质表达，从而在辅导中进行了6周的表达，从而在这些组织中进行了免疫组织的蛋白质表达。被上调，而6个基因中的癌症的给药下调。尤其是在SPRR2A，SPRR2E，SPRR2B和SPRR3基因中观察到的特征变化。在口服白细胞中，通过RT-PCR方法证实了SPRR2A mRNA的这些基因上调中，与正常上皮组织相比，在口服白细胞中上调了8个基因，并下调了10个基因。在这些基因中，在口腔癌组织中明显下调了洛林氏蛋白，角蛋白2e和角蛋白10基因。4）在从口腔白细胞发育的病例中，loricrrin，karatin1010和kallikrein的癌症组织中的基因表达与Oral Leukoplakia的表达相比，该基因表达在癌症组织中表达。5）角蛋白10蛋白明显升级，并且仅位于癌症小叶中心。6）Kallikrein蛋白也略微定位在癌症小叶中心。这些结果表明，Loricrin，Karatin10和Kallikrein的变化可能是口服白细胞转化的恶性转化的预测标记。基因多态性分析（SNP）现在正在进行中，尚未确定负责恶性转化的SNP。

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.